{ "uniprot_canonical_ac": "O14508-1", "uniprot_ac": "O14508", "uniprot_id": "SOCS2_HUMAN", "mass": { "chemical_mass": 22172.0, "monoisotopic_mass": 22172.0 }, "refseq": { "ac": "NP_001257396", "name": "suppressor of cytokine signaling 2", "summary": "This gene encodes a member of the suppressor of cytokine signaling (SOCS) family. SOCS family members are cytokine-inducible negative regulators of cytokine receptor signaling via the Janus kinase/signal transducer and activation of transcription pathway (the JAK/STAT pathway). SOCS family proteins interact with major molecules of signaling complexes to block further signal transduction, in part, by proteasomal depletion of receptors or signal-transducing proteins via ubiquitination. The expression of this gene can be induced by a subset of cytokines, including erythropoietin, GM-CSF, IL10, interferon (IFN)-gamma and by cytokine receptors such as growth horomone receptor. The protein encoded by this gene interacts with the cytoplasmic domain of insulin-like growth factor-1 receptor (IGF1R) and is thought to be involved in the regulation of IGF1R mediated cell signaling. This gene has pseudogenes on chromosomes 20 and 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012].", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396" }, "gene_names": [ { "name": "SOCS2", "resource": "UniProtKB", "type": "recommended", "url": "https://www.uniprot.org/uniprot/O14508", "id": "O14508" }, { "name": "CIS2; Cish2; SOCS-2; SSI-2; SSI2; STATI2", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396", "id": "NP_001257396" }, { "name": "CIS2", "resource": "UniProtKB", "type": "synonym", "url": "https://www.uniprot.org/uniprot/O14508", "id": "O14508" }, { "name": "SOCS2", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396", "id": "NP_001257396" }, { "name": "SSI2", "resource": "UniProtKB", "type": "synonym", "url": "https://www.uniprot.org/uniprot/O14508", "id": "O14508" }, { "name": "STATI2", "resource": "UniProtKB", "type": "synonym", "url": "https://www.uniprot.org/uniprot/O14508", "id": "O14508" } ], "protein_names": [ { "name": "Suppressor of cytokine signaling 2", "resource": "UniProtKB", "type": "recommended", "url": "", "id": "O14508" }, { "name": "CIS-2", "resource": "UniProtKB", "type": "synonym", "url": "", "id": "O14508" }, { "name": "Cytokine-inducible SH2 protein 2", "resource": "UniProtKB", "type": "synonym", "url": "", "id": "O14508" }, { "name": "SOCS-2", "resource": "UniProtKB", "type": "synonym", "url": "", "id": "O14508" }, { "name": "SSI-2", "resource": "UniProtKB", "type": "synonym", "url": "", "id": "O14508" }, { "name": "STAT-induced STAT inhibitor 2", "resource": "UniProtKB", "type": "synonym", "url": "", "id": "O14508" }, { "name": "cytokine-inducible SH2 protein 2; CIS-2; STAT-induced STAT inhibitor 2", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396", "id": "NP_001257396" }, { "name": "suppressor of cytokine signaling 2", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396", "id": "NP_001257396" } ], "function": [ { "annotation": "CTRP6 protects against ferroptosis to drive lung cancer progression and metastasis by destabilizing SOCS2 and augmenting the xCT/GPX4 pathway.", "evidence": [ { "database": "RefSeq", "id": "NP_001257396", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396" }, { "database": "PubMed", "id": "38084702", "url": "https://glygen.org/publication/PubMed/38084702" } ] }, { "annotation": "Circ_0008797 attenuates non-small cell lung cancer proliferation, metastasis, and aerobic glycolysis by sponging miR-301a-3p/SOCS2.", "evidence": [ { "database": "RefSeq", "id": "NP_001257396", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396" }, { "database": "PubMed", "id": "35305058", "url": "https://glygen.org/publication/PubMed/35305058" } ] }, { "annotation": "MiR-532-3p inhibited the methylation of SOCS2 to suppress the progression of PC by targeting DNMT3A. Publication Status: Online-Only", "evidence": [ { "database": "RefSeq", "id": "NP_001257396", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396" }, { "database": "PubMed", "id": "37085288", "url": "https://glygen.org/publication/PubMed/37085288" } ] }, { "annotation": "SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS2 appears to be a negative regulator in the growth hormone/IGF1 signaling pathway. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.", "evidence": [ { "database": "UniProtKB", "id": "O14508", "url": "https://www.uniprot.org/uniprot/O14508#function" } ] }, { "annotation": "SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway. Publication Status: Online-Only", "evidence": [ { "database": "RefSeq", "id": "NP_001257396", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396" }, { "database": "PubMed", "id": "38071211", "url": "https://glygen.org/publication/PubMed/38071211" } ] }, { "annotation": "This gene encodes a member of the suppressor of cytokine signaling (SOCS) family. SOCS family members are cytokine-inducible negative regulators of cytokine receptor signaling via the Janus kinase/signal transducer and activation of transcription pathway (the JAK/STAT pathway). SOCS family proteins interact with major molecules of signaling complexes to block further signal transduction, in part, by proteasomal depletion of receptors or signal-transducing proteins via ubiquitination. The expression of this gene can be induced by a subset of cytokines, including erythropoietin, GM-CSF, IL10, interferon (IFN)-gamma and by cytokine receptors such as growth horomone receptor. The protein encoded by this gene interacts with the cytoplasmic domain of insulin-like growth factor-1 receptor (IGF1R) and is thought to be involved in the regulation of IGF1R mediated cell signaling. This gene has pseudogenes on chromosomes 20 and 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2012].", "evidence": [ { "database": "RefSeq", "id": "NP_001257396", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396" } ] }, { "annotation": "Upregulation of SOCS2 causes mitochondrial dysfunction and promotes ferroptosis in pancreatic cancer cells.", "evidence": [ { "database": "RefSeq", "id": "NP_001257396", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001257396" }, { "database": "PubMed", "id": "36735705", "url": "https://glygen.org/publication/PubMed/36735705" } ] } ], "disease": [], "snv": [ { "evidence": [ { "id": "O14508", "database": "BioMuta", "url": "https://hive.biochemistry.gwu.edu/biomuta/proteinview/O14508" } ], "glycoeffect": [], "start_pos": 96, "end_pos": 96, "subjects_tested": "0", "subjects_positive": "0", "frequency": "0.0", "sequence_org": "R", "sequence_mut": "Q", "comment": "Somatic mutation passed 1 out of 6 filters: num. of cancers (3).", "chr_id": "12", "chr_pos": "93574869", "ref_nt": "G", "alt_nt": "A", "minor_allelic_frequency": "", "site_lbl": "R96", "disease": [ { "disease_id": "DOID:363", "recommended_name": { "id": "DOID:363", "resource": "Disease Ontology", "url": "http://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", "url": "http://disease-ontology.org/term/DOID:363", "name": "CA - cancer of uterus", "description": "" }, { "id": "DOID:363", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:363", "name": "Tumour of uterus", "description": "" }, { "id": "DOID:363", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:363", "name": "malignant neoplasm of uterus", "description": "" }, { "id": "DOID:363", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:363", "name": "malignant uterine tumor", "description": "" }, { "id": "DOID:363", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:363", "name": "neoplasm of uterus", "description": "" }, { "id": "DOID:363", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:363", "name": "uterine tumor", "description": "" }, { "id": "DOID:363", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:363", "name": "uterus neoplasm", "description": "" } ] }, { "disease_id": "DOID:9256", "recommended_name": { "id": "DOID:9256", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:9256", "name": "colorectal cancer", "description": "A large intestine cancer that is located_in the colon and/or located_in the rectum." }, "synonyms": [ { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "colorectal cancer", "description": "A primary or metastatic malignant neoplasm that affects the colon or rectum. 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"https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant neoplasm of colorectum", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant neoplasm of large bowel", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant neoplasm of large intestine", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant neoplasm of the large bowel", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant neoplasm of the large intestine", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant tumor of large bowel", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant tumor of large intestine", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant tumor of the large bowel", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant tumor of the large intestine", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant tumour of large bowel", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": "malignant tumour of large intestine", "description": "" }, { "id": "MONDO:0005575", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0005575", "name": 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neoplasm", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "brain neoplasm, adult", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "malignant brain tumour", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "malignant primary brain neoplasm", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "malignant primary brain tumor", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "malignant tumor of Brain", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "malignant tumor of adult brain", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "neoplasm of brain", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "primary brain neoplasm", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "primary brain tumor", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "primary malignant neoplasm of brain", "description": "" }, { "id": "DOID:1319", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1319", "name": "tumor of the Brain", "description": "" } ] } ], "keywords": [ "biomuta", "somatic", "cancer", "disease" ] } ], "mutagenesis": [ { "start_pos": 154, "end_pos": 154, "sequence_org": "K", "sequence_mut": "R", "comment": "No effect on protein half-life.", "evidence": [ { "database": "UniProtKB", "id": "O14508", "url": "https://www.uniprot.org/uniprot/O14508" }, { "database": "PubMed", "id": "31578312", "url": "https://glygen.org/publication/PubMed/31578312" } ] }, { "start_pos": 173, "end_pos": 173, "sequence_org": "K", "sequence_mut": "R", "comment": "Increased protein half-life.", "evidence": [ { "database": "UniProtKB", "id": "O14508", "url": "https://www.uniprot.org/uniprot/O14508" }, { "database": "PubMed", "id": "31578312", "url": "https://glygen.org/publication/PubMed/31578312" } ] }, { "start_pos": 87, "end_pos": 87, "sequence_org": "K", "sequence_mut": "R", "comment": "No effect on protein half-life.", "evidence": [ { "database": "UniProtKB", "id": "O14508", "url": "https://www.uniprot.org/uniprot/O14508" }, { "database": "PubMed", "id": "31578312", "url": "https://glygen.org/publication/PubMed/31578312" } ] } ], "expression_tissue": [ { "tissue": { "name": "Adult mammalian kidney", "namespace": "UBERON", "id": "0000082", "url": "http://purl.obolibrary.org/obo/UBERON_0000082" }, "score": "88.02", "present": "HIGH", "evidence": [ { "database": "Bgee", "id": "ENSG00000120833", "url": "https://bgee.org/?page=gene&gene_id=ENSG00000120833" } ] }, { "tissue": { "name": "Oral cavity", "namespace": "UBERON", "id": "0000167", "url": "http://purl.obolibrary.org/obo/UBERON_0000167" }, "score": "77.88", "present": "MEDIUM", "evidence": [ { "database": "Bgee", "id": "ENSG00000120833", "url": "https://bgee.org/?page=gene&gene_id=ENSG00000120833" } ] }, { "tissue": { "name": "Stomach", "namespace": "UBERON", "id": "0000945", "url": "http://purl.obolibrary.org/obo/UBERON_0000945" }, "score": "80.61", "present": "HIGH", "evidence": [ { "database": "Bgee", "id": "ENSG00000120833", "url": "https://bgee.org/?page=gene&gene_id=ENSG00000120833" } ] }, { "tissue": { "name": "Uterus", "namespace": "UBERON", "id": "0000995", "url": "http://purl.obolibrary.org/obo/UBERON_0000995" }, "score": "87.2", "present": "HIGH", "evidence": [ { "database": "Bgee", "id": "ENSG00000120833", "url": "https://bgee.org/?page=gene&gene_id=ENSG00000120833" } ] }, { "tissue": { "name": "Esophagus", "namespace": "UBERON", "id": "0001043", "url": "http://purl.obolibrary.org/obo/UBERON_0001043" }, "score": "90.49", "present": "HIGH", "evidence": [ { "database": "Bgee", "id": "ENSG00000120833", "url": "https://bgee.org/?page=gene&gene_id=ENSG00000120833" } ] }, { "tissue": { "name": "Rectum", "namespace": "UBERON", "id": "0001052", "url": "http://purl.obolibrary.org/obo/UBERON_0001052" }, "score": "87.7", "present": "HIGH", "evidence": [ { "database": "Bgee", "id": "ENSG00000120833", "url": "https://bgee.org/?page=gene&gene_id=ENSG00000120833" } ] }, { "tissue": { "name": "Colon", "namespace": "UBERON", "id": "0001155", "url": "http://purl.obolibrary.org/obo/UBERON_0001155" }, "score": "76.3", "present": "MEDIUM", "evidence": [ { "database": "Bgee", "id": "ENSG00000120833", "url": "https://bgee.org/?page=gene&gene_id=ENSG00000120833" } ] }, { "tissue": { "name": "Urinary bladder", "namespace": "UBERON", "id": "0001255", "url": "http://purl.obolibrary.org/obo/UBERON_0001255" }, "score": "93.23", "present": "HIGH", "evidence": [ { "database": "Bgee", "id": "ENSG00000120833", "url": "https://bgee.org/?page=gene&gene_id=ENSG00000120833" } ] }, { "tissue": { "name": "Thyroid gland", "namespace": "UBERON", "id": "0002046", "url": "http://purl.obolibrary.org/obo/UBERON_0002046" }, "score": "91.49", "present": "HIGH", "evidence": [ { "database": "Bgee", "id": "ENSG00000120833", "url": "https://bgee.org/?page=gene&gene_id=ENSG00000120833" } ] }, { "tissue": { "name": "Lung", "namespace": "UBERON", "id": "0002048", "url": "http://purl.obolibrary.org/obo/UBERON_0002048" }, "score": "95.23", "present": "HIGH", "evidence": [ { "database": "Bgee", "id": "ENSG00000120833", "url": "https://bgee.org/?page=gene&gene_id=ENSG00000120833" } ] }, { "tissue": { "name": "Liver", 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"http://disease-ontology.org/term/DOID:10283", "evidence": [ { "database": "BioXpress", "id": "O14508", "url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O14508" } ], "disease": [ { "disease_id": "DOID:10283", "recommended_name": { "id": "DOID:10283", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:10283", "name": "prostate cancer", "description": "A male reproductive organ cancer that is located_in the prostate." }, "synonyms": [ { "id": "DOID:10283", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:10283", "name": "NGP - new growth of prostate", "description": "" }, { "id": "DOID:10283", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:10283", "name": "hereditary prostate cancer", "description": "" }, { "id": "DOID:10283", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:10283", "name": "malignant tumor of the prostate", "description": "" }, { "id": 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"" }, { "id": "MONDO:0012094", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0012094", "name": "prostate cancer, hereditary, on chromosome 7", "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": 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"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": "prostate cancer aggressiveness", "description": "" }, { "id": "MONDO:0011098", "resource": "MONDO", "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": 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Male", "description": "" }, { "id": "MIM:114480", "resource": "MIM", "url": "https://www.omim.org/entry/114480", "name": "Breast cancer", "description": "Breast cancer" } ] } ] }, { "significant": "Yes", "trend": "down", "name": "Thyroid cancer [DO disease name]", "url": "http://disease-ontology.org/term/DOID:1781", "evidence": [ { "database": "BioXpress", "id": "O14508", "url": "https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O14508" } ], "disease": [ { "disease_id": "DOID:1781", "recommended_name": { "id": "DOID:1781", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1781", "name": "thyroid cancer", "description": "An endocrine gland cancer located in the thryoid gland located in the neck below the thyroid cartilage." }, "synonyms": [ { "id": "DOID:1781", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:1781", "name": "thyroid gland cancer", "description": "" }, { "id": "DOID:1781", "resource": "Disease Ontology", 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"https://hive.biochemistry.gwu.edu/bioxpress/transcriptview/O14508" } ], "disease": [ { "disease_id": "DOID:263", "recommended_name": { "id": "DOID:263", "resource": "Disease Ontology", "url": "http://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": "http://disease-ontology.org/term/DOID:263", "name": "malignant neoplasm of kidney except pelvis", "description": "" }, { "id": "DOID:263", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:263", "name": "malignant tumour of kidney", "description": "" }, { "id": "DOID:263", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:263", "name": "renal cancer", "description": "" } ] } ] }, { "significant": "Yes", "trend": "down", "name": "Liver cancer [DO disease name]", "url": "http://disease-ontology.org/term/DOID:3571", "evidence": [ 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cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively.", "journal": "Genomics", "date": "1999", "authors": "Yandava C N, Pillari A, Drazen J M", "evidence": [ { "database": "UniProtKB", "id": "O14508", "url": "https://www.uniprot.org/uniprot/O14508" } ], "reference": [ { "type": "PubMed", "id": "10512686", "url": "https://glygen.org/publication/PubMed/10512686" } ] }, { "title": "Identification of the von Hippel-lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "date": "1999", "authors": "Iwai K, Yamanaka K, Kamura T, Minato N, Conaway RC, Conaway JW, Klausner RD, Pause A", "evidence": [ { "database": "Reactome", "id": "R-HSA-8951664", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-8951664" } ], "reference": [ { "type": "PubMed", "id": "10535940", "url": "https://glygen.org/publication/PubMed/10535940" } ] }, { "title": "Covalent modification of all members of human cullin family proteins by NEDD8.", "journal": "Oncogene", "date": "1999", "authors": "Hori T, Osaka F, Chiba T, Miyamoto C, Okabayashi K, Shimbara N, Kato S, Tanaka K", "evidence": [ { "database": "Reactome", "id": "R-HSA-8951664", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-8951664" } ], "reference": [ { "type": "PubMed", "id": "10597293", "url": "https://glygen.org/publication/PubMed/10597293" } ] }, { "title": "A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways.", "journal": "The EMBO journal", "date": "2000", "authors": "Meyer HH, Shorter JG, Seemann J, Pappin D, Warren G", "evidence": [ { "database": "Reactome", "id": "R-HSA-8951664", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-8951664" } ], "reference": [ { "type": "PubMed", "id": "10811609", "url": "https://glygen.org/publication/PubMed/10811609" } ] }, { "title": "Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein.", "journal": "Nature cell biology", "date": "2000", "authors": "Ohh M, Park CW, Ivan M, Hoffman MA, Kim TY, Huang LE, Pavletich N, Chau V, Kaelin WG", "evidence": [ { "database": "Reactome", "id": "R-HSA-8951664", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-8951664" } ], "reference": [ { "type": "PubMed", "id": "10878807", "url": "https://glygen.org/publication/PubMed/10878807" } ] }, { "title": "Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex.", "journal": "Proceedings of the National Academy of Sciences of the United States of America", "date": "2000", "authors": "Kamura T, Sato S, Iwai K, Czyzyk-Krzeska M, Conaway RC, Conaway JW", "evidence": [ { "database": "Reactome", "id": "R-HSA-8951664", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-8951664" } ], "reference": [ { "type": "PubMed", "id": "10973499", "url": 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] }, { "title": "Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.", "journal": "Science (New York, N.Y.)", "date": "2001", "authors": "Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ", "evidence": [ { "database": "Reactome", "id": "R-HSA-8951664", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-8951664" } ], "reference": [ { "type": "PubMed", "id": "11292861", "url": "https://glygen.org/publication/PubMed/11292861" } ] }, { "title": "HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.", "journal": "Science (New York, N.Y.)", "date": "2001", "authors": "Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr", "evidence": [ { "database": "Reactome", "id": "R-HSA-8951664", "url": 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McGlade CJ", "evidence": [ { "database": "Reactome", "id": "R-HSA-9706369", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-9706369" } ], "reference": [ { "type": "PubMed", "id": "12024036", "url": "https://glygen.org/publication/PubMed/12024036" } ] }, { "title": "Oxygen-dependent ubiquitination and degradation of hypoxia-inducible factor requires nuclear-cytoplasmic trafficking of the von Hippel-Lindau tumor suppressor protein.", "journal": "Molecular and cellular biology", "date": "2002", "authors": "Groulx I, Lee S", "evidence": [ { "database": "Reactome", "id": "R-HSA-8951664", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-8951664" } ], "reference": [ { "type": "PubMed", "id": "12101228", "url": "https://glygen.org/publication/PubMed/12101228" } ] }, { "title": "Pre-pro-B cell growth-stimulating factor (PPBSF) upregulates IL-7Ralpha chain expression and enables pro-B cells to respond to monomeric IL-7.", "journal": "Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research", "date": "2002", "authors": "Wei C, Lai L, Goldschneider I", "evidence": [ { "database": "Reactome", "id": "R-HSA-1266695", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-1266695" } ], "reference": [ { "type": "PubMed", "id": "12184921", "url": "https://glygen.org/publication/PubMed/12184921" } ] }, { "title": "Analysis of the adenovirus E1B-55K-anchored proteome reveals its link to ubiquitination machinery.", "journal": "Journal of virology", "date": "2002", "authors": "Harada JN, Shevchenko A, Shevchenko A, Pallas DC, Berk AJ", "evidence": [ { "database": "Reactome", "id": "R-HSA-8951664", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-8951664" } ], "reference": [ { "type": "PubMed", "id": "12186903", "url": "https://glygen.org/publication/PubMed/12186903" } ] }, { "title": "NEDD8 modification of CUL1 dissociates p120(CAND1), an inhibitor of CUL1-SKP1 binding and SCF ligases.", 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motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15.", "journal": "Immunity", "date": "1995", "authors": "Lin JX, Migone TS, Tsang M, Friedmann M, Weatherbee JA, Zhou L, Yamauchi A, Bloom ET, Mietz J, John S, et al.", "evidence": [ { "database": "Reactome", "id": "R-HSA-1266695", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-1266695" } ], "reference": [ { "type": "PubMed", "id": "7719938", "url": "https://glygen.org/publication/PubMed/7719938" } ] }, { "title": "Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes.", "journal": "Science (New York, N.Y.)", "date": "1994", "authors": "Kondo M, Takeshita T, Higuchi M, Nakamura M, Sudo T, Nishikawa S, Sugamura K", "evidence": [ { "database": "Reactome", "id": "R-HSA-1266695", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-1266695" } ], "reference": [ { "type": "PubMed", "id": "8128231", "url": 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Chem.", "date": "1998", "authors": "Dey BR, Spence SL, Nissley P, Furlanetto RW", "evidence": [ { "database": "UniProtKB", "id": "O14508", "url": "https://www.uniprot.org/uniprot/O14508" } ], "reference": [ { "type": "PubMed", "id": "9727029", "url": "https://glygen.org/publication/PubMed/9727029" } ] }, { "title": "Cleavage of the C-terminus of NEDD8 by UCH-L3.", "journal": "Biochemical and biophysical research communications", "date": "1998", "authors": "Wada H, Kito K, Caskey LS, Yeh ET, Kamitani T", "evidence": [ { "database": "Reactome", "id": "R-HSA-8951664", "url": "https://www.reactome.org/PathwayBrowser/#R-HSA-8951664" } ], "reference": [ { "type": "PubMed", "id": "9790970", "url": "https://glygen.org/publication/PubMed/9790970" } ] }, { "title": "Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain.", "journal": "Genes & development", "date": "1999", "authors": "Itoh K, Wakabayashi N, Katoh Y, Ishii T, 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