[
{
"uniprot_canonical_ac": "Q9UM73-1",
"uniprot_ac": "Q9UM73",
"uniprot_id": "ALK_HUMAN",
"mass": {
"chemical_mass": 176442.0,
"monoisotopic_mass": 176442.0
},
"refseq": {
"ac": "NP_004295",
"name": "ALK tyrosine kinase receptor isoform 1 precursor",
"summary": "This gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).[provided by RefSeq, Jan 2011].",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
},
"gene_names": [
{
"name": "ALK",
"type": "recommended",
"evidence": [
{
"id": "Q9UM73",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
]
},
{
"name": "ALK1",
"type": "synonym",
"evidence": [
{
"id": "NP_004295",
"database": "RefSeq",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
}
]
},
{
"name": "ALK",
"type": "synonym",
"evidence": [
{
"id": "NP_004295",
"database": "RefSeq",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
}
]
},
{
"name": "CD246",
"type": "synonym",
"evidence": [
{
"id": "NP_004295",
"database": "RefSeq",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
}
]
},
{
"name": "NBLST3",
"type": "synonym",
"evidence": [
{
"id": "NP_004295",
"database": "RefSeq",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
}
]
}
],
"protein_names": [
{
"name": "ALK tyrosine kinase receptor",
"type": "recommended",
"evidence": [
{
"id": "Q9UM73",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73/entry#names_and_taxonomy"
}
]
},
{
"name": "2.7.10.1",
"type": "synonym",
"evidence": [
{
"id": "Q9UM73",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73/entry#names_and_taxonomy"
}
]
},
{
"name": "ALK tyrosine kinase receptor isoform 1 precursor",
"type": "synonym",
"evidence": [
{
"id": "NP_004295",
"database": "RefSeq",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
}
]
},
{
"name": "ALK tyrosine kinase receptor",
"type": "synonym",
"evidence": [
{
"id": "NP_004295",
"database": "RefSeq",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
}
]
},
{
"name": "Anaplastic lymphoma kinase",
"type": "synonym",
"evidence": [
{
"id": "Q9UM73",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73/entry#names_and_taxonomy"
}
]
},
{
"name": "CD246 antigen",
"type": "synonym",
"evidence": [
{
"id": "NP_004295",
"database": "RefSeq",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
}
]
},
{
"name": "anaplastic lymphoma receptor tyrosine kinase",
"type": "synonym",
"evidence": [
{
"id": "NP_004295",
"database": "RefSeq",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
}
]
},
{
"name": "mutant anaplastic lymphoma kinase",
"type": "synonym",
"evidence": [
{
"id": "NP_004295",
"database": "RefSeq",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
}
]
}
],
"function": [
{
"annotation": "Findings suggest a novel mechanism of oncogene activation in cancer through de novo alternative transcription initiation, such as for ALK",
"evidence": [
{
"database": "RefSeq",
"id": "NP_004295",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
},
{
"database": "PubMed",
"id": "26444240",
"url": "https://glygen.org/publication/PubMed/26444240"
}
]
},
{
"annotation": "Mucinous epidermoid carcinoma of the lung with ALK mutation: Case report and literature review. Review article",
"evidence": [
{
"database": "RefSeq",
"id": "NP_004295",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
},
{
"database": "PubMed",
"id": "39259069",
"url": "https://glygen.org/publication/PubMed/39259069"
}
]
},
{
"annotation": "Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). May function as regulator of gastric epithelial differentiation (By similarity).",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73#function"
},
{
"database": "PubMed",
"id": "16878150",
"url": "https://glygen.org/publication/PubMed/16878150"
},
{
"database": "PubMed",
"id": "17274988",
"url": "https://glygen.org/publication/PubMed/17274988"
},
{
"database": "PubMed",
"id": "15226403",
"url": "https://glygen.org/publication/PubMed/15226403"
},
{
"database": "UniProtKB",
"id": "P97793",
"url": "https://www.uniprot.org/uniprotkb/P97793#function"
},
{
"database": "PubMed",
"id": "16317043",
"url": "https://glygen.org/publication/PubMed/16317043"
},
{
"database": "PubMed",
"id": "34646012",
"url": "https://glygen.org/publication/PubMed/34646012"
},
{
"database": "PubMed",
"id": "11278720",
"url": "https://glygen.org/publication/PubMed/11278720"
},
{
"database": "PubMed",
"id": "12122009",
"url": "https://glygen.org/publication/PubMed/12122009"
},
{
"database": "PubMed",
"id": "12107166",
"url": "https://glygen.org/publication/PubMed/12107166"
},
{
"database": "PubMed",
"id": "11387242",
"url": "https://glygen.org/publication/PubMed/11387242"
},
{
"database": "PubMed",
"id": "11809760",
"url": "https://glygen.org/publication/PubMed/11809760"
},
{
"database": "PubMed",
"id": "30061385",
"url": "https://glygen.org/publication/PubMed/30061385"
},
{
"database": "PubMed",
"id": "33411331",
"url": "https://glygen.org/publication/PubMed/33411331"
},
{
"database": "PubMed",
"id": "34819673",
"url": "https://glygen.org/publication/PubMed/34819673"
},
{
"database": "PubMed",
"id": "11121404",
"url": "https://glygen.org/publication/PubMed/11121404"
}
]
},
{
"annotation": "Oncogenic EML4-ALK assemblies suppress growth factor perception and modulate drug tolerance. Publication Status: Online-Only",
"evidence": [
{
"database": "RefSeq",
"id": "NP_004295",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
},
{
"database": "PubMed",
"id": "39488530",
"url": "https://glygen.org/publication/PubMed/39488530"
}
]
},
{
"annotation": "Spitz Melanoma With SLC20A1::ALK Fusion: A Novel Fusion Previously Undescribed in Spitz Melanocytic Neoplasm.",
"evidence": [
{
"database": "RefSeq",
"id": "NP_004295",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
},
{
"database": "PubMed",
"id": "38941542",
"url": "https://glygen.org/publication/PubMed/38941542"
}
]
},
{
"annotation": "This gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).[provided by RefSeq, Jan 2011].",
"evidence": [
{
"database": "RefSeq",
"id": "NP_004295",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
}
]
},
{
"annotation": "[ALK rearranged Spitz melanocytoma: a clinicopathological and molecular genetic analysis of two cases].",
"evidence": [
{
"database": "RefSeq",
"id": "NP_004295",
"url": "https://www.ncbi.nlm.nih.gov/protein/NP_004295"
},
{
"database": "PubMed",
"id": "39103263",
"url": "https://glygen.org/publication/PubMed/39103263"
}
]
}
],
"disease": [
{
"disease_id": "DOID:0050741",
"recommended_name": {
"id": "DOID:0050741",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:0050741",
"name": "alcohol dependence",
"description": "A substance dependence that is characterized by tolerance, withdrawal symptoms, increasing use, persistent desire to decrease consumption, time spent obtaining or recovering from alcohol caused by a physical and psychological dependence on alcohol."
},
"synonyms": [
{
"id": "DOID:0050741",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:0050741",
"name": "alcoholism",
"description": ""
},
{
"id": "MONDO:0007079",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007079",
"name": "alcohol dependence",
"description": "Physical and psychological dependence on alcohol."
},
{
"id": "MONDO:0007079",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007079",
"name": "alcohol dependence",
"description": ""
},
{
"id": "MONDO:0007079",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007079",
"name": "alcoholism",
"description": ""
}
],
"unlinked_id_list": [],
"evidence": [
{
"id": "0050741",
"database": "AGR",
"url": "https://www.alliancegenome.org/disease/DOID:0050741"
}
]
},
{
"disease_id": "DOID:162",
"recommended_name": {
"id": "DOID:162",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:162",
"name": "cancer",
"description": "A disease of cellular proliferation that is malignant and primary, characterized by uncontrolled cellular proliferation, local cell invasion and metastasis."
},
"synonyms": [
{
"id": "DOID:162",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:162",
"name": "malignant neoplasm",
"description": ""
},
{
"id": "DOID:162",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:162",
"name": "malignant tumor",
"description": ""
},
{
"id": "DOID:162",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:162",
"name": "primary cancer",
"description": ""
}
],
"unlinked_id_list": [
"DOID:193",
"DOID:7757",
"DOID:2151",
"DOID:3316",
"DOID:370",
"DOID:706",
"DOID:5604",
"DOID:184",
"DOID:2599",
"DOID:4706",
"DOID:2174",
"DOID:4015",
"DOID:4203",
"DOID:170",
"DOID:10154",
"DOID:3017",
"DOID:5166",
"DOID:1795",
"DOID:3149",
"DOID:8527",
"DOID:0050938",
"DOID:3093",
"DOID:0060122",
"DOID:201",
"DOID:3303",
"DOID:3350",
"DOID:176",
"DOID:2595",
"DOID:5093",
"DOID:0070003",
"DOID:0080355",
"DOID:368",
"DOID:0080524",
"DOID:9460",
"DOID:0080639",
"DOID:0050619",
"DOID:0080638",
"DOID:4907",
"DOID:1325",
"DOID:688",
"DOID:771",
"DOID:0060073",
"DOID:672",
"DOID:5772",
"DOID:4645",
"DOID:0080879",
"DOID:4765",
"DOID:1357",
"DOID:5032",
"DOID:0060083",
"DOID:0050743",
"DOID:4045",
"DOID:5672",
"DOID:3675",
"DOID:5662",
"DOID:192",
"DOID:4043",
"DOID:0060116",
"DOID:0080364",
"DOID:0060100",
"DOID:3095",
"DOID:0080525",
"DOID:3541",
"DOID:4230",
"DOID:1294",
"DOID:0050615",
"DOID:0050687",
"DOID:3953",
"DOID:5158",
"DOID:1039",
"DOID:3973",
"DOID:8858",
"DOID:0060119",
"DOID:3111",
"DOID:60004",
"DOID:5467",
"DOID:1036",
"DOID:2706",
"DOID:3856",
"DOID:3112",
"DOID:3479",
"DOID:2815",
"DOID:660",
"DOID:120",
"DOID:2021",
"DOID:4114",
"DOID:0081452",
"DOID:4455",
"DOID:3451",
"DOID:175",
"DOID:4931",
"DOID:3277",
"DOID:1659",
"DOID:4960",
"DOID:3001",
"DOID:2621",
"DOID:1542",
"DOID:3419",
"DOID:6536",
"DOID:3850"
],
"evidence": [
{
"id": "162",
"database": "AGR",
"url": "https://www.alliancegenome.org/disease/DOID:162"
}
]
},
{
"disease_id": "DOID:769",
"recommended_name": {
"id": "DOID:769",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:769",
"name": "neuroblastoma",
"description": "An autonomic nervous system neoplasm that derives_from immature nerve cells."
},
"synonyms": [],
"unlinked_id_list": [],
"evidence": [
{
"id": "769",
"database": "AGR",
"url": "https://www.alliancegenome.org/disease/DOID:769"
}
]
},
{
"disease_id": "MONDO:0013083",
"recommended_name": {
"id": "MONDO:0013083",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013083",
"name": "neuroblastoma, susceptibility to, 3",
"description": "Any neuroblastoma in which the cause of the disease is a mutation in the ALK gene."
},
"synonyms": [
{
"id": "MONDO:0013083",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013083",
"name": "ALK neuroblastoma",
"description": ""
},
{
"id": "MONDO:0013083",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013083",
"name": "neuroblastoma caused by mutation in ALK",
"description": ""
},
{
"id": "MONDO:0013083",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013083",
"name": "neuroblastoma, susceptibility to, 3",
"description": ""
},
{
"id": "MONDO:0013083",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013083",
"name": "neuroblastoma, susceptibility to, type 3",
"description": ""
},
{
"id": "MONDO:0013083",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013083",
"name": "NBLST3",
"description": ""
},
{
"id": "MIM:613014",
"resource": "MIM",
"url": "https://www.omim.org/entry/613014",
"name": "Neuroblastoma 3",
"description": "Neuroblastoma 3"
}
],
"unlinked_id_list": [],
"evidence": [
{
"id": "613014",
"database": "MIM",
"url": "https://www.omim.org/entry/613014"
}
]
}
],
"snv": [],
"mutagenesis": [
{
"start_pos": 1507,
"end_pos": 1507,
"sequence_org": "Y",
"sequence_mut": "F",
"comment": "Impairs interaction with SHC1.",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
},
{
"database": "PubMed",
"id": "17274988",
"url": "https://glygen.org/publication/PubMed/17274988"
}
]
},
{
"start_pos": 48,
"end_pos": 52,
"sequence_org": "RLQRK",
"sequence_mut": "ELQEE",
"comment": "Abolished heparin-binding, leading to decreased ALK activation.",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
},
{
"database": "PubMed",
"id": "25605972",
"url": "https://glygen.org/publication/PubMed/25605972"
}
]
},
{
"start_pos": 859,
"end_pos": 859,
"sequence_org": "E",
"sequence_mut": "A",
"comment": "Slightly decreased autophosphorylation. Decreased autophosphorylation and subsequent activation; when associated with A-974.",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
},
{
"database": "PubMed",
"id": "34819673",
"url": "https://glygen.org/publication/PubMed/34819673"
}
]
},
{
"start_pos": 966,
"end_pos": 966,
"sequence_org": "Y",
"sequence_mut": "A",
"comment": "Slightly decreased autophosphorylation. Strongly reduced autophosphorylation and subsequent activation; when associated with A-994.",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
},
{
"database": "PubMed",
"id": "34819673",
"url": "https://glygen.org/publication/PubMed/34819673"
}
]
},
{
"start_pos": 974,
"end_pos": 974,
"sequence_org": "E",
"sequence_mut": "A",
"comment": "Slightly decreased autophosphorylation. Decreased autophosphorylation and subsequent activation; when associated with A-859.",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
},
{
"database": "PubMed",
"id": "34819673",
"url": "https://glygen.org/publication/PubMed/34819673"
}
]
},
{
"start_pos": 994,
"end_pos": 994,
"sequence_org": "E",
"sequence_mut": "A",
"comment": "SlStrongly reduced autophosphorylation and subsequent activation; when associated with A-966.",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
},
{
"database": "PubMed",
"id": "34819673",
"url": "https://glygen.org/publication/PubMed/34819673"
}
]
}
],
"expression_tissue": [
{
"tissue": {
"name": "Adult mammalian kidney",
"namespace": "UBERON",
"id": "0000082",
"url": "http://purl.obolibrary.org/obo/UBERON_0000082"
},
"score": "50.55",
"present": "MEDIUM",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000171094",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000171094"
}
]
},
{
"tissue": {
"name": "Oral cavity",
"namespace": "UBERON",
"id": "0000167",
"url": "http://purl.obolibrary.org/obo/UBERON_0000167"
},
"score": "58.55",
"present": "MEDIUM",
"evidence": [
{
"database": "Bgee",
"id": "ENSG00000171094",
"url": "https://bgee.org/?page=gene&gene_id=ENSG00000171094"
}
]
},
{
"tissue": {
"name": "Stomach",
"namespace": "UBERON",
"id": "0000945",
"url": "http://purl.obolibrary.org/obo/UBERON_0000945"
},
"score": "56.73",
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{
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},
{
"tissue": {
"name": "Uterus",
"namespace": "UBERON",
"id": "0000995",
"url": "http://purl.obolibrary.org/obo/UBERON_0000995"
},
"score": "82.4",
"present": "HIGH",
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{
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]
},
{
"tissue": {
"name": "Esophagus",
"namespace": "UBERON",
"id": "0001043",
"url": "http://purl.obolibrary.org/obo/UBERON_0001043"
},
"score": "63.82",
"present": "HIGH",
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{
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]
},
{
"tissue": {
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"namespace": "UBERON",
"id": "0001052",
"url": "http://purl.obolibrary.org/obo/UBERON_0001052"
},
"score": "54.8",
"present": "MEDIUM",
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{
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]
},
{
"tissue": {
"name": "Colon",
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"id": "0001155",
"url": "http://purl.obolibrary.org/obo/UBERON_0001155"
},
"score": "67.92",
"present": "HIGH",
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{
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]
},
{
"tissue": {
"name": "Urinary bladder",
"namespace": "UBERON",
"id": "0001255",
"url": "http://purl.obolibrary.org/obo/UBERON_0001255"
},
"score": "51.09",
"present": "MEDIUM",
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{
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}
]
},
{
"tissue": {
"name": "Thyroid gland",
"namespace": "UBERON",
"id": "0002046",
"url": "http://purl.obolibrary.org/obo/UBERON_0002046"
},
"score": "51.79",
"present": "MEDIUM",
"evidence": [
{
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"id": "ENSG00000171094",
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]
},
{
"tissue": {
"name": "Lung",
"namespace": "UBERON",
"id": "0002048",
"url": "http://purl.obolibrary.org/obo/UBERON_0002048"
},
"score": "66.64",
"present": "HIGH",
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{
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},
{
"tissue": {
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"namespace": "UBERON",
"id": "0002107",
"url": "http://purl.obolibrary.org/obo/UBERON_0002107"
},
"score": "38.66",
"present": "LOW",
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{
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}
]
},
{
"tissue": {
"name": "Prostate gland",
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"id": "0002367",
"url": "http://purl.obolibrary.org/obo/UBERON_0002367"
},
"score": "45.51",
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{
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}
]
},
{
"tissue": {
"name": "Thoracic mammary gland",
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"id": "0005200",
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},
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{
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}
]
}
],
"expression_disease": [
{
"significant": "No",
"trend": "down",
"name": "Prostate cancer [DO disease name]",
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"evidence": [
{
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],
"disease": [
{
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"url": "https://disease-ontology.org/term/DOID:10283",
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},
"synonyms": [
{
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"url": "https://disease-ontology.org/term/DOID:10283",
"name": "NGP - new growth of prostate",
"description": ""
},
{
"id": "DOID:10283",
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},
{
"id": "DOID:10283",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:10283",
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},
{
"id": "DOID:10283",
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"name": "prostate cancer, familial",
"description": ""
},
{
"id": "DOID:10283",
"resource": "Disease Ontology",
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},
{
"id": "DOID:10283",
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},
{
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},
{
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},
{
"id": "MONDO:0010257",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010257",
"name": "prostate cancer, hereditary, X-linked 1",
"description": ""
},
{
"id": "MONDO:0010257",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010257",
"name": "HPCX1",
"description": ""
},
{
"id": "MONDO:0010257",
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},
{
"id": "MONDO:0010405",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010405",
"name": "prostate cancer, hereditary, X-linked 2",
"description": ""
},
{
"id": "MONDO:0010405",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010405",
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},
{
"id": "MONDO:0010405",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0010405",
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},
{
"id": "MONDO:0011098",
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"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "prostate cancer, hereditary, 1",
"description": "Any familial prostate cancer in which the cause of the disease is a mutation in the RNASEL gene."
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "RNASEL familial prostate cancer",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "familial prostate cancer caused by mutation in RNASEL",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "prostate cancer 1",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "prostate cancer, hereditary, 1",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "prostate cancer, hereditary, type 1",
"description": ""
},
{
"id": "MONDO:0011098",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011098",
"name": "HPC1",
"description": ""
},
{
"id": "MONDO:0011270",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011270",
"name": "prostate cancer, hereditary, 8",
"description": ""
},
{
"id": "MONDO:0011270",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011270",
"name": "prostate cancer, hereditary, 8",
"description": ""
},
{
"id": "MONDO:0011270",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011270",
"name": "prostate cancer, hereditary, type 8",
"description": ""
},
{
"id": "MONDO:0011270",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0011270",
"name": "HPC8",
"description": ""
},
{
"id": "MONDO:0012093",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012093",
"name": "prostate cancer, hereditary, 3",
"description": ""
},
{
"id": "MONDO:0012093",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012093",
"name": "prostate cancer, hereditary, 3",
"description": ""
},
{
"id": "MONDO:0012093",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012093",
"name": "prostate cancer, hereditary, type 3",
"description": ""
},
{
"id": "MONDO:0012093",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012093",
"name": "prostate cancer, susceptibility to, 3",
"description": ""
},
{
"id": "MONDO:0012093",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012093",
"name": "HPC3",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "prostate cancer, hereditary, 4",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "prostate cancer, hereditary, 4",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "prostate cancer, hereditary, type 4",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "prostate cancer, susceptibility to, 4",
"description": ""
},
{
"id": "MONDO:0012094",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012094",
"name": "HPC4",
"description": ""
},
{
"id": "MONDO:0012244",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012244",
"name": "prostate cancer, hereditary, 5",
"description": ""
},
{
"id": "MONDO:0012244",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012244",
"name": "prostate cancer, hereditary, 5",
"description": ""
},
{
"id": "MONDO:0012244",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012244",
"name": "prostate cancer, hereditary, type 5",
"description": ""
},
{
"id": "MONDO:0012244",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012244",
"name": "HPC5",
"description": ""
},
{
"id": "MONDO:0012300",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012300",
"name": "prostate cancer, hereditary, 6",
"description": ""
},
{
"id": "MONDO:0012300",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012300",
"name": "prostate cancer, hereditary, 6",
"description": ""
},
{
"id": "MONDO:0012300",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012300",
"name": "prostate cancer, hereditary, type 6",
"description": ""
},
{
"id": "MONDO:0012300",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012300",
"name": "HPC6",
"description": ""
},
{
"id": "MONDO:0012470",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012470",
"name": "prostate cancer, hereditary, 7",
"description": ""
},
{
"id": "MONDO:0012470",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012470",
"name": "HPC7",
"description": ""
},
{
"id": "MONDO:0012470",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012470",
"name": "prostate cancer, hereditary, 7",
"description": ""
},
{
"id": "MONDO:0012597",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012597",
"name": "prostate cancer, hereditary, 9",
"description": ""
},
{
"id": "MONDO:0012597",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012597",
"name": "prostate cancer, hereditary, 9",
"description": ""
},
{
"id": "MONDO:0012597",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012597",
"name": "prostate cancer, hereditary, type 9",
"description": ""
},
{
"id": "MONDO:0012597",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012597",
"name": "HPC9",
"description": ""
},
{
"id": "MONDO:0012620",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012620",
"name": "prostate cancer, hereditary, 10",
"description": ""
},
{
"id": "MONDO:0012620",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012620",
"name": "HPC10",
"description": ""
},
{
"id": "MONDO:0012620",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012620",
"name": "prostate cancer, hereditary, 10",
"description": ""
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "prostate cancer, hereditary, 12",
"description": "Any familial prostate cancer in which the cause of the disease is a mutation in the EHBP1 gene."
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "EHBP1 familial prostate cancer",
"description": ""
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "familial prostate cancer caused by mutation in EHBP1",
"description": ""
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "prostate cancer, hereditary, 12",
"description": ""
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "prostate cancer, hereditary, type 12",
"description": ""
},
{
"id": "MONDO:0012741",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012741",
"name": "HPC12",
"description": ""
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "prostate cancer, hereditary, 13",
"description": "Any familial prostate cancer in which the cause of the disease is a mutation in the MSMB gene."
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "MSMB familial prostate cancer",
"description": ""
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "familial prostate cancer caused by mutation in MSMB",
"description": ""
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "prostate cancer, hereditary, 13",
"description": ""
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "prostate cancer, hereditary, type 13",
"description": ""
},
{
"id": "MONDO:0012758",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012758",
"name": "HPC13",
"description": ""
},
{
"id": "MONDO:0012768",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012768",
"name": "prostate cancer, hereditary, 11",
"description": ""
},
{
"id": "MONDO:0012768",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012768",
"name": "HPC11",
"description": ""
},
{
"id": "MONDO:0012768",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012768",
"name": "prostate cancer, hereditary, 11",
"description": ""
},
{
"id": "MONDO:0012769",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012769",
"name": "prostate cancer, hereditary, 14",
"description": ""
},
{
"id": "MONDO:0012769",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012769",
"name": "HPC14",
"description": ""
},
{
"id": "MONDO:0012769",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012769",
"name": "prostate cancer, hereditary, 14",
"description": ""
},
{
"id": "MONDO:0012770",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012770",
"name": "prostate cancer, hereditary, 15",
"description": ""
},
{
"id": "MONDO:0012770",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012770",
"name": "HPC15",
"description": ""
},
{
"id": "MONDO:0012770",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0012770",
"name": "prostate cancer, hereditary, 15",
"description": ""
},
{
"id": "MONDO:0700275",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0700275",
"name": "prostate cancer, hereditary",
"description": "An instance of prostate cancer that is caused by an inherited genomic modification in an individual. Familial prostate cancer (FPC) is a malignant tumor of the prostate with an early onset. FPC is either asymptomatic or causes mictionary symptoms, erectile dysfunction, bone pain, venous compression and infectious or inflammatory syndrome (for the metastatic forms). It is also characterized by familial antecedents."
},
{
"id": "MIM:601518",
"resource": "MIM",
"url": "https://www.omim.org/entry/601518",
"name": "Prostate cancer, hereditary, 1",
"description": "Prostate cancer, hereditary, 1"
},
{
"id": "MIM:610997",
"resource": "MIM",
"url": "https://www.omim.org/entry/610997",
"name": "Prostate cancer, hereditary, 9",
"description": "Prostate cancer, hereditary, 9"
},
{
"id": "MIM:611868",
"resource": "MIM",
"url": "https://www.omim.org/entry/611868",
"name": "Prostate cancer, hereditary, 12",
"description": "Prostate cancer, hereditary, 12"
},
{
"id": "MIM:611928",
"resource": "MIM",
"url": "https://www.omim.org/entry/611928",
"name": "Prostate cancer, hereditary, 13",
"description": "Prostate cancer, hereditary, 13"
},
{
"id": "MIM:611955",
"resource": "MIM",
"url": "https://www.omim.org/entry/611955",
"name": "Prostate cancer, hereditary, 11",
"description": "Prostate cancer, hereditary, 11"
},
{
"id": "MIM:176807",
"resource": "MIM",
"url": "https://www.omim.org/entry/176807",
"name": "Prostate cancer",
"description": "Prostate cancer"
}
],
"unlinked_id_list": [],
"evidence": [
{
"id": "10283",
"database": "AGR",
"url": "https://www.alliancegenome.org/disease/DOID:10283"
}
]
}
]
},
{
"significant": "Yes",
"trend": "down",
"name": "Stomach cancer [DO disease name]",
"url": "https://disease-ontology.org/term/DOID:10534",
"evidence": [
{
"database": "BioXpress",
"id": "Q9UM73",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/Q9UM73"
}
],
"disease": [
{
"disease_id": "DOID:10534",
"recommended_name": {
"id": "DOID:10534",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:10534",
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{
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{
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},
{
"id": "MONDO:0001056",
"resource": "MONDO",
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"name": "Ca lesser curvature - stomach",
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},
{
"id": "MONDO:0001056",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0001056",
"name": "GC",
"description": ""
},
{
"id": "MONDO:0001056",
"resource": "MONDO",
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{
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},
{
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"name": "gastric cancer risk after h. pylori infection",
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},
{
"id": "MONDO:0001056",
"resource": "MONDO",
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"name": "gastric cancer, somatic",
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},
{
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"resource": "MONDO",
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},
{
"id": "MONDO:0001056",
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},
{
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{
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{
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},
{
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{
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},
{
"id": "MONDO:0001056",
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"name": "malignant tumor of body of stomach",
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},
{
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},
{
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},
{
"id": "MONDO:0001056",
"resource": "MONDO",
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},
{
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},
{
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},
{
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},
{
"id": "MONDO:0001056",
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},
{
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},
{
"id": "MONDO:0001056",
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{
"id": "MONDO:0001056",
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},
{
"id": "MONDO:0001056",
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},
{
"id": "MONDO:0001056",
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},
{
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{
"id": "MIM:613659",
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{
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{
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{
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{
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{
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{
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"id": "MONDO:0012955",
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"url": "https://monarchinitiative.org/disease/MONDO:0012955",
"name": "lung cancer susceptibility 4",
"description": ""
},
{
"id": "MONDO:0013631",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013631",
"name": "lung cancer susceptibility 5",
"description": ""
},
{
"id": "MONDO:0013631",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013631",
"name": "LNCR5",
"description": ""
},
{
"id": "MONDO:0013631",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0013631",
"name": "lung cancer susceptibility 5",
"description": ""
},
{
"id": "MIM:211980",
"resource": "MIM",
"url": "https://www.omim.org/entry/211980",
"name": "Lung cancer",
"description": "Lung cancer"
}
],
"unlinked_id_list": [
"DOID:4765"
],
"evidence": [
{
"id": "1324",
"database": "AGR",
"url": "https://www.alliancegenome.org/disease/DOID:1324"
}
]
}
]
},
{
"significant": "Yes",
"trend": "down",
"name": "Breast cancer [DO disease name]",
"url": "https://disease-ontology.org/term/DOID:1612",
"evidence": [
{
"database": "BioXpress",
"id": "Q9UM73",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/Q9UM73"
}
],
"disease": [
{
"disease_id": "DOID:1612",
"recommended_name": {
"id": "DOID:1612",
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"url": "https://disease-ontology.org/term/DOID:1612",
"name": "breast cancer",
"description": "An organ system cancer that originates in the mammary gland."
},
"synonyms": [
{
"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1612",
"name": "breast tumor",
"description": ""
},
{
"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1612",
"name": "malignant neoplasm of breast",
"description": ""
},
{
"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1612",
"name": "malignant tumor of the breast",
"description": ""
},
{
"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1612",
"name": "mammary cancer",
"description": ""
},
{
"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1612",
"name": "mammary tumor",
"description": ""
},
{
"id": "DOID:1612",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1612",
"name": "primary breast cancer",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "hereditary breast carcinoma",
"description": "Breast carcinoma that has developed in relatives of patients with history of breast carcinoma."
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer susceptibility, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, early-onset, susceptibility to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, invasive ductal, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, lobular, somatic",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, male, susceptibility to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, protection against, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, somatic",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "breast cancer, susceptibility to, autosomal dominant, somatic mutation",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "familial breast cancer",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "familial breast carcinoma",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "familial cancer of breast",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "familial cancer of the breast",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "hereditary breast cancer",
"description": ""
},
{
"id": "MONDO:0016419",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0016419",
"name": "hereditary breast carcinoma",
"description": ""
},
{
"id": "MIM:114480",
"resource": "MIM",
"url": "https://www.omim.org/entry/114480",
"name": "Breast cancer",
"description": "Breast cancer"
}
],
"unlinked_id_list": [
"DOID:3017",
"DOID:0050938"
],
"evidence": [
{
"id": "1612",
"database": "AGR",
"url": "https://www.alliancegenome.org/disease/DOID:1612"
}
]
}
]
},
{
"significant": "Yes",
"trend": "up",
"name": "Thyroid cancer [DO disease name]",
"url": "https://disease-ontology.org/term/DOID:1781",
"evidence": [
{
"database": "BioXpress",
"id": "Q9UM73",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/Q9UM73"
}
],
"disease": [
{
"disease_id": "DOID:1781",
"recommended_name": {
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1781",
"name": "thyroid cancer",
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},
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{
"id": "DOID:1781",
"resource": "Disease Ontology",
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"description": ""
},
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1781",
"name": "malignant neoplasm of thyroid gland",
"description": ""
},
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1781",
"name": "malignant tumour of thyroid gland",
"description": ""
},
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1781",
"name": "neoplasm of thyroid gland",
"description": ""
},
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1781",
"name": "thyroid neoplasm",
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},
{
"id": "DOID:1781",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:1781",
"name": "thyroid gland cancer",
"description": ""
}
],
"unlinked_id_list": [
"DOID:3973",
"DOID:0080524",
"DOID:0080525"
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"evidence": [
{
"id": "1781",
"database": "AGR",
"url": "https://www.alliancegenome.org/disease/DOID:1781"
}
]
}
]
},
{
"significant": "Yes",
"trend": "up",
"name": "Kidney cancer [DO disease name]",
"url": "https://disease-ontology.org/term/DOID:263",
"evidence": [
{
"database": "BioXpress",
"id": "Q9UM73",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/Q9UM73"
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],
"disease": [
{
"disease_id": "DOID:263",
"recommended_name": {
"id": "DOID:263",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:263",
"name": "kidney cancer",
"description": "A urinary system cancer that is located_in the kidney."
},
"synonyms": [
{
"id": "DOID:263",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:263",
"name": "malignant neoplasm of kidney except pelvis",
"description": ""
},
{
"id": "DOID:263",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:263",
"name": "malignant tumour of kidney",
"description": ""
},
{
"id": "DOID:263",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:263",
"name": "renal cancer",
"description": ""
}
],
"unlinked_id_list": [
"DOID:3675",
"DOID:4455"
],
"evidence": [
{
"id": "263",
"database": "AGR",
"url": "https://www.alliancegenome.org/disease/DOID:263"
}
]
}
]
},
{
"significant": "No",
"trend": "down",
"name": "Liver cancer [DO disease name]",
"url": "https://disease-ontology.org/term/DOID:3571",
"evidence": [
{
"database": "BioXpress",
"id": "Q9UM73",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/Q9UM73"
}
],
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{
"disease_id": "DOID:3571",
"recommended_name": {
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "liver cancer",
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},
"synonyms": [
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "Ca liver - primary",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "Resectable malignant neoplasm of Liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "hepatic cancer",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "hepatic neoplasm",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "malignant hepato-biliary neoplasm",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "malignant neoplasm of liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "malignant neoplasm of liver, primary",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "malignant tumor of liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "neoplasm of liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "non-resectable primary hepatic malignant neoplasm",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "primary liver cancer",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
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"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "resectable malignant neoplasm of the liver",
"description": ""
},
{
"id": "DOID:3571",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:3571",
"name": "malignant neoplasm of liver, not specified as primary or secondary",
"description": ""
}
],
"unlinked_id_list": [],
"evidence": [
{
"id": "3571",
"database": "AGR",
"url": "https://www.alliancegenome.org/disease/DOID:3571"
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]
}
]
},
{
"significant": "Yes",
"trend": "up",
"name": "Uterine cancer [DO disease name]",
"url": "https://disease-ontology.org/term/DOID:363",
"evidence": [
{
"database": "BioXpress",
"id": "Q9UM73",
"url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/Q9UM73"
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],
"disease": [
{
"disease_id": "DOID:363",
"recommended_name": {
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"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:363",
"name": "uterine cancer",
"description": "A female reproductive organ cancer that is located_in the uterus."
},
"synonyms": [
{
"id": "DOID:363",
"resource": "Disease Ontology",
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},
{
"id": "DOID:363",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:363",
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"description": ""
},
{
"id": "DOID:363",
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"url": "https://disease-ontology.org/term/DOID:363",
"name": "malignant neoplasm of uterus",
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},
{
"id": "DOID:363",
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},
{
"id": "DOID:363",
"resource": "Disease Ontology",
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"name": "neoplasm of uterus",
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},
{
"id": "DOID:363",
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"name": "uterine tumor",
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},
{
"id": "DOID:363",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:363",
"name": "uterus neoplasm",
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}
],
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"id": "363",
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},
{
"significant": "Yes",
"trend": "down",
"name": "Esophageal cancer [DO disease name]",
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{
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{
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"name": "Ca lower third oesophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "Ca middle third oesophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "esophagus cancer",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "malignant neoplasm of distal third of esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "malignant neoplasm of lower third of oesophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "malignant neoplasm of middle third of oesophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "malignant neoplasm of proximal third of esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "malignant neoplasm of upper third esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "malignant tumor of Distal Third of esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "malignant tumor of Proximal Third of esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "malignant tumor of abdominal esophagus",
"description": ""
},
{
"id": "DOID:5041",
"resource": "Disease Ontology",
"url": "https://disease-ontology.org/term/DOID:5041",
"name": "malignant tumor of the middle Third of the esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophageal cancer",
"description": "A primary or metastatic malignant neoplasm involving the esophagus."
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "cancer of esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "cancer of oesophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophageal cancer",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophageal cancer, somatic",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophageal carcinoma, somatic",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophageal squamous cell carcinoma, somatic",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "esophagus cancer",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant esophageal neoplasm",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant esophageal tumor",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant esophageal tumour",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant esophagus neoplasm",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant esophagus tumor",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of esophagus",
"description": ""
},
{
"id": "MONDO:0007576",
"resource": "MONDO",
"url": "https://monarchinitiative.org/disease/MONDO:0007576",
"name": "malignant neoplasm of oesophagus",
"description": ""
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{
"id": "6EBW",
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{
"id": "6EDL",
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{
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{
"id": "7BTT",
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{
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{
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{
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{
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{
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{
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{
"id": "7MZW",
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{
"id": "7MZY",
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{
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{
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{
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{
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},
{
"id": "7R7R",
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{
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{
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{
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{
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{
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{
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{
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},
{
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{
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{
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{
"id": "R-HSA-9717264",
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{
"id": "R-HSA-9717301",
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{
"id": "R-HSA-9717316",
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]
},
{
"id": "R-HSA-9717319",
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},
{
"id": "R-HSA-9717323",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9717323",
"database": "Reactome",
"categories": [
"Enzyme and Pathway"
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},
{
"id": "R-HSA-9717326",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9717326",
"database": "Reactome",
"categories": [
"Enzyme and Pathway"
]
},
{
"id": "R-HSA-9717329",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9717329",
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]
},
{
"id": "R-HSA-9725370",
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},
{
"id": "R-HSA-9851151",
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},
{
"id": "NP_004295",
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},
{
"id": "10596",
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},
{
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]
},
{
"id": "A0A087WZL3-1",
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]
},
{
"id": "E7EPW7",
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]
},
{
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]
},
{
"id": "H7BZ33",
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]
},
{
"id": "H7BZ33-1",
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"categories": [
"Protein"
]
},
{
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73",
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"categories": [
"Protein"
]
},
{
"id": "Q9UM73-1",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73-1",
"database": "UniProtKB",
"categories": [
"Protein"
]
}
],
"sequence": {
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"length": 1620,
"header": "sp|Q9UM73-1|ALK_HUMAN Isoform 1 of ALK tyrosine kinase receptor OS=Homo sapiens OX=9606 GN=ALK PE=1 SV=3 CANONICAL=Q9UM73-1"
},
"isoforms": [
{
"isoform_ac": "A0A087WZL3-1",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73/entry#A0A087WZL3-1",
"sequence": {
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"length": 1243,
"header": "tr|A0A087WZL3-1|A0A087WZL3_HUMAN Computationally mapped isoform of Tyrosine-protein kinase receptor OS=Homo sapiens OX=9606 GN=ALK PE=1 SV=1 CANONICAL=Q9UM73-1"
},
"locus": {
"chromosome": "2",
"start_pos": 29531937,
"end_pos": 29193227,
"strand": "+",
"evidence": [
{
"database": "Ensembl Transcript",
"id": "ENST00000618119.4",
"url": "https://www.ensembl.org/id/ENST00000618119.4"
},
{
"database": "Ensembl Peptide",
"id": "ENSP00000482733.1",
"url": "https://www.ensembl.org/id/ENSP00000482733.1"
}
]
}
},
{
"isoform_ac": "E7EPW7-1",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73/entry#E7EPW7-1",
"sequence": {
"sequence": "XNDPEMDGEDGVSFISPLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLAEDGVSCIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIGNPNLITVGPLHRGGN",
"length": 129,
"header": "tr|E7EPW7-1|E7EPW7_HUMAN Computationally mapped isoform of ALK receptor tyrosine kinase OS=Homo sapiens OX=9606 GN=ALK PE=1 SV=3 CANONICAL=Q9UM73-1"
},
"locus": {
"chromosome": "2",
"start_pos": 29227653,
"end_pos": 29224630,
"strand": "+",
"evidence": [
{
"database": "Ensembl Transcript",
"id": "ENST00000431873.6",
"url": "https://www.ensembl.org/id/ENST00000431873.6"
},
{
"database": "Ensembl Peptide",
"id": "ENSP00000414027.3",
"url": "https://www.ensembl.org/id/ENSP00000414027.3"
}
]
}
},
{
"isoform_ac": "H7BZ33-1",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73/entry#H7BZ33-1",
"sequence": {
"sequence": "SSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISLSWKQLFCFTFCLRPSWEKSTMNSSTQSTHQYLRKTLSCPLRHFLTQVPEQHPHSSSHSPANGTPVEPAVVLPTCSPARFWV",
"length": 152,
"header": "tr|H7BZ33-1|ALK_HUMAN Computationally mapped isoform of ALK tyrosine kinase receptor OS=Homo sapiens OX=9606 GN=ALK PE=1 SV=1 CANONICAL=Q9UM73-1"
},
"locus": {
"chromosome": "2",
"start_pos": 29223394,
"end_pos": 29220991,
"strand": "+",
"evidence": [
{
"database": "Ensembl Transcript",
"id": "ENST00000453137.1",
"url": "https://www.ensembl.org/id/ENST00000453137.1"
},
{
"database": "Ensembl Peptide",
"id": "ENSP00000387488.1",
"url": "https://www.ensembl.org/id/ENSP00000387488.1"
}
]
}
},
{
"isoform_ac": "Q9UM73-1",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73/entry#Q9UM73-1",
"sequence": {
"sequence": "MGAIGLLWLLPLLLSTAAVGSGMGTGQRAGSPAAGPPLQPREPLSYSRLQRKSLAVDFVVPSLFRVYARDLLLPPSSSELKAGRPEARGSLALDCAPLLRLLGPAPGVSWTAGSPAPAEARTLSRVLKGGSVRKLRRAKQLVLELGEEAILEGCVGPPGEAAVGLLQFNLSELFSWWIRQGEGRLRIRLMPEKKASEVGREGRLSAAIRASQPRLLFQIFGTGHSSLESPTNMPSPSPDYFTWNLTWIMKDSFPFLSHRSRYGLECSFDFPCELEYSPPLHDLRNQSWSWRRIPSEEASQMDLLDGPGAERSKEMPRGSFLLLNTSADSKHTILSPWMRSSSEHCTLAVSVHRHLQPSGRYIAQLLPHNEAAREILLMPTPGKHGWTVLQGRIGRPDNPFRVALEYISSGNRSLSAVDFFALKNCSEGTSPGSKMALQSSFTCWNGTVLQLGQACDFHQDCAQGEDESQMCRKLPVGFYCNFEDGFCGWTQGTLSPHTPQWQVRTLKDARFQDHQDHALLLSTTDVPASESATVTSATFPAPIKSSPCELRMSWLIRGVLRGNVSLVLVENKTGKEQGRMVWHVAAYEGLSLWQWMVLPLLDVSDRFWLQMVAWWGQGSRAIVAFDNISISLDCYLTISGEDKILQNTAPKSRNLFERNPNKELKPGENSPRQTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVEVGSEGPLKGIQIWKVPATDTYSISGYGAAGGKGGKNTMMRSHGVSVLGIFNLEKDDMLYILVGQQGEDACPSTNQLIQKVCIGENNVIEEEIRVNRSVHEWAGGGGGGGGATYVFKMKDGVPVPLIIAAGGGGRAYGAKTDTFHPERLENNSSVLGLNGNSGAAGGGGGWNDNTSLLWAGKSLQEGATGGHSCPQAMKKWGWETRGGFGGGGGGCSSGGGGGGYIGGNAASNNDPEMDGEDGVSFISPLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLAEDGVSCIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSSGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEPSSLTANMKEVPLFRLRHFPCGNVNYGYQQQGLPLEAATAPGAGHYEDTILKSKNSMNQPGP",
"length": 1620,
"header": "sp|Q9UM73-1|ALK_HUMAN Isoform 1 of ALK tyrosine kinase receptor OS=Homo sapiens OX=9606 GN=ALK PE=1 SV=3 CANONICAL=Q9UM73-1"
},
"locus": {
"chromosome": "2",
"start_pos": 29920659,
"end_pos": 29193227,
"strand": "+",
"evidence": [
{
"database": "Ensembl Transcript",
"id": "ENST00000389048.8",
"url": "https://www.ensembl.org/id/ENST00000389048.8"
},
{
"database": "Ensembl Peptide",
"id": "ENSP00000373700.3",
"url": "https://www.ensembl.org/id/ENSP00000373700.3"
}
]
}
}
],
"glycosylation": [
{
"glytoucan_ac": "",
"type": "O-linked",
"subtype": "other",
"prediction_tool_list": [
{
"label": "isoglyp",
"url": "https://github.com/jonmohl/ISOGlyP"
}
],
"site_category": "predicted",
"site_category_dict": {
"predicted": true
},
"site_seq": "",
"relation": "attached",
"comment": "",
"icn3d_view": {},
"start_pos": 1026,
"start_aa": "Thr",
"end_pos": 1026,
"end_aa": "Thr",
"residue": "Thr",
"site_lbl": "Thr1026",
"evidence": [
{
"id": "GLY_001151",
"database": "GlyGen",
"url": "https://data.glygen.org/GLY_001151"
}
],
"filter_code": "00000000000000001000.00000000001000.0.01001"
},
{
"glytoucan_ac": "",
"type": "O-linked",
"subtype": "other",
"prediction_tool_list": [],
"site_category": "automatic_literature_mining",
"site_category_dict": {
"automatic_literature_mining": true
},
"site_seq": "Y",
"relation": "attached",
"comment": "",
"icn3d_view": {},
"start_pos": 1604,
"start_aa": "Tyr",
"end_pos": 1604,
"end_aa": "Tyr",
"residue": "Tyr",
"site_lbl": "Tyr1604",
"evidence": [
{
"id": "34270745",
"database": "PubMed",
"url": "https://glygen.org/publication/PubMed/34270745"
},
{
"id": "GLY_000481",
"database": "GlyGen",
"url": "https://data.glygen.org/GLY_000481"
}
],
"mining_tool": "GlycoSiteMiner_1.0",
"mining_tool_list": [
{
"label": "GlycoSiteMiner_1.0"
}
],
"filter_code": "00000000000000000010.00000000001000.00.01011"
},
{
"glytoucan_ac": "",
"type": "N-linked",
"subtype": "other",
"prediction_tool_list": [],
"site_category": "predicted",
"site_category_dict": {
"predicted": true
},
"site_seq": "N",
"relation": "attached",
"comment": "N-linked (GlcNAc...) asparagine",
"icn3d_view": {},
"start_pos": 169,
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"sequence": "MPRLFLFPGSDVSVSRPAGNRRGSGDSSETAGHAYKLQPGSRVASSQPPSLAGTKRSKDRAMGYSRQLLLCLGAAGIILCSNSEFQAPFLTPSPLPVLVLNSQEERIIPTPSRLKPASLPNPLGKRGPWVINTCGASGRRGPTQTQCDRAYTGNSVMVTVGAAGPLKGVQLWRAPDTGQYISAYGAAGGKGARNHLSRAHGIFLSAVFFLSRGEPVYILVGQQGQDACPGGSPESQLVCLGESGEHETTDGSERVPGWRRWAGGGGGGGGATYIFRLRTGKPEPLLVAAGGGGRSYRRRPERGWTQAAPERLETRAAAQGSGRRGGAAGVRGGWTSRAPSPQAGRSPGEGAEGGEGCAEAWAALRWAAEGGFGGGGGACAAGGGSGGYRGGDTSESDLLWADGEDGISFVHPSGELYLQPLAVTEGDVEVEIRRHPNCSHCSFKDCQWQAELWRAECICPEGMELAVDNITCTGLPTTTSPLIMMGAVVTALTLSLLMMCGVLILVNQKKCQSLRGTRLPGPELELSKLRTSAIRTAPNPYYCQVGLSPAQAWPLPQGLTEVSPANVTLLRALGHGAFGEVYEGLVIGLPGDSSPLPVAIKTLPELCSPQDELDFLMEALIISKFSHQNIVRCVGLSFQAAPRLILLELMSGGDMKSFLRHSRPHPGQLSPLTMQDLLQLAQDIAQGCHYLEENHFIHRDIAARNCLLSCSGDSRVAKIGDFGMARDIYQASYYRKGGRTLLPVKWMPPEALLEGLFTSKTDSWSFGVLLWEIFSLGYMPYPGHTNQEVLDFIATGNRMDPPRNCPGPVYRIMTQCWQLQPELRPDFASILERIQYCIQDPDVLNSPLPMEPGPIVEEEGASGPGNRSLEGLRSPKTLELSSQNLKSRGGDLLGSQLPSGLKTLTSRCLQPQNIWNPTYGSWTPRSPQGEDSDIDLSNGPSSDSFPGEQ",
"length": 949
},
"evidence": [
{
"id": "ZFIN:ZDB-GENE-030616-115",
"url": "https://alliancegenome.org/gene/ZFIN:ZDB-GENE-030616-115#orthology",
"database": "AGR"
}
],
"glygen_name": "Rat",
"common_name": "Rat"
},
{
"uniprot_canonical_ac": "F1LRZ0-1",
"protein_name": "Tyrosine-protein kinase receptor",
"gene_name": "Alk",
"tax_id": 10116,
"organism": "Rattus norvegicus",
"sequence": {
"sequence": "MGALGFLWLLPPLLLTAASYSGAATDQRAGSPASGPPLQPREPLSYSRLQRKSLAVDFVVPSLFRVYARDLLLPQPPSPSEPGAGGLEARGSLALDCDPLLRLLGPSPGISWAEGASSPSPEAAPTLSRVLKGGSVRKLRRAKQLVLELGEETILEGCIGPPEEAAAVGILQFNLSELFSWWILHGEGRLRIRLMPEKKASEVGREGRLSTAIRASQPRLLFQIFGTGHSSLESPSEMPSPPGNFLWNLTWTMKDSFPFLSHRSRYGLECSFDFPCELEYSPPLHTHGNQSWSWRRVPSEEASRMNLLDGPEAEHLKEMPRGSFLLLNTSADSKHTILSPWMRSSSEHCTLAVSVHRHLQPSGRYVAQLLPHNEAGREILLVPTPGKHGWTVLHGRVGRPENPFRVALEYISSGNRSLSAVDFFALKNCSEGTSPGSKMALQSSFTCWNGTVLQLGQACDFHQNCAQGEDEGQLCSKLPAGFYCNFEDGFCGWTQSPLSPRVPRWQVKTLKDTHSQGHQGHALLLSTTDDPTSESATVTSATFPAPMKSSPCELRMSWLIRGVLKGNVSLVLVENKTGKEQSRTVWHVATNEGLSLWQWTVLSLLDVTDRFWLQIVTWWGPGSRATVAFDNISISLDCYLTISGEEKMSLNAVPKSRNLFEKNPNKEPKPWANISGPTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVVVGSEGPLRGIQIWKVPATDTYSISGYGAAGGKGGKNTMMRSHGVSVLGIFNLEKDDTLYILVGQQGEDACPRANQLIQKVCVGENNVIEEEIRVNRSVHEWAGGGGGGGGATYVFKMKDGVPVPLIIAAGGGGRAYGAKTETFHPERLENNSSVLGLNGNSGAAGGGGGWNDNTSLLWAGKSLLEGAAGGHSCPQAMKKWGWETRGGFGGGGGGCSSGGGGGGYIGGNAASNNDPEMDGEDGVSFISPLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLADDGVSCIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQALPRFILLELMAGGDLKSFLRETRPRPNQPTSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGAGRIAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPVVEEEEKVPMRPKDPEGMPPLLVSPQSAKHEEASSAPQPSALAAPGPLVKKPSGAGAGAGAGPVPRGAADRGHVNMAFSQPNPPPELHKGPGSRNKPTSLWNPTYGSWFTEKPAKKTHPPPGAEPQARAGAAEGGWTGPGAGPRRAEAALLLEPSALSATMKEVPLFRLRHFPCGNVNYGYQQQGLPLEATAAPGDTVLKSKTKVTQPGP",
"length": 1617
},
"evidence": [
{
"id": "HGNC:427",
"url": "https://alliancegenome.org/gene/HGNC:427#orthology",
"database": "AGR"
},
{
"id": "RGD:628622",
"url": "https://alliancegenome.org/gene/RGD:628622#orthology",
"database": "AGR"
},
{
"id": "MGI:103305",
"url": "https://alliancegenome.org/gene/MGI:103305#orthology",
"database": "AGR"
},
{
"id": "ZFIN:ZDB-GENE-031027-1",
"url": "https://alliancegenome.org/gene/ZFIN:ZDB-GENE-031027-1#orthology",
"database": "AGR"
},
{
"id": "Q9UM73",
"url": "https://omabrowser.org/oma/group/Q9UM73/",
"database": "OMA"
}
],
"glygen_name": "Rat",
"common_name": "Rat"
},
{
"uniprot_canonical_ac": "F1QVU0-1",
"protein_name": "Tyrosine-protein kinase receptor",
"gene_name": "ltk",
"tax_id": 7955,
"organism": "Danio rerio",
"sequence": {
"sequence": "MDYITRQTFVKLALFIFTVLRSSCALLEKAAEDPVHPNPLQSSPAEDSDVSFCDFESPCSWTLSSHSTGGDWFITSAQQHRSSRRDTQPIRDYSTGKSEGHFLLLKPSSSHLSAGRCSFHMTSPVVLSSGPFCHLQLARFQPEPHAGNISAFVKHTDSTDIKPIDLTIKEQESDSSQWEVLEAVIGQLNEPFQVTVQYSACSSHEVGFLAFDSLELKNCVMGDDYVDLGSDCEKYSSLQCHSGGCIEKQRVCDFHTDCPEGEDEGLICSTLPLGSYCSFELGSCGWLAADTQSSWRLVSGQQLIEDTHLLGTTLKNTQGHFLFLKVRGHGDEREALVQSPALPSTISNQDCQLQFSLYRYGDFNGTVLLSVVESGASAPALIWERSGHWKDAWQEITLPITEILNGFHLKVQAFWTSGSKADIALDDISLSAACFDTELNELLHEGLPHDLDFSPLPEPSASEASPITWWFTSCGASGPFGPTQAQCDSAYRNTNVSVVVGKEGPLRGVQMWKVPATNTYKISAYGAAGGKGAKNHNKRSHGVFISATFPLEKGDILYILIGHQGEDACPGRNPQTHKICLGESSVIEDGFDSDGSALKWAGGGGGGGGATYIYRMENGQPLPLLIAAGGGGKAYLEDPESSQDQSFREQYENDTTVSGVSGRSGAAGGGGGWSDVSSLSWAGKSLVEGGQGGSSCPEALSVLGWATFGGFGGGGGACSAGGGGGGYRGGDAPLLDDISADGQDGLSFVHPMGKIFLQPLAAMESHGEAEIVVYLNCSHCKTQSCKRDEDTKLILCLCDSDEVLAPDNVTCAGTKHSLCQFINKHLQHNSSPLVCPPLVVPMGSLADGPPSLVFIMAVIVSTVVTGVVLTCASLTLIYYRKKNHLHAVRIRLQSPEYKLSKIRSSTIMTDYNPNYGYFGKAASLSELKEVPRKNITLLRALGHGAFGEVYEGQVLGMNGENTAMQVAIKTLPEICSEQDEMDFLMEALIMSKFSHQNIVRCIGVSLQILPRFILLELMTGGDMKSFLRLNRPRTNHSSSLSMLELLHMARDIALGCRYLEENHFIHRDIAARNCLLTCPGPDRVAKIGDFGMARDIYRASYYRKGGRAMLPVKWMPPEAFLEGIFTCKTDTWSFGVLLWEIFSLGYMPYPCKTNQEVLEFVTGGGRMDPPKSCPGPVYRIMTQCWQHCPEHRPNFTTILERINYCTQDPDVINTPLPVECGPPVEEEGGTVIRPDGSGSMTPLLVARSLSQDASPRASITSVTPQALKPRLQLQRPVHLTQEVGTYRETLEPCWAEPVPASGVCPGPWLQVPEHRPCSRSSSSSGSQKLKNKTKNLWNPTYGSWVLESFGRGKSALCHTQSMPLSCNPTSVSAPSSTSEHTDPVVEVNANVSASPPPSAAPSQTTLTPTAAPSRKSPTGAAGVSLATVMDLAKLQSFPCGNVNYAYDEQSYETESLPVVVSKSLEPSTSSAATSSLVALSQPGSFTHKPLVKRHASYGHEDVRRYTQPEKPTRDRDSGFSLSEDLSVTPV",
"length": 1530
},
"evidence": [
{
"id": "HGNC:427",
"url": "https://alliancegenome.org/gene/HGNC:427#orthology",
"database": "AGR"
},
{
"id": "ZFIN:ZDB-GENE-030616-115",
"url": "https://alliancegenome.org/gene/ZFIN:ZDB-GENE-030616-115#orthology",
"database": "AGR"
}
],
"glygen_name": "Zebrafish",
"common_name": "Zebrafish"
},
{
"uniprot_canonical_ac": "F8W3R9-1",
"protein_name": "ALK tyrosine kinase receptor",
"gene_name": "alk",
"tax_id": 7955,
"organism": "Danio rerio",
"sequence": {
"sequence": "MIARILYFFLWSAAFLPELQCASQRTADALTTFPTSAFINGTDRKDSNQTSTSRIKRKTLSVDFAVPSLLRYYLALFIKRPLNGDCLSFNGCYTVRANLLMRCVPLQKTIAGLLDAKLAAMNVNRSSTGQLPYRQKRPVPKVLNLGLTSASRKSNQVVVEVGEEMVKTGCGGLHVYEDAPVVFLEMDLTRILEWWLGAEGGRLRVRLMPERKVQVPGKEDKYSAAIRASDARLFIQIASSERPSSTISRNPTVAPKYWNFSWIAEDELTFPEDPVSTSDCTSKAKSCDRRPDGYYPEFAWSLTSAEDSWAIDQTMVKTKASSQGWEEGRFLTVNSSALTGPWVLSPWFRAAHRPCGLDITVFLHPRQSGRYTVWLIERDKPPLALLTTEHPHVIGWAVVHLSLAARSKPFRISSSYSQPGEIETATYDPRYSTNCTTRSSQNVTLRGRYHCRGGREINVSQLCDFSIDCPQGDDEGEHCRQFLNGSYCSFGREDCGWQPVQGRGPQWRAHPSIPQSLRSSCPSPGALLAIDSQPKGQRGSAQVRSPLFFYPLRNAPCMVKFWVCGSSNGALSLWITENSTGPEGQRSLWNSTSEANMGKGWKLITLPLFGLVDLFYLQFSADISSSSGIAFAVDNFTLSMECFLETNGEFPPVAPISPTQALFTQSNENIKTTTTLYGGPGASTESVKWIFHTCGATGQDGPTPTQCSNSYRNTNVNVTVGTKGPFKGIQMWQVPETRKYRITAYGAAGGRSVLAVHKSHGVYMTGDFLLQKDELLYILVGQEGEDACPNMVPTMDRICREQQGPSINKTQLKGGGGGGGGGTYVFKVVNGVHIPLLIAAGGGGRGYSSQSETPEEVMDRDPSIPGRNGKSGTAGGGGGWNDSAPVPQGGRPLILGGQGGEPCQAMGWKTRGGFGGGGGACTAGGGGGGYRGGSAWHDNDPRKDGDDGTSYISPDGEMYLEPLKGMEGNGEVIINPVQNCSHCESGDCHETSEGMVCYCDEELTLAPDGVSCINSTELPLLPAQPSLSHLALGLSVGTSALIAALLLAVSGVMIMYRRKHTELQSIQLELQSPDCKLSKLRASTIMTDYNPNYCFGGKTASVNDLKEVPRRNISLTRGLGHGAFGEVYEGLAVGIPGEPSPMQVAVKTLPEVCSEQDELDFLMEALIISKFSHQNIVRCIGVSLQALPHFILLELMAGGDLKSFLRETRPRLEHPSSLTMVDLLNIARDIARGCQYLEENQFIHRDIAARNCLLTCKGPGRVAKIGDFGMARDIYRASYYRKGGRAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSRSNQEVLEFVTNGGRMDPPKNCPGPVYRIMTQSWQHQPEDRPNFSTILERIDYCLQDPDVVNVPLPVEYGPIPEEEERVPMRPEDPSAPSLLVSPQGTEDVPSATHSAQSKKDGEAIHMANLSTDSKLPPVPPSQPHPHHHLQTPVVTAPVPASKPSSTTSNAQDGGHVNLGFMQAHSSEKESRNRKPTNLWNPTYGSWFLQQQQKRQQVQAQRQTSGPRIPGEGQEQVGRTVTVAEALGLQQQHKQQQYQQQLQRQQQQQQQQQQQQGLCRPLLPPPPPPAPTPLLLDSATLAPVPLYRLRRFPCGNIGYGYQEQGLPMEPMQGPQLPPPHPGQQRPISLTRASGPEDSRPLLVTMGTVQDSRLPKMEGHNATVL",
"length": 1705
},
"evidence": [
{
"id": "HGNC:427",
"url": "https://alliancegenome.org/gene/HGNC:427#orthology",
"database": "AGR"
},
{
"id": "RGD:628622",
"url": "https://alliancegenome.org/gene/RGD:628622#orthology",
"database": "AGR"
},
{
"id": "MGI:103305",
"url": "https://alliancegenome.org/gene/MGI:103305#orthology",
"database": "AGR"
},
{
"id": "ZFIN:ZDB-GENE-031027-1",
"url": "https://alliancegenome.org/gene/ZFIN:ZDB-GENE-031027-1#orthology",
"database": "AGR"
}
],
"glygen_name": "Zebrafish",
"common_name": "Zebrafish"
},
{
"uniprot_canonical_ac": "P08923-1",
"protein_name": "Leukocyte tyrosine kinase receptor",
"gene_name": "Ltk",
"tax_id": 10090,
"organism": "Mus musculus",
"sequence": {
"sequence": "MGCSHRLLLWLGAAGTILCSNSEFQTPFLTPSLLPVLVLNSQEQKVTPTPSKLEPASLPNPLGTRGPWVFNTCGASGRSGPTQTQCDGAYTGSSVMVTVGAAGPLKGVQLWRVPDTGQYLISAYGAAGGKGAQNHLSRAHGIFLSAVFFLRRGEPVYILVGQQGQDACPGGSPESQLVCLGESGEHATTYGTERIPGWRRWAGGGGGGGGATSIFRLRAGEPEPLLVAAGGGGRSYRRRPDRGRTQAVPERLETRAAAPGSGGRGGAAGGGSGWTSRAHSPQAGRSPREGAEGGEGCAEAWAALRWAAAGGFGGGGGACAAGGGGGGYRGGDTSESDLLWADGEDGTSFVHPSGELYLQPLAVTEGHGEVEIRKHPNCSHCPFKDCQWQAELWTAECTCPEGTELAVDNVTCMDLPTTASPLILMGAVVAALALSLLMMCAVLILVNQKCQGLWGTRLPGPELELSKLRSSAIRTAPNPYYCQVGLSPAQPWPLPPGLTEVSPANVTLLRALGHGAFGEVYEGLVTGLPGDSSPLPVAIKTLPELCSHQDELDFLMEALIISKFSHQNIVRCVGLSFRSAPRLILLELMSGGDMKSFLRHSRPHPGQLAPLTMQDLLQLAQDIAQGCHYLEENHFIHRDIAARNCLLSCSGASRVAKIGDFGMARDIYQASYYRKGGRTLLPVKWMPPEALLEGLFTSKTDSWSFGVLLWEIFSLGYMPYPGHTNQEVLDFIATGNRMDPPRNCPGPVYRIMTQCWQHQPELRPDFGSILERIQYCTQDPDVLNSPLPVEPGPILEEEEASRLGNRSLEGLRSPKPLELSSQNLKSWGGGLLGSWLPSGLKTLKPRCLQPQNIWNPTYGSWTPRGPQGEDTGIEHCNGSSSSSIPGIQ",
"length": 888
},
"evidence": [
{
"id": "ZFIN:ZDB-GENE-030616-115",
"url": "https://alliancegenome.org/gene/ZFIN:ZDB-GENE-030616-115#orthology",
"database": "AGR"
}
],
"glygen_name": "Mouse",
"common_name": "Mouse"
},
{
"uniprot_canonical_ac": "P29376-1",
"protein_name": "Leukocyte tyrosine kinase receptor",
"gene_name": "LTK",
"tax_id": 9606,
"organism": "Homo sapiens",
"sequence": {
"sequence": "MGCWGQLLVWFGAAGAILCSSPGSQETFLRSSPLPLASPSPRDPKVSAPPSILEPASPLNSPGTEGSWLFSTCGASGRHGPTQTQCDGAYAGTSVVVTVGAAGQLRGVQLWRVPGPGQYLISAYGAAGGKGAKNHLSRAHGVFVSAIFSLGLGESLYILVGQQGEDACPGGSPESQLVCLGESRAVEEHAAMDGSEGVPGSRRWAGGGGGGGGATYVFRVRAGELEPLLVAAGGGGRAYLRPRDRGRTQASPEKLENRSEAPGSGGRGGAAGGGGGWTSRAPSPQAGRSLQEGAEGGQGCSEAWATLGWAAAGGFGGGGGACTAGGGGGGYRGGDASETDNLWADGEDGVSFIHPSSELFLQPLAVTENHGEVEIRRHLNCSHCPLRDCQWQAELQLAECLCPEGMELAVDNVTCMDLHKPPGPLVLMVAVVATSTLSLLMVCGVLILVKQKKWQGLQEMRLPSPELELSKLRTSAIRTAPNPYYCQVGLGPAQSWPLPPGVTEVSPANVTLLRALGHGAFGEVYEGLVIGLPGDSSPLQVAIKTLPELCSPQDELDFLMEALIISKFRHQNIVRCVGLSLRATPRLILLELMSGGDMKSFLRHSRPHLGQPSPLVMRDLLQLAQDIAQGCHYLEENHFIHRDIAARNCLLSCAGPSRVAKIGDFGMARDIYRASYYRRGDRALLPVKWMPPEAFLEGIFTSKTDSWSFGVLLWEIFSLGYMPYPGRTNQEVLDFVVGGGRMDPPRGCPGPVYRIMTQCWQHEPELRPSFASILERLQYCTQDPDVLNSLLPMELGPTPEEEGTSGLGNRSLECLRPPQPQELSPEKLKSWGGSPLGPWLSSGLKPLKSRGLQPQNLWNPTYRS",
"length": 864
},
"evidence": [
{
"id": "ZFIN:ZDB-GENE-030616-115",
"url": "https://alliancegenome.org/gene/ZFIN:ZDB-GENE-030616-115#orthology",
"database": "AGR"
}
],
"glygen_name": "Human",
"common_name": "Human"
},
{
"uniprot_canonical_ac": "P97793-1",
"protein_name": "ALK tyrosine kinase receptor",
"gene_name": "Alk",
"tax_id": 10090,
"organism": "Mus musculus",
"sequence": {
"sequence": "MGAAGFLWLLPPLLLAAASYSGAATDQRAGSPASGPPLQPREPLSYSRLQRKSLAVDFVVPSLFRVYARDLLLPQPRSPSEPEAGGLEARGSLALDCEPLLRLLGPLPGISWADGASSPSPEAGPTLSRVLKGGSVRKLRRAKQLVLELGEETILEGCIGPPEEVAAVGILQFNLSELFSWWILHGEGRLRIRLMPEKKASEVGREGRLSSAIRASQPRLLFQIFGTGHSSMESPSETPSPPGTFMWNLTWTMKDSFPFLSHRSRYGLECSFDFPCELEYSPPLHNHGNQSWSWRHVPSEEASRMNLLDGPEAEHSQEMPRGSFLLLNTSADSKHTILSPWMRSSSDHCTLAVSVHRHLQPSGRYVAQLLPHNEAGREILLVPTPGKHGWTVLQGRVGRPANPFRVALEYISSGNRSLSAVDFFALKNCSEGTSPGSKMALQSSFTCWNGTVLQLGQACDFHQDCAQGEDEGQLCSKLPAGFYCNFENGFCGWTQSPLSPHMPRWQVRTLRDAHSQGHQGRALLLSTTDILASEGATVTSATFPAPMKNSPCELRMSWLIRGVLRGNVSLVLVENKTGKEQSRTVWHVATDEGLSLWQHTVLSLLDVTDRFWLQIVTWWGPGSRATVGFDNISISLDCYLTISGEEKMSLNSVPKSRNLFEKNPNKESKSWANISGPTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVVVGSEGPLKGVQIWKVPATDTYSISGYGAAGGKGGKNTMMRSHGVSVLGIFNLEKGDTLYILVGQQGEDACPRANQLIQKVCVGENNVIEEEIRVNRSVHEWAGGGGGGGGATYVFKMKDGVPVPLIIAAGGGGRAYGAKTETFHPERLESNSSVLGLNGNSGAAGGGGGWNDNTSLLWAGKSLLEGAAGGHSCPQAMKKWGWETRGGFGGGGGGCSSGGGGGGYIGGNAASNNDPEMDGEDGVSFISPLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLADDGVSCIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQALPRFILLELMAGGDLKSFLRETRPRPNQPTSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGAGRIAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPVVEEEEKVPMRPKDPEGMPPLLVSPQPAKHEEASAAPQPAALTAPGPSVKKPPGAGAGAGAGAGAGPVPRGAADRGHVNMAFSQPNPPPELHKGPGSRNKPTSLWNPTYGSWFTEKPAKKTHPPPGAEPQARAGAAEGGWTGPGAGPRRAEAALLLEPSALSATMKEVPLFRLRHFPCGNVNYGYQQQGLPLEATAAPGDTMLKSKNKVTQPGP",
"length": 1621
},
"evidence": [
{
"id": "HGNC:427",
"url": "https://alliancegenome.org/gene/HGNC:427#orthology",
"database": "AGR"
},
{
"id": "RGD:628622",
"url": "https://alliancegenome.org/gene/RGD:628622#orthology",
"database": "AGR"
},
{
"id": "MGI:103305",
"url": "https://alliancegenome.org/gene/MGI:103305#orthology",
"database": "AGR"
},
{
"id": "ZFIN:ZDB-GENE-031027-1",
"url": "https://alliancegenome.org/gene/ZFIN:ZDB-GENE-031027-1#orthology",
"database": "AGR"
},
{
"id": "Q9UM73",
"url": "https://omabrowser.org/oma/group/Q9UM73/",
"database": "OMA"
}
],
"glygen_name": "Mouse",
"common_name": "Mouse"
}
],
"go_annotation": {
"categories": [
{
"name": "Molecular Function",
"total": 7,
"go_terms": [
{
"name": "protein tyrosine kinase activity",
"id": "GO:0004713",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0004713",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "ATP binding",
"id": "GO:0005524",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005524",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "heparin binding",
"id": "GO:0008201",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0008201",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "identical protein binding",
"id": "GO:0042802",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0042802",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "receptor signaling protein tyrosine kinase activator activity",
"id": "GO:0030298",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0030298",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "transmembrane receptor protein tyrosine kinase activity",
"id": "GO:0004714",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0004714",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "protein kinase activity",
"id": "GO:0004672",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0004672",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
}
]
},
{
"name": "Cellular Component",
"total": 4,
"go_terms": [
{
"name": "plasma membrane",
"id": "GO:0005886",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005886",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "receptor complex",
"id": "GO:0043235",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0043235",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "extracellular exosome",
"id": "GO:0070062",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0070062",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "protein-containing complex",
"id": "GO:0032991",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0032991",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
}
]
},
{
"name": "Biological Process",
"total": 12,
"go_terms": [
{
"name": "signal transduction",
"id": "GO:0007165",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0007165",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "cell surface receptor protein tyrosine kinase signaling pathway",
"id": "GO:0007169",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0007169",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "peptidyl-tyrosine autophosphorylation",
"id": "GO:0038083",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0038083",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "regulation of cell population proliferation",
"id": "GO:0042127",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0042127",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "negative regulation of lipid catabolic process",
"id": "GO:0050995",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0050995",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "energy homeostasis",
"id": "GO:0097009",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0097009",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "regulation of neuron differentiation",
"id": "GO:0045664",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045664",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "protein autophosphorylation",
"id": "GO:0046777",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0046777",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "phosphorylation",
"id": "GO:0016310",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0016310",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "regulation of apoptotic process",
"id": "GO:0042981",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0042981",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "neuron development",
"id": "GO:0048666",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:0048666",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
},
{
"name": "positive regulation of dendrite development",
"id": "GO:1900006",
"url": "https://www.ebi.ac.uk/QuickGO/term/GO:1900006",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
}
],
"pmid": ""
}
]
}
]
},
"pro_annotation": [],
"site_annotation": [
{
"start_pos": 1115,
"end_pos": 1117,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 169,
"end_pos": 171,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 244,
"end_pos": 246,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 285,
"end_pos": 287,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 324,
"end_pos": 326,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 411,
"end_pos": 413,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 424,
"end_pos": 426,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 445,
"end_pos": 447,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 563,
"end_pos": 565,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 571,
"end_pos": 573,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 627,
"end_pos": 629,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 709,
"end_pos": 711,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 808,
"end_pos": 810,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 863,
"end_pos": 865,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 864,
"end_pos": 866,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 886,
"end_pos": 888,
"annotation": "n_glycosylation_sequon"
},
{
"start_pos": 986,
"end_pos": 988,
"annotation": "n_glycosylation_sequon"
}
],
"ptm_annotation": [
{
"annotation": "N-glycosylated.",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
},
{
"database": "PubMed",
"id": "9174053",
"url": "https://glygen.org/publication/PubMed/9174053"
}
]
},
{
"annotation": "Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity (PubMed:11121404, PubMed:15938644, PubMed:16878150, PubMed:34819673). In cells not stimulated by a ligand, receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) dephosphorylates ALK at the sites in ALK that are undergoing autophosphorylation through autoactivation (PubMed:17681947). Phosphorylation at Tyr-1507 is critical for SHC1 association (PubMed:17274988).",
"evidence": [
{
"database": "UniProtKB",
"id": "Q9UM73",
"url": "https://www.uniprot.org/uniprotkb/Q9UM73"
},
{
"database": "PubMed",
"id": "16878150",
"url": "https://glygen.org/publication/PubMed/16878150"
},
{
"database": "PubMed",
"id": "17274988",
"url": "https://glygen.org/publication/PubMed/17274988"
},
{
"database": "PubMed",
"id": "15938644",
"url": "https://glygen.org/publication/PubMed/15938644"
},
{
"database": "PubMed",
"id": "17681947",
"url": "https://glygen.org/publication/PubMed/17681947"
},
{
"database": "PubMed",
"id": "34819673",
"url": "https://glygen.org/publication/PubMed/34819673"
},
{
"database": "PubMed",
"id": "11121404",
"url": "https://glygen.org/publication/PubMed/11121404"
}
]
}
],
"interactions": [],
"reactions": [
{
"id": "10596",
"name": "",
"equation": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)",
"summary": "",
"cellular_location": "",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"P00519-1",
"Q07912-1",
"P42684-1",
"P10721-1",
"P08069-1",
"P06239-1",
"O15146-1",
"Q9UF33-1",
"P08922-1",
"Q9UM73-1",
"P42679-1",
"Q12866-1",
"P07947-1",
"P51451-1",
"P49760-1",
"P49761-1",
"Q9HAZ1-1",
"Q06187-1",
"P49759-1",
"P51813-1",
"P07333-1",
"Q9UIG0-1",
"Q6XUX3-1",
"P22607-1",
"P00533-1",
"Q9Y463-1",
"P29317-1",
"P21802-1",
"Q9NR20-1",
"Q13627-1",
"P11362-1",
"P42685-1",
"Q16832-1",
"Q15375-1",
"P29323-1",
"P22455-1",
"P16591-1",
"P07332-1",
"P29322-1",
"P54756-1",
"P29320-1",
"Q08345-1",
"Q92630-1",
"Q05397-1",
"P54753-1",
"Q15303-1",
"P36888-1",
"P09769-1",
"P04626-1",
"P21860-1",
"Q14289-1",
"O43781-1",
"P54764-1",
"P19525-1",
"P21709-1",
"P54762-1",
"P54760-1",
"P06241-1",
"P07948-1",
"P52333-1",
"P06213-1",
"P14616-1",
"Q05655-1",
"Q08881-1",
"P29376-1",
"P23458-1",
"P08581-1",
"Q14680-1",
"P43405-1",
"O60674-1",
"P08631-1",
"P46734-1",
"P45985-1",
"Q02750-1",
"P52564-1",
"O14733-1",
"Q13163-1",
"P09619-1",
"Q16288-1",
"P36507-1",
"Q16620-1",
"Q504Y2-1",
"P16234-1",
"Q13882-1",
"P04629-1",
"Q01974-1",
"Q06418-1",
"P07949-1",
"Q96KB5-1",
"Q15569-1",
"Q96S53-1",
"Q6J9G0-1",
"P42680-1",
"P35916-2",
"P0C1S8-1",
"P17948-1",
"P42681-1",
"P35590-1",
"Q13470-1",
"P33981-1",
"P12931-1",
"P35968-1",
"P30530-1",
"P43403-1",
"P29597-1",
"O75716-1",
"Q04912-1",
"Q02763-1",
"Q9H3Y6-1",
"P30291-1",
"O43353-1",
"P35790-1",
"P14618-1",
"Q8IVH8-1",
"Q9NZJ5-1",
"Q5JZY3-1",
"Q13043-1",
"P42345-1",
"P41240-1"
],
"evidence": [
{
"id": "10596",
"database": "Rhea",
"url": "https://www.rhea-db.org/rhea/10596"
}
]
},
{
"id": "R-HSA-201486",
"name": "ALK binds ligand pleiotrophin (PTN)",
"equation": "",
"summary": "Pleiotrophin (PTN) is a secreted growth factor that induces neurite outgrowth. The receptor tyrosine kinase anaplastic lymphoma kinase (ALK) binds PTN and transduces PTN-mediated signals through RAS, PI3K, PLCG1 and IRS1 (Stoica et al. 2001, Bowden et al. 2002), as well as through GSK3B/CTTNB1 (Yanagisawa et al. 2010).",
"cellular_location": "extracellular region, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-201486",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-201486"
}
]
},
{
"id": "R-HSA-201510",
"name": "PI3K synthesizes PIP3 downstream of ALK",
"equation": "",
"summary": "PI3K phosphorylates PIP2 to PIP3 downstream of activated ALK, leading to activation of the AKT pathway as assessed by S473 phosphorylation (Bai et al, 2000; Slupianek et al, 2001; Slupianek et al, 2004; Chen et al, 2008). AKT signaling contributes to apoptotic escape and cellular proliferation through regulation of proteins such as CDKN1B/p27, CCND2 and BCL2L11/BIM, among others (Gu et al, 2004; Rassidakis et al, 2005; Marzec et al, 2007; reviewed in Chiarle et al, 2008).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"P42336-1",
"Q9UM73-1",
"P42338-1"
],
"evidence": [
{
"id": "R-HSA-201510",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-201510"
}
]
},
{
"id": "R-HSA-201515",
"name": "Active ALK recruits PI3K",
"equation": "",
"summary": "Activated ALK in the form of NPM-ALK recruits PI3K. Binding of PI3K to ALK is probably mediated by an adaptor protein that has not yet been identified (Bai et al, 2000; Slupianek et al, 2001; reviewed in Chiarle et al, 2008). Consistent with studies with the NPM-ALK fusion protein, recruitment of PI3K to ALK has also been demonstrated downstream of PTN activation, and phosphorylation of AKT is observed after ALK stimulation with MDK (Stoica et al, 2001; Stoica et al, 2002). In contrast, demonstration of PI3K activation downstream of ALKAL1 or 2 binding has not been demonstrated to date.
",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"P42336-1",
"Q9UM73-1",
"P42338-1"
],
"evidence": [
{
"id": "R-HSA-201515",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-201515"
}
]
},
{
"id": "R-HSA-201519",
"name": "ALK:PTN dimerization",
"equation": "",
"summary": "Binding of PTN is believed to induce ALK receptor dimerization, similar to other receptor tyrosine kinases (reviewed in Roskoski, 2013; Della Corte et al, 2018). Consistent with this, studies in rat with enforced dimerization of ALK lead to receptor activation, downstream signaling and neurite outgrowth in PC12 cells (Gouzi et al, 2005).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-201519",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-201519"
}
]
},
{
"id": "R-HSA-201521",
"name": "ALK autophosphorylation",
"equation": "",
"summary": "ALK1 is phosphorylated on tyrosine residues in intracellular domain after ligand binding and dimerization, consistent with other receptor tyrosine kinases (Soutto et al, 2001; Stoica et al, 2002; Perez-Pinera et al, 2007; Lee et al, 2010; reviewed in Roskoski, 2013; Della Corte et al, 2018). ALK1, like other members of the insulin receptor subfamily, has a YXXXXYY motif in the activation loop. Trans-phosphorylation of the three tyrosine residues in the activation (Y1278, Y1282 and Y1283) after ligand binding causes a conformational change that relieves autoinhibition of the kinase (Donella-Deana et al, 2005; Tartari et al, 2007; Lee et al, 2010; reviewed in Roskoski et al, 2013). ALK also contains a number of tyrosine residues in the juxtamembrane domain region, at positions 1078, 1092, 1096, 1131, 1358, 1507 and 1604, among others (Rush et al, 2005; Kuo et al, 2007; Degoutin et al, 2007; reviewed in Roskoski, 2013). Whether phosphorylation of these residues precedes activation loop phosphorylation, as is the case for other RTKs, remains to be investigated. In addition, some sites may be phosphorylated by other cellular kinases after ALK auto-phosphorylation (reviewed in Klug et al, 2018; Roskoski, 2013).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-201521",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-201521"
}
]
},
{
"id": "R-HSA-9667914",
"name": "ALK binds ligand midkine (MDK)",
"equation": "",
"summary": "ALK receptor tyrosine kinase binds to secreted growth factor midkine (MDK), homologous to pleiotrophin (PTN) (Stoica et al, 2002). MDK activates PI3K signaling (Stoica et al. 2002) and IRS1/NFKB signaling (Kuo et al, 2007) downstream of ALK.",
"cellular_location": "extracellular region, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9667914",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9667914"
}
]
},
{
"id": "R-HSA-9700114",
"name": "NVP-TAE684-resistant ALK mutants don't bind NVP-TAE684",
"equation": "",
"summary": "The following ALK mutants are resistant to inhibiton by NVP-TAE684
ALK L1152R: Sasaki et al, 2011
ALK T1171N: Ceccon et al, 2013
ALK L1198P: Heuckmann et al, 2011
ALK D1203N: Heuckmann et al, 2011
ALK A1234T: George et al, 2008
",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700114",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700114"
}
]
},
{
"id": "R-HSA-9700131",
"name": "ALK mutants bind type I TKIs",
"equation": "",
"summary": "The following ALK mutants and fusion proteins are sensitive to these type I tyrosine kinase inhibitors:
crizotinib:
ALK F1174V: Ceccon et al, 2015
ALK L1198F: Chuang et al, 2019; Ceccon et al, 2015
BCL11A(1-219)InsDHPPA-ALK(1058-1620): Tian et al, 2017
BIRC6(1-958)-ALK(1058-1620): Shan et al, 2015
EIF2AK3(30-144)-ALK(1058-1620): Ali et al, 2016
EML4(1-223)-ALK(1059-1620): Ali et al, 2016
EML4(1-223)insKMSTREKNSQV-ALK(1059-1620): Ali et al, 2016
EML4(1-486)-ALK(1058-1620): Ali et al, 2016; Hrustanovic et al, 2015; Katayama et al, 2011
FN1(32-1201)-ALK(1022-1620): Ren et al, 2012
HIP1(1-1019)-ALK(1058-1620): Ou et al, 2014
HIP1(1-963)-ALK(1058-1620): Hong et al, 2014
HIP1(1-719)InsL-ALK(1059-1620): Fang et al, 2014
NPM1(1-117)-ALK(1058-1620): Prokoph et al, 2020
PPM1B (1-282)-ALK(1058-1620): Ali et al, 2016
PRKAR1A(1-183)-ALK(1058-1620): Ali et al, 2016
STRN(1-137)-ALK(1058-1620): Kelly et al, 2014
NVP-TAE684:
ALK F1174L: George et al, 2008; Heuckmann et al, 2011
ALK V1180L: Katayama et al, 2014
ALK L1196M: Heuckmann et al, 2011
ALK L1196Q: Ceccon et al, 2013
ALK G1269S: Heuckmann, 2011
ALK R1275Q: George, 2008
CLTC(2-1634)-ALK(1059-1620): Cerchietti et al, 2011
EML4(1-223)insKMSTREKNSQV -ALK(1059-1620): Heuckmann, 2011
FN1(32-1201)-ALK(1022-1620): Ren et al, 2012
NPM1(1-117)-ALK(1058-1620): Galkin et al, 2007
STRN(1-137)-ALK(1058-1620): Kelly et al, 2014
ceritinib:
ALK I1171T: Friboulet et al, 2014; Katayama et al, 2014
ALK F1174V: Ceccon et al, 2015
ALK V1180L: Katayama et al, 2014
ALK S1206Y: Friboulet et al, 2014;
ALK G1269A: Friboulet et al, 2014;
EML4(1-486)-ALK(1058-1620): Hrustanovic et al, 2015
brigatinib:
ALK F1174V: Ceccon et al, 2015
ALK V1180L: Katayama et al, 2014
ALK L1196Q: Ceccon et al, 2013
NPM1(1-117)-ALK(1058-1620): Ceccon et al, 2015
alectinib:
ALK F1174I: Ou et al, 2016
ALK F1174L: Ou et al, 2016
ALK F1174V: Ou et al, 2016; Ceccon et al, 2015 (moderate)
EML4(1-223)-ALK(1059-1620): Ou et al, 2014
EML4(1-223)insKMSTREKNSQV-ALK(1059-1620): Ou et al, 2014
EML4(1-486)-ALK(1058-1620): Davare et al, 2015
HIP1(1-1019)-ALK(1058-1620):Ou et al, 2014
ASP3026:
ALK V1180L: Katayama et al, 2014
Entrectinib:
ALK C1156Y: Ardini et al, 2016
ALK L1196M: Ardini et al, 2016
EML4(1-223)-ALK(1059-1620): Ardini et al, 2016
EML4(1-223)insKMSTREKNSQV-ALK(1059-1620): Ardini et al, 2016
EML4(1-486)-ALK(1058-1620): Ardini et al, 2016
NPM1(1-117)-ALK(1058-1620): Ardini et al, 2016
",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [
"R-ALL-9699973"
],
"output_participant_list": [
"R-HSA-9700014"
],
"enzyme_list": [
"Q9UM73-1",
"O75688-1",
"Q9NR09-1",
"Q9NZJ5-1"
],
"evidence": [
{
"id": "R-HSA-9700131",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700131"
}
]
},
{
"id": "R-HSA-9700137",
"name": "ALK:MDK dimerization",
"equation": "",
"summary": "Binding of MDK is believed to induce ALK receptor dimerization, similar to other receptor tyrosine kinases (reviewed in Roskoski, 2013; Della Corte et al, 2018). Consistent with this, studies in rat with enforced dimerization of ALK lead to receptor activation, downstream signaling and neurite outgrowth in PC12 cells (Gouzi et al, 2005).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700137",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700137"
}
]
},
{
"id": "R-HSA-9700142",
"name": "Active ALK binds FRS2",
"equation": "",
"summary": "The adaptor protein FRS2 binds activated ALK as assessed with studies using full-length wild-type ALK as well as the NPM1-ALK fusion (Degoutin et al, 2007; Chikamori et al, 2007). Recruitment and activation of FRS2 does not depend on the juxtamembrane domain or any of the identified phosphotyrosine binding (PTB) NXXpY sites of ALK, and the binding site remains to be determined (Chikamori et al, 2007; Degoutin et al, 2007).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700142",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700142"
}
]
},
{
"id": "R-HSA-9700149",
"name": "Active ALK binds PLCG1",
"equation": "",
"summary": "Based on studies with the oncogenic NPM-ALK fusion, ALK is predicted to signal through the PLC gamma signaling pathway. PLCG1 binds to phosphorylated tyrosine 1604 on the activated receptor. PLCG1 signaling contributes to mitogenesis and cellular proliferation downstream of ALK signaling (Bai et al, 1998; reviewed in Turner and Alexander, 2006; Chiarle et al, 2008).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"P19174-1",
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700149",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700149"
}
]
},
{
"id": "R-HSA-9700154",
"name": "Active ALK binds SHC1",
"equation": "",
"summary": "SHC1 is recruited to the full-length ALK receptor after activation (Motegi et al, 2004; Degoutin et al, 2007; Kuo et al, 2007). The p46 and p52 isoforms of SHC1 bind to ALK phospho-tyrosine 1507 in a manner that depends on ALK kinase activity (Degoutin et al, 2007). SHC recruitment contributes to activation of MAP kinase signaling and cellular proliferation downstream of ALK signaling, as well as neurite outgrowth and differentiation in PC-12 cells (Souttou et al, 2001; Motegi et al, 2004; Moog-Lutz et al, 2005; Gouzi et al, 2005; Degoutin et al, 2007; reveiwed in Turner and Alexander, 2006; Chiarle et al, 2009).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700154",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700154"
}
]
},
{
"id": "R-HSA-9700156",
"name": "Active ALK dimer binds IRS1",
"equation": "",
"summary": "Phosphorylated tyrosine 1096 is the docking site for IRS1 on the active full length- ALK receptor. IRS-mediated signaling simulates the MAP kinase and PI3K pathways and contributes to cellular proliferation in a manner that depends on ALK kinase activity (Motegi et al, 2004; Kuo et al, 2007; reviewed in Turner and Alexander, 2006; Roskoski, 2013; Della Corte et al, 2018).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700156",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700156"
}
]
},
{
"id": "R-HSA-9700164",
"name": "Active ALK phosphorylates FRS2",
"equation": "",
"summary": "FRS2 is phosphorylated downstream of ALK in a manner that depends on ALK kinase activity (Degoutin et al, 2007).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700164",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700164"
}
]
},
{
"id": "R-HSA-9700168",
"name": "Active ALK phosphorylates IRS1",
"equation": "",
"summary": "IRS1 is phosphorylated downstream of active ALK in a manner that is dependent on ALK kinase activity. Based on studies in NPM-ALK fusions, ALK likely phosphorylates IRS1 on one or more tyrosine residues, but the target amino acid(s) have not been identified directly in the context of the full-length ALK receptor (Fujimoto et al 1996; Stoica et al, 2001; Motegi et al, 2004; reviewed in Roskoski, 2013; Delle Corte et al, 2018). ALK-dependent IRS1 phosphorylation activates the MAP kinase signaling pathway and promotes cellular proliferation, but direct binding of a RAS GEF such as GRB2:SOS1 has not been shown (reviewed in Turner and Alexander, 2006; Chiarle et al, 2008; Roskoski, 2013).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700168",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700168"
}
]
},
{
"id": "R-HSA-9700171",
"name": "Active ALK phosphorylates PLCG1",
"equation": "",
"summary": "Based on studies with the NPM-ALK fusion, ALK is predicted to phosphorylate PLCG downstream of dimerization and autophosphorylation. PLCG signaling contributes to cellular proliferation downstream of ALK, and mutation of the ALK PLCG binding site eliminates the growth-factor independent transformation of Ba/F3 cells (Bai et al, 1998; reviewed in Chiarle et al, 2008; Palmer et al, 2009).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"P19174-1",
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700171",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700171"
}
]
},
{
"id": "R-HSA-9700175",
"name": "Active ALK phosphorylates SHC1",
"equation": "",
"summary": "SHC1 is phosphorylated downstream of active ALK in a manner that depends on ALK kinase activity (Degoutin et al, 2007). SHC signaling downstream of the ALK receptor contributes to MAP kinase signaling and cellular proliferation and differentiation (Degoutin et al, 2007; Motegi et al, 2004; reviewed in Turner and Alexander, 2006; Chiarle et al, 2008; Roskoski, 2013). The exact sites of SHC1 phosphorylation in the context of ALK signaling have not been explicitly demonstrated, but are presumed to be the canonical tyrosine phosphorylation sites of active SHC1 (reviewed in Ravichandran, 2001).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700175",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700175"
}
]
},
{
"id": "R-HSA-9700184",
"name": "Ligand-independent dimerization of point mutants of ALK",
"equation": "",
"summary": "In addition to activation by translocations that lead to the formation of ALK fusion proteins, the ALK locus is also subject to activating point mutations (reviewed in Roskoski, 2013; Hallberg and Palmer, 2016; Della Corte et al, 2018). ALK mutations are most prevalent in neuroblastoma, where they are present in 7% of sporadic and up to 50% of familial cases, but also occur at lower frequencies in non-small cell lung cancer, anaplastic thyroid cancer among other cancers (Mosse et al, 2008; Chand et al, 2013; Schonherr et al, 2011; George et al, 2008; Janoueix-Lerousy et al, 2008; reviewed in Della Corte et al, 2018). Missense mutations tend to cluster in the kinase domain, but are also found in the juxtamembrane and extracellular regions (Chen et al, 2008; Murugan et al, 2011; Wang et al, 2011). Activating mutations have been shown in several cases to lead to ligand-independent dimerization and activation, and to promote oncogenic transformation in vitro and in vivo, while some ALK mutations identified in cancers retain dependence on ligand binding (Chand et al, 2008; Schonherr et al, 2011; Chen et al, 2008; George et al, 2008; Mosse et al, 2008; Ceccon et al, 2013; Ceccon et al, 2015; Murugan et al, 2011; Wang et al, 2011; reviewed in Della Corte et al, 2018).",
"cellular_location": "plasma membrane",
"input_participant_list": [
"R-HSA-9700567"
],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700184",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700184"
}
]
},
{
"id": "R-HSA-9700186",
"name": "Autophosphorylation of point mutants of ALK",
"equation": "",
"summary": "Oncogenic point mutations in ALK promote ligand-independent transautophosphorylation, leading to constitutive downstream signaling though pathways such as the MAP kinase, PI3K-AKT, PLC gamma and STAT3 cascades (Chen et al, 2008; Mosse et al, 2008; George et al, 2008; Wang et al, 2011; Ceccon et al, 2013; Ceccon et al, 2015; reviewed in Hallberg and Palmer, 2013; Della Corte et al, 2018).",
"cellular_location": "plasma membrane",
"input_participant_list": [
"R-HSA-9700436"
],
"output_participant_list": [
"R-HSA-9700566"
],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700186",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700186"
}
]
},
{
"id": "R-HSA-9700190",
"name": "ALK mutants bind SHC",
"equation": "",
"summary": "Early studies with the NPM-ALK fusion identified two putative consensus sequences for phosphotyrosine binding proteins such as SHC. Coimmunoprecipitation studies in NIH 3T3 cells determined that the predominant SHC binding site is at tyrosine 567 (equivalent to Y1507 in the full length protein). SHC is tyrosine phosphorylated and associated with both NPM-ALK and GRB2 in these cells (Fujimoto et al, 1996). SHC has also been demonstrated to be a target of ALK-mediated phosphorylation in ALK-amplified neuroblastoma cells (Miyake et al, 2002). Mutation of the Y567 binding site to F abrogates the binding of SHC to the fusion protein, but does not eliminate the transforming activity of the protein, suggesting that SHC binding is not essential to cellular transformation (Fujimoto et al, 1996). SHC has also been shown to bind to other ALK fusions, including those with TFG, ATIC and FN1 and to contribute to signaling and transformation to various extents (Hernandez et al, 2002; Trinei et al, 2000; Ren et al, 2012; Okubo et al, 2012; Cazes et al, 2013reviewed in Hallberg and Palmer, 2013; Hallberg and Palmer, 2016; Roskoski, 2013)",
"cellular_location": "cytosol",
"input_participant_list": [
"R-HSA-9713538"
],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700190",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700190"
}
]
},
{
"id": "R-HSA-9700193",
"name": "ALK mutants phosphorylate SHC1",
"equation": "",
"summary": "SHC is tyrosine phosphorylated downstream of ALK fusion proteins. SHC may stimulate signaling through the MAP kinase cascade by virtue of its interaction with GRB2. The relative importance of this pathway to the oncogenic properties varies somewhat among different fusion proteins (Fujimoto et al, 1996; Trinei et al, 2000; Hernandez et al, 2002; Ren et al, 2012; reviewed in Hallberg and Palmer, 2013; Hallberg and Palmer, 2016).",
"cellular_location": "cytosol",
"input_participant_list": [
"R-HSA-9700015"
],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700193",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700193"
}
]
},
{
"id": "R-HSA-9700200",
"name": "PTPRZ dephosphorylates ligand-bound ALK dimers",
"equation": "",
"summary": "ALK is dephosphorylated by PTPRZ leading to loss of activity (Perez-Pinera et al, 2007).
Some studies suggest that, rather than being canonically activated by direct binding of PTN and MDK, ALK is activated in a ligand-independent manner by the binding of these ligands to PTPRZ (and possibly PTPRB) instead. PTN- and MDK-binding to PTPRZ/B promotes their oligomerization and catalytic inactivation, thus inhibiting the phosphatase activity and allowing the autoactivation of ALK to predominate (Perez-Pinera et al, 2007; Fukada et al, 2006; Maeda et al, 1999; Kuboyama et al, 2016; reviewed in Deuel, 2013). Discrepancies between these two models remain to be worked out.",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1",
"P23471-1"
],
"evidence": [
{
"id": "R-HSA-9700200",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700200"
}
]
},
{
"id": "R-HSA-9700646",
"name": "ASP-3026- resistant ALK mutants don't bind ASP-3026",
"equation": "",
"summary": "The following ALK mutants are resistant to inhibition by ASP-3026:
ALK T1551M: Amin et al 2016
ALK I1171S: Amin et al 2016
ALK I1171T: Katayama et al, 2014
ALK F1174L: Amin et al, 2016 (moderate)
ALKR 1192P: Amin et al, 2016
ALK G1269A: Amin et al, 2016 (moderate)",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700646",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700646"
}
]
},
{
"id": "R-HSA-9700647",
"name": "Active ALK phosphorylates SRC",
"equation": "",
"summary": "SRC is phosphorylated on tyrosine 419 and tyrosine 216 downstream of activated ALK (Cussac et al, 2004). SRC signaling contributes to cellular proliferation, potentially through GRB2-SOS1 mediated RAS activation, although this has not been explicitly demonstrated (Cussac et al, 2004; reviewed in Chiarle et al, 2008; Palmer et al, 2009).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700647",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700647"
}
]
},
{
"id": "R-HSA-9700648",
"name": "Active ALK binds SRC",
"equation": "",
"summary": "Based on studies with the oncogenic fusion protein NPM-ALK, SRC (and potentially other SRC-family members) binds to activated ALK receptor. Binding depends on tyrosine residue 1358 and ALK kinase activity, identifying pY1358 as the SRC-binding site (Cussac et al, 2004). SRC signaling downstream of ALK contributes to cellular proliferation (Cussac et al, 2004; reviewed in Chiarle et al, 2008; Palmer et al, 2009).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700648",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700648"
}
]
},
{
"id": "R-HSA-9700656",
"name": "alectinib resistant ALK mutants don't bind alectinib",
"equation": "",
"summary": "The following ALK mutants show resistance to alectinib:
ALK L1122V: Ceccon et al, 2015
ALK I1171N: Toyokawa et al, 2014; Ou et al, 2014; Gainor et al, 2016
ALK I1171S: Gainor et al 2016; Ou et al, 2014; Ou et al, 2016
ALK I1171T: Gainor et al, 2016; Ou et al, 2014; Zdzalik et al, 2014; Katayama et al, 2014
ALK F1174C: Ou et al, 2016
ALK V1180L: Katayama et al, 2014
ALK L1196M: Ceccon et al, 2015 (moderate); Gainor et al, 2016
ALK L1198F: Ceccon et al, 2015
ALK G1202R: Makimoto et al, 2019; Lin et al, 2016; Gainor et al, 2016
ALK S1206C: Ceccon et al, 2015
",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700656",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700656"
}
]
},
{
"id": "R-HSA-9700658",
"name": "ceritinib-resistant ALK mutants don't bind ceritinib",
"equation": "",
"summary": "The following ALK mutants are resistant to inhibition by ceritinib:
ALK L1122V: Ceccon et al, 2015
ALK I1171S: Amin et al, 2016
ALK F1174C: Gainor et al, 2016; Friboulet et al, 2014
ALK F1174L: Gainor et al, 2016; Wang et al, 2017
ALK F1174V: Friboulet et al, 2014
ALK L1196M: Friboulet et al, 2014; Gainor et al, 2016; Ceccon et al, 2015
ALK L1198F: Ceccon et al, 2015
ALK G1202R: Gainor et al, 2016; Friboulet et al, 2014; Lee et al, 2019
ALK D1203N: Wang et al, 2017
ALK S1206C: Ceccon et al, 2015
ALK G1269A: Friboulet et al, 2014
",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700658",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700658"
}
]
},
{
"id": "R-HSA-9700662",
"name": "Liganded-ALK dimer binds type I ALK-binding TKIs",
"equation": "",
"summary": "ALK can be bound and inhibited by type I tyrosine kinase inhibitors. Type I inhibitors bind in the ATP-binding site of the active conformation and prevent activation of the kinase (reviewed in Klug et al 2018; Roskoski, 2013). Crizotinib was one the first ALK inhibitors to be approved for use in ALK+ cancers (reviewed in Rodig et al, 2010; Ou et al, 2011; Gambacorti et al, 2011). Accumulation of secondary mutations leads to acquired crizotinib resistance and has prompted the development of second-and third generation inhibitors such as ceritinib, alectinib, brigatinib and lorlatinib, among others (Ou et al, 2014; Ou et al, 2016; Shaw et al, 2015; Ceccon et al, 2013; Ceccon et al, 2015; Zhang et al, 2016; Shaw et al, 2014; Recondo et al, 2020; Galkin et al, 2006; reviewed in Della Corte et al, 2018). Resistance to ALK inhibitors has also been reported in the context of bypass tracks including activation of pim1 in neuroblastoma, IL10R-STAT3 in ALCL and EGFR in NSCLC (Trigg et al, 2019, Prokoph et al, 2020, Lin et al, 2017).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [
"R-HSA-9700592"
],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9700662",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9700662"
}
]
},
{
"id": "R-HSA-9701485",
"name": "Active ALK binds JAK3",
"equation": "",
"summary": "Based on studies with NPM-ALK fusion proteins, ALK appears to signal through JAK3 in a manner that depends on JAK3-ALK binding (Zamo et al, 2002; Amin et al, 2003; Lai et al, 2005). When co-expressed in HEK293 cells, JAK3 binds to residues corresponding to 1058 to 1077 of the full length ALK receptor (Zamo et al, 2002). Although JAK3 often signals through recruitment and phosphorylation of STAT3, it is unclear whether STAT3 activation downstream of ALK depends on JAK3 (Zamo et al, 2002; Amin et al, 2003; Marzec et al, 2005; Han et al, 2006 a,b; Lai et al, 2005; Shi et al, 2006; reviewed in Turner and Alexander, 2006; Palmer et al, 2009).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"P52333-1",
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9701485",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9701485"
}
]
},
{
"id": "R-HSA-9701488",
"name": "Active ALK phosphorylates JAK3",
"equation": "",
"summary": "JAK3 is phosphorylated downstream of active ALK signaling (Zamo et al, 2002; Amin et al, 2003; Lai et al, 2005; Han et al, 2006a, b) Signaling through JAK3 and STAT3 contributes to cellular survival downstream of ALK signaling (Lai et al, 2005; Shi et al, 2006; reviewed in Palmer et al, 2009).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"P52333-1",
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9701488",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9701488"
}
]
},
{
"id": "R-HSA-9701507",
"name": "PTPN6 dephosphorylates JAK3",
"equation": "",
"summary": "PTPN6, also known as SHP1, dephosphorylates JAK3 downstream of ALK signaling, leading to the inactivation and increased proteolytic degradation of JAK3 (Han et al, 2006 a, b; reviewed in Palmer et al, 2009; Chiarle et al, 2008). PTPN6 gene expression is lost in some cases of anaplastic large cell lymphoma (ALCL) due to changes in promoter methylation, resulting in increased JAK3 activity in these cancers (Khoury et al, 2004; reviewed in Chiarle et al, 2008; Palmer et al, 2009).",
"cellular_location": "cytosol",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"P52333-1",
"Q9UM73-1",
"P29350-1"
],
"evidence": [
{
"id": "R-HSA-9701507",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9701507"
}
]
},
{
"id": "R-HSA-9701524",
"name": "STAT3 is phosphorylated downstream of active ALK",
"equation": "",
"summary": "STAT3 is phosphorylated at tyrosine 705 downstream of active ALK and oncogenic ALK fusion proteins and contributes to cellular survival (Zamo et al, 2002; Zhang et al, 2002; Amin et al, 2003; Chiarle et al, 2003; Chiarle et al, 2005; Sattu et al, 2013; reviewed in Turner and Alexander, 2006; Chiarle et al, 2008; Palmer et al, 2009). Whether STAT3 activation downstream of ALK is mediated directly by the receptor itself or depends on JAK3 is controversial (Zhang et al, 2002; Han et al 2006 a,b; Lai et al, 2005; Marzec et al. 2005; Shi et al, 2006; reviewed in Palmer et al, 2009). STAT3 is also phosphorylated at serine 727 in a manner that depends on the PI3K, mTOR and MAPK pathways. The functional significance of S727 phosphorylation is not entirely clear (Gambi et al, 2019). STAT3 supports cell survival by promoting the expression of a number of cell cycle and anti-apoptotic genes (reviewed in Chiarle et al, 2008).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [
"R-HSA-539048"
],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9701524",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9701524"
}
]
},
{
"id": "R-HSA-9712078",
"name": "ALK mutants bind PI3KR1",
"equation": "",
"summary": "Various ALK fusions and point mutants have been shown to form stable, active complexes with the PI3K and to activate downstream signaling through AKT/PKB (Bai et al, 2000; Slupianek et al, 2001; Slupianek and Tomasz, 2004; Marzec et al, 2007; Chen et al, 2008; Chand et al, 2013; George et al, 2008; Janoieux-Lerousey et al, 2008; Wong et al, 2011; Cerchietti et al, 2011; Wiesner et al, 2014; Koivunen et al, 2008; Ren et al, 2012; Cazes et al, 2013; Okubo et al, 2103; reviewed in Della Corte et al, 2018; Hallberg and Palmer, 2013; Ducray et al, 2019). Attempts to define a binding site for the p85 regulatory subunit of PI3K on NPM-ALK identified fragment with a putative p85 phospho-tyrosine binding site that was capable of blocking the interaction of PIK3R1 when co-expressed. In spite of this, mutation of the putative tyrosine residue did not block PIK3R1 binding, suggesting that the interaction may be mediated by an adaptor protein. SHC, CRKL and GAB2 each formed complexes with both PIK3R1 and NPM-ALK as assessed by co-immunoprecipitation, making them candidates (Bai et al, 2000).
Signaling through the PI3K/AKT pathway activates the anti-apoptotic pathway contributing to oncogenesis (Bai et al, 2000; Slupianek et al, 2001; reviewed in Rososki, 2013; Ducray et al, 2019).",
"cellular_location": "cytosol",
"input_participant_list": [
"R-HSA-9711929"
],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9712078",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9712078"
}
]
},
{
"id": "R-HSA-9712079",
"name": "ALK mutants bind STAT3",
"equation": "",
"summary": "The STAT3 signaling pathway is a major downstream target of several oncogenic ALK proteins (Zamo et al, 2002; Zhang et al, 2002; Amin et al, 2003; Chiarle et al, 2003; Chiarle et al, 2005; Koivunen et al, 2008; Takezawa et al, 2011; Cerchietti et al, 2011; Wong et al, 2011; Okubo et al, 2012; Cazes et al, 2013; reviewed in Chiarle et al, 2008; Hallberg and Palmer 2013; Hallberg and Palmer, 2016). STAT3 is phosphorylated at tyrosine 705 downstream of active ALK and oncogenic ALK fusion proteins and contributes to cellular survival (Zamo et al, 2002; Zhang et al, 2002; Amin et al, 2003; Chiarle et al, 2003; Chiarle et al, 2005; reviewed in Chiarle et al, 2008; Palmer et al, 2009). ; Whether STAT3 activation downstream of ALK is mediated directly by the receptor itself or depends on JAK3 is controversial (Zhang et al, 2002; Han et al 2006 a,b; Lai et al, 2005; Marzec et al. 2005; Shi et al, 2006; reviewed in Palmer et al, 2009). STAT3 is also phosphorylated at serine 727 in a manner that depends on the PI3K, mTOR and MAPK pathways. The functional significance of S727 phsophorylation is not entirely clear (Gambi et al, 2019). STAT3 supports cell survival by promoting the expression of a number of cell cycle and anti-apoptotic genes (reviewed in Chiarle et al, 2008).",
"cellular_location": "cytosol",
"input_participant_list": [
"R-HSA-9711944"
],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9712079",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9712079"
}
]
},
{
"id": "R-HSA-9712083",
"name": "ALK mutants bind PI3KCA",
"equation": "",
"summary": "The catalytic subunit of PI3K is recruited downstream ALK fusions and point mutants signal through the PI3K pathway as assessed by both binding and activity assays (Bai et al, 2000; Slupianek and Tomasz, 2001; Slupianek et al, 2004; Koivunen et al, 2008; George et al, 2008; Wang et al, 2011; reviewed in Roskoski, 2013; Hallberg and Palmer, 2013; Della Corte et al, 2018; Ducray et al, 2019).",
"cellular_location": "cytosol",
"input_participant_list": [
"R-HSA-9711928"
],
"output_participant_list": [
"R-HSA-9711926"
],
"enzyme_list": [
"P42336-1",
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9712083",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9712083"
}
]
},
{
"id": "R-HSA-9712084",
"name": "PI3K synthesizes PIP3 downstream of ALK mutants",
"equation": "",
"summary": "PI3K phosphorylates PIP2 to PIP3 downstream of activated ALK fusions and mutants, leading to activation of the AKT pathway as assessed by S473 phosphorylation (Bai et al, 2000; Slupianek et al, 2001; Slupianek et al, 2004; Chen et al, 2008). AKT signaling contributes to apoptotic escape and cellular proliferation through regulation of proteins such as CDKN1B/p27, CCND2 and BCL2L11/BIM, among others (Gu et al, 2004; Rassidakis et al, 2005; Marzec et al, 2007; reviewed in Chiarle et al, 2008; Hallberg and Palmer, 2013).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"P42336-1",
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9712084",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9712084"
}
]
},
{
"id": "R-HSA-9712085",
"name": "ALK mutants phosphorylate STAT3",
"equation": "",
"summary": "STAT3 is tyrosine phosphorylated at residue 705, and this phosphorylation is required for STAT3 dimerization, nuclear translocation, and DNA binding. The function of serine 727 phosphorylation is not clear, however it occurs independently of tyrosine phosphorylation (reviewed in Yu et al, 2014; Guanizo et al, 2018).",
"cellular_location": "cytosol",
"input_participant_list": [
"R-HSA-9711935"
],
"output_participant_list": [
"R-HSA-9712038"
],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9712085",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9712085"
}
]
},
{
"id": "R-HSA-9715355",
"name": "lorlatinib-resistant ALK mutants don't bind lorlatinib",
"equation": "",
"summary": "The following ALK mutants are resistant to inhibition by lorlatinib:
ALK I1171N: Ouseph et al, 2019
ALK I1171S: Takahashi et al, 2020
ALK L1196M: Yoda et al, 2018
ALK L1198F: Yoda et al, 2018
ALK G1202R: Kougioumtzi et al, 2019
ALK G1269A: Kougioumtzi et al, 2019; Takahashi et al, 2020; Yoda et al, 2018
",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9715355",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9715355"
}
]
},
{
"id": "R-HSA-9715356",
"name": "brigatinib-resistant ALK mutants don't bind brigatinib",
"equation": "",
"summary": "The following ALK mutants show resistance to brigatinib:
ALK L1122V: Ceccon et al, 2015
ALK I1171N: Ceccon et al, 2013
ALK 1171S: Amin et al, 2016
ALK I1171T: Katayama et al, 2021 (moderate)
ALK L1196M: Sharma et al, 2019; Ceccon et al, 2015 (moderate)
ALK L1198F: Ceccon et al, 2015
ALK G1202R: Sharma et al, 2019; Gainor et al, 2016
ALK D1203N: Gainor et al, 2016
ALK S1206C: Ceccon et al, 2015
",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9715356",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9715356"
}
]
},
{
"id": "R-HSA-9715357",
"name": "crizotinib-resistant ALK mutants don't bind crizotinib",
"equation": "",
"summary": "The following ALK mutants show resistance to inhibition by crizotinib:
ALK L1122V: Ceccon et al, 2015 (moderate)
ALK T1151dup: Katayama et al, 2012
ALK T1151M: Noe et al, 2020
ALK L1152R: Sasaki et al, 2011
ALK C1156Y: Noe et al, 2020; Saber et al 2016; Huang et al, 2013; Choi et al, 2010; Gainor et al, 2016
ALK I1171N: Gainor et al, 2016; Zhang et al, 2011; Ceccon et al, 2013
ALK I1171S: Gainor et al, 2016; Zhang et al, 2011
ALK I1171T: Noe et al, 2020; Toyokawa et al, 2014; Gainor et al, 2016; Zhang et al, 2011; Zdzalik et al, 2014; Katayama et al, 2014
ALK F1174C: Noe et al, 2020; Friboulet et al, 2014
ALK F1174L: Noe et al, 2020; Sasaki et al, 2010; Heuckmann et al, 2011
ALK F1174V: Noe et al, 2020; Ou et al, 2014
ALK V1180L: Katayama et al, 2014
ALK L1196M: Gainor et al, 2016; Huang et al, 2013; Katayama et al, 2012; Kim et al, 2013; Choi et al, 2010; Doebele et al, 2012; Friboulet et al, 2014; Heuckmann et al, 2011; Huang et al, 2013
ALK L1196Q: Ceccon et al, 2013
ALK L1198P: Heuckmann et al, 2011
ALK G1202R: Katayama et al, 2012; Noe et al, 2020; Kougiomtzi et al, 2019; Gainor et al, 2016, Ou et al, 2016; Chuang et al, 2019
ALK D1203N: Heuckmann et al, 2011
ALK S1206C: Ceccon et al, 2015
ALK S1206F: Noe et al, 2020
ALK S1206Y: Gainor et al, 2016; Friboulet et al, 2014; Katayama et al, 2012; Noe et al, 2020
ALK G1228A: Ai et al, 2018
ALK G1269A: Noe et al, 2020; Saber et al, 2016; Gainor et al, 2016; Friboulet et al, 2014; Huang et al, 2013; Kim et al, 2013; Xu et al, 2019; Doebele et al, 2012; Heuckmann et al, 2011; Amin et al, 2016
ALK G1269S: Heuckmann et al, 2011
",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9715357",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9715357"
}
]
},
{
"id": "R-HSA-9724099",
"name": "ALK mutants:p-3Y SHC binds GRB2",
"equation": "",
"summary": "GRB2 is found in complex with SHC in cells expressing a number of ALK fusion proteins and may contribute to signaling through the MAP kinase and PI3K pathways. In some backgrounds, GRB2 may also bind directly to the fusion protein itself to promote signaling (Fukimoto et al, 1996; Hernandez et al, 2002; Trinei et al, 2000; reviewed in Hallberg and Palmer, 2013; Hallberg and Palmer, 2016; Roskoski, 2013).",
"cellular_location": "cytosol",
"input_participant_list": [
"R-HSA-9699971"
],
"output_participant_list": [
"R-HSA-9724097"
],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9724099",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9724099"
}
]
},
{
"id": "R-HSA-9725117",
"name": "ALK gene expression",
"equation": "",
"summary": "18-38% percent of neuroblastomas show amplification of the MYCN gene, while the majority of familial and 10% of sporadic neuroblastomas carry activating mutations in the ALK kinase domain (Mosse et al, 2008; reviewed in Aygun, 2018; Roskoski, 2013). Amplifications of the ALK gene have also been reported in this disease (Caren et al, 2008). ALK and MYCN may play cooperative roles in driving progression of neuroblastoma (Zhu et al, 2012; Mosse et al, 2008; reviewed in Roskoski, 2013).
High levels of ALK expression are seen in MYCN amplified neuroblastomas, and inhibition of ALK activity with tyrosine kinase inhibitors in a MYCN-amplified background reduces proliferation, cell migration and tumor growth in xenograft models, suggesting that ALK activity contributes to the oncogenic potential of MYCN-driven neuroblastomas (Hasan et al, 2013; reviewed in Hallberg and Palmer, 2013).",
"cellular_location": "nucleoplasm, plasma membrane",
"input_participant_list": [
"R-HSA-9725096"
],
"output_participant_list": [
"R-HSA-201502"
],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9725117",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9725117"
}
]
},
{
"id": "R-HSA-9725315",
"name": "ALK-stimulated MYCN gene expression",
"equation": "",
"summary": "MYCN gene expression is stimulated downstream of wild-type and activated ALK signaling in neuronal and neuroblastoma cell lines as well as in murine neuroblastoma models (Schonherr et al, 2012; Montavon et al, 2014). MYCN and ALK are both located on chromosome 2, which is subject to amplifications in neuroblastoma, and ALK and MYCN are both implicated as contributing to neuroblastoma progression (Mosse et al, 2008; Caren et al, 2008; Hasan et al, 2012; De Brouwer et al, 2010; Montavon et al, 2012; Zhu et al, 2012). Abrogation of ALK activity with protein tyrosine kinase inhibitors or with anti-siRNA against ALK decreases MYCN transcript and protein levels, but the direct mechanisms for ALK-dependent MYCN gene expression have not been identified (Schonherr et al, 2012; Hallberg and Palmer, 2013; Roskoski, 2013).",
"cellular_location": "nucleoplasm",
"input_participant_list": [
"R-HSA-9725313"
],
"output_participant_list": [
"R-HSA-452357"
],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9725315",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9725315"
}
]
},
{
"id": "R-HSA-9842656",
"name": "ALK binds ALKAL ligand",
"equation": "",
"summary": "Signaling through the ALK receptor is activated by the binding of ALKAL ligand to the receptor extracellular region (Zhang et al, 2014; Guan et al, 2015; Reshetnyak et al, 2015; Reshetnyak et al, 2018; Reshetnyak et al, 2021; De Munck et al, 2021).
There are two human ALKAL proteins, ALKAL1 (also known as FAM150A) and ALKAL2 (also known as FAM150B). ALKAL1 and 2 were initially characterized as ligands for the ALK-related receptor leukocyte tyrosine kinase (LTK), and subsequently shown to bind to ALK as well (Zhang et al, 2014; Guan et al, 2015). Further studies revealed differences in ligand affinity for the two receptors, however, likely mediated by the differences in the extracellular domains of the two receptors. Although LTK is potently activated by both ALKAL1 and 2, robust activation of ALK in physiological contexts is only seen with ALKAL2 (Guan et al, 2015; Reshetnyak et al, 2015).
There is conflicting evidence as to whether ALKAL2 binds ALK as a monomer ((De Munck et al, 2021) or a dimer (Reshetnyak et al, 2018; Reshetnyak et al 2021). In this pathway, ALKAL2 is depicted as binding ALK as a dimer linked by interchain disulphide bond at residue C66 (Reshetnyak et al, 2018; Reshetnyak et al, 2021). Binding of ALKAL2 to the ALK receptor is also facilitated by binding of heparin to ALK (De Munck et al, 2021).",
"cellular_location": "extracellular region, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9842656",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9842656"
}
]
},
{
"id": "R-HSA-9850958",
"name": "pY-STAT3 dimer translocates to the nucleus downstream of ALK mutants",
"equation": "",
"summary": "STAT3 is a key regulator of transcriptional events downstream of oncogenic forms of ALK, including NPM-ALK (reviewed in Turner and Alexander, 2006; Chiarle et al, 2008; Ducray et al, 2019).
STAT3 is phosphorylated at tyrosine 705 downstream of active ALK and oncogenic ALK fusion proteins and contributes to cellular survival. Tyrosine phosphorylation at residue 705 is required for STAT3 dimerization, nuclear translocation, and DNA binding (Zamo et al, 2002; Zhang et al, 2002; Amin et al, 2003; Chiarle et al, 2003; Chiarle et al, 2005; reviewed in Chiarle et al, 2008; Palmer et al, 2009).
STAT3 is also phosphorylated at serine 727 in a manner that depends on the PI3K, mTOR and MAPK pathways. The functional significance of S727 phosphorylation is not entirely clear (Gambi et al, 2019).
Whether STAT3 activation downstream of ALK is mediated directly by the receptor itself or depends on JAK3 is controversial (Zhang et al, 2002; Han et al 2006 a,b; Lai et al, 2005; Marzec et al. 2005; Shi et al, 2006; reviewed in Palmer et al, 2009). STAT3 supports cell survival by promoting the expression of a number of cell cycle and anti-apoptotic genes (reviewed in Chiarle et al, 2008; Ducray et al, 2019).",
"cellular_location": "cytosol, nucleoplasm",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-HSA-9850958",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9850958"
}
]
},
{
"id": "R-NUL-9700161",
"name": "p-7Y ALK dimer phosphorylates Frs2",
"equation": "",
"summary": "Frs2 is phosphorylated in an ALK kinase-dependent manner when Frs2 and ALK are co-expressed in HEK293 cells (Degoutin et al, 2007).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-NUL-9700161",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-NUL-9700161"
}
]
},
{
"id": "R-NUL-9700655",
"name": "Active ALK phosphorylates Src",
"equation": "",
"summary": "Endogenous Src is phosphorylated when co-expressed in Ba/F3 cells with the human NPM-ALK fusion in a manner that depends on ALK kinase activity (Cussac et al, 2004).",
"cellular_location": "plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-NUL-9700655",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-NUL-9700655"
}
]
},
{
"id": "R-NUL-9700661",
"name": "Active ALK binds Src",
"equation": "",
"summary": "The human NPM:ALK fusion interacts with SRC in a ALK-kinase dependent fashion when expressed in Ba/F3 cells (Cussac et al, 2004).",
"cellular_location": "cytosol, plasma membrane",
"input_participant_list": [],
"output_participant_list": [],
"enzyme_list": [
"Q9UM73-1"
],
"evidence": [
{
"id": "R-NUL-9700661",
"database": "Reactome",
"url": "https://www.reactome.org/PathwayBrowser/#R-NUL-9700661"
}
]
}
],
"reaction_participants": [
{
"participant_id": "R-ALL-9699973",
"participant_name": "type I ALK-binding TKIs [cytosol]",
"crossref": [
{
"id": "0004992",
"database": "Mondo",
"url": ""
}
]
},
{
"participant_id": "R-HSA-201502",
"participant_name": "ALK [plasma membrane]",
"crossref": [
{
"id": "2YT2",
"database": "PDB",
"url": ""
},
{
"id": "4CNH",
"database": "PDB",
"url": ""
},
{
"id": "ALK_HUMAN",
"database": "ZINC - Predictions - Purchasable",
"url": ""
},
{
"id": "4TT7",
"database": "PDB",
"url": ""
},
{
"id": "4CMT",
"database": "PDB",
"url": ""
},
{
"id": "7JYR",
"database": "PDB",
"url": ""
},
{
"id": "ENSG00000171094",
"database": "OpenTargets",
"url": ""
},
{
"id": "9G5I",
"database": "PDB",
"url": ""
},
{
"id": "7JYT",
"database": "PDB",
"url": ""
},
{
"id": "5FTO",
"database": "PDB",
"url": ""
},
{
"id": "4CLJ",
"database": "PDB",
"url": ""
},
{
"id": "7R7K",
"database": "PDB",
"url": ""
},
{
"id": "ALK",
"database": "GeneCards",
"url": ""
},
{
"id": "6E0R",
"database": "PDB",
"url": ""
},
{
"id": "2YS5",
"database": "PDB",
"url": ""
},
{
"id": "2YFX",
"database": "PDB",
"url": ""
},
{
"id": "ALK_HUMAN",
"database": "ZINC - Biogenic",
"url": ""
},
{
"id": "4FNY",
"database": "PDB",
"url": ""
},
{
"id": "7N00",
"database": "PDB",
"url": ""
},
{
"id": "ENSG00000171094",
"database": "ENSEMBL",
"url": ""
},
{
"id": "7JYS",
"database": "PDB",
"url": ""
},
{
"id": "5IUG",
"database": "PDB",
"url": ""
},
{
"id": "4Z55",
"database": "PDB",
"url": ""
},
{
"id": "9GBE",
"database": "PDB",
"url": ""
},
{
"id": "7BTT",
"database": "PDB",
"url": ""
},
{
"id": "ENST00000389048",
"database": "ENSEMBL",
"url": ""
},
{
"id": "4CCU",
"database": "PDB",
"url": ""
},
{
"id": "4CLI",
"database": "PDB",
"url": ""
},
{
"id": "HMDBP01223",
"database": "HMDB Protein",
"url": ""
},
{
"id": "6EBW",
"database": "PDB",
"url": ""
},
{
"id": "5AAB",
"database": "PDB",
"url": ""
},
{
"id": "3L9P",
"database": "PDB",
"url": ""
},
{
"id": "ALK_HUMAN",
"database": "ZINC - Investigational",
"url": ""
},
{
"id": "2YJS",
"database": "PDB",
"url": ""
},
{
"id": "6CDT",
"database": "PDB",
"url": ""
},
{
"id": "3LCS",
"database": "PDB",
"url": ""
},
{
"id": "4FOD",
"database": "PDB",
"url": ""
},
{
"id": "4FNX",
"database": "PDB",
"url": ""
},
{
"id": "Q9UM73",
"database": "ZINC target",
"url": ""
},
{
"id": "7R7R",
"database": "PDB",
"url": ""
},
{
"id": "5KZ0",
"database": "PDB",
"url": ""
},
{
"id": "4MKC",
"database": "PDB",
"url": ""
},
{
"id": "4JOA",
"database": "PDB",
"url": ""
},
{
"id": "7NX4",
"database": "PDB",
"url": ""
},
{
"id": "7MZY",
"database": "PDB",
"url": ""
},
{
"id": "5A9U",
"database": "PDB",
"url": ""
},
{
"id": "2XB7",
"database": "PDB",
"url": ""
},
{
"id": "Q9UM73",
"database": "Pharos - Targets",
"url": ""
},
{
"id": "8ARJ",
"database": "PDB",
"url": ""
},
{
"id": "5IMX",
"database": "PDB",
"url": ""
},
{
"id": "Q9UM73",
"database": "UniProt",
"url": ""
},
{
"id": "4CTB",
"database": "PDB",
"url": ""
},
{
"id": "4CMO",
"database": "PDB",
"url": ""
},
{
"id": "Q9UM73",
"database": "GlyGen",
"url": ""
},
{
"id": "4FOC",
"database": "PDB",
"url": ""
},
{
"id": "2XBA",
"database": "PDB",
"url": ""
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{
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{
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}
]
}
]
},
{
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{
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}
]
},
{
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}
]
}
]
},
{
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{
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}
]
},
{
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{
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}
]
}
]
},
{
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{
"ec_number": "3.1.3.48",
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{
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}
]
},
{
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{
"id": "P23471",
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}
]
}
]
},
{
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{
"ec_number": "2.7.10.1",
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{
"id": "P29317",
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"url": "https://www.uniprot.org/uniprotkb/P29317"
}
]
},
{
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"activity": "",
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{
"id": "P29317",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P29317"
}
]
}
]
},
{
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{
"ec_number": "2.7.10.1",
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"url": "https://www.uniprot.org/uniprotkb/P29320"
}
]
},
{
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"activity": "",
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{
"id": "P29320",
"database": "UniProtKB",
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}
]
}
]
},
{
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{
"ec_number": "2.7.10.1",
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{
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}
]
},
{
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{
"id": "P29322",
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}
]
}
]
},
{
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{
"ec_number": "2.7.10.1",
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{
"id": "P29323",
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}
]
},
{
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{
"id": "P29323",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P29323"
}
]
}
]
},
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{
"ec_number": "3.1.3.48",
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"id": "P29350",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P29350"
}
]
},
{
"ec_number": "3.1.3.48",
"activity": "",
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{
"id": "P29350",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P29350"
}
]
}
]
},
{
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{
"ec_number": "2.7.10.1",
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{
"id": "P29376",
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}
]
},
{
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{
"id": "P29376",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P29376"
}
]
}
]
},
{
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"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
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"id": "P29597",
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"url": "https://www.uniprot.org/uniprotkb/P29597"
}
]
},
{
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"activity": "",
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{
"id": "P29597",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P29597"
}
]
}
]
},
{
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"ec_number": "2.7.10.2",
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{
"id": "P30291",
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}
]
},
{
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{
"id": "P30291",
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}
]
}
]
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{
"ec_number": "2.7.10.1",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
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{
"id": "P30530",
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"url": "https://www.uniprot.org/uniprotkb/P30530"
}
]
},
{
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{
"id": "P30530",
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}
]
}
]
},
{
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{
"ec_number": "2.7.12.1",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
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{
"id": "P33981",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P33981"
}
]
},
{
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"activity": "",
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{
"id": "P33981",
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"url": "https://www.uniprot.org/uniprotkb/P33981"
}
]
}
]
},
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{
"ec_number": "2.7.10.1",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P35590",
"database": "UniProtKB",
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}
]
},
{
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"id": "P35590",
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}
]
}
]
},
{
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{
"ec_number": "2.7.1.32",
"activity": "choline + ATP = phosphocholine + ADP + H(+).",
"evidence": [
{
"id": "P35790",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P35790"
}
]
},
{
"ec_number": "2.7.1.82",
"activity": "ethanolamine + ATP = phosphoethanolamine + ADP + H(+).",
"evidence": [
{
"id": "P35790",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P35790"
}
]
},
{
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"activity": "",
"evidence": [
{
"id": "P35790",
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}
]
},
{
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"activity": "",
"evidence": [
{
"id": "P35790",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P35790"
}
]
}
]
},
{
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{
"ec_number": "2.7.10.1",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P35916",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P35916"
}
]
},
{
"ec_number": "2.7.10.1",
"activity": "",
"evidence": [
{
"id": "P35916",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P35916"
}
]
}
]
},
{
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"gene_name": "KDR",
"activity": [
{
"ec_number": "2.7.10.1",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P35968",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P35968"
}
]
},
{
"ec_number": "2.7.10.1",
"activity": "",
"evidence": [
{
"id": "P35968",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P35968"
}
]
}
]
},
{
"uniprot_ac": "P36507",
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"activity": [
{
"ec_number": "2.7.12.2",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
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{
"id": "P36507",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P36507"
}
]
},
{
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"activity": "",
"evidence": [
{
"id": "P36507",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P36507"
}
]
}
]
},
{
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"activity": [
{
"ec_number": "2.7.10.1",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P36888",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P36888"
}
]
},
{
"ec_number": "2.7.10.1",
"activity": "",
"evidence": [
{
"id": "P36888",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P36888"
}
]
}
]
},
{
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{
"ec_number": "2.7.10.4",
"activity": "ATP + [a protein]-(L-tyrosine) = ADP + [a protein]-(L-tyrosine)-phosphate. The optimal peptide substrate contains the sequence (relative to the phosphorylated tyrosine): Glu-Glu-Asp/Glu-Ile-Tyr-Phe-Phe-Phe-Phe. Physiological substrates are C-terminal tail of Src-family protein kinases.",
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{
"id": "P41240",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P41240"
}
]
},
{
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"activity": "",
"evidence": [
{
"id": "P41240",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P41240"
}
]
}
]
},
{
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{
"ec_number": "2.7.11.1",
"activity": "L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+).",
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{
"id": "P42336",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42336"
}
]
},
{
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"evidence": [
{
"id": "P42336",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42336"
}
]
},
{
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"evidence": [
{
"id": "P42336",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42336"
}
]
},
{
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"activity": "",
"evidence": [
{
"id": "P42336",
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}
]
},
{
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{
"id": "P42336",
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}
]
}
]
},
{
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{
"ec_number": "2.7.11.1",
"activity": "L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+).",
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{
"id": "P42338",
"database": "UniProtKB",
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}
]
},
{
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{
"id": "P42338",
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}
]
},
{
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{
"id": "P42338",
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"url": "https://www.uniprot.org/uniprotkb/P42338"
}
]
},
{
"ec_number": "2.7.1.137",
"activity": "a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+).",
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{
"id": "P42338",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42338"
}
]
},
{
"ec_number": "2.7.1.137",
"activity": "",
"evidence": [
{
"id": "P42338",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42338"
}
]
}
]
},
{
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{
"ec_number": "2.7.10.2",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P42345",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42345"
}
]
},
{
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"activity": "L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P42345",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42345"
}
]
},
{
"ec_number": "2.7.11.1",
"activity": "",
"evidence": [
{
"id": "P42345",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42345"
}
]
}
]
},
{
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{
"ec_number": "2.7.10.2",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P42679",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42679"
}
]
},
{
"ec_number": "2.7.10.2",
"activity": "",
"evidence": [
{
"id": "P42679",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42679"
}
]
}
]
},
{
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"activity": [
{
"ec_number": "2.7.10.2",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P42680",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42680"
}
]
},
{
"ec_number": "2.7.10.2",
"activity": "",
"evidence": [
{
"id": "P42680",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42680"
}
]
}
]
},
{
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"activity": [
{
"ec_number": "2.7.10.2",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P42681",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42681"
}
]
},
{
"ec_number": "2.7.10.2",
"activity": "",
"evidence": [
{
"id": "P42681",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42681"
}
]
}
]
},
{
"uniprot_ac": "P42684",
"gene_name": "ABL2",
"activity": [
{
"ec_number": "2.7.10.2",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P42684",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42684"
}
]
},
{
"ec_number": "2.7.10.2",
"activity": "",
"evidence": [
{
"id": "P42684",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42684"
}
]
}
]
},
{
"uniprot_ac": "P42685",
"gene_name": "FRK",
"activity": [
{
"ec_number": "2.7.10.2",
"activity": "L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+).",
"evidence": [
{
"id": "P42685",
"database": "UniProtKB",
"url": "https://www.uniprot.org/uniprotkb/P42685"
}
]
},
{
"ec_number": "2.7.10.2",
"activity": "",
"evidence": [
{
"id": "P42685",
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}
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}
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{
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{
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{
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{
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{
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}
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{
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}
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}
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{
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}
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