{ "uniprot_canonical_ac": "A2AH22-1", "uniprot_ac": "A2AH22", "uniprot_id": "AMRA1_MOUSE", "mass": { "chemical_mass": 142879.0, "monoisotopic_mass": 142879.0 }, "refseq": { "ac": "NP_001074223", "name": "activating molecule in BECN1-regulated autophagy protein 1 isoform 2", "summary": "", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" }, "gene_names": [ { "name": "Ambra1", "resource": "UniProtKB", "type": "recommended", "url": "https://www.uniprot.org/uniprot/A2AH22", "id": "A2AH22" }, { "name": "2310079H06Rik; A130023A14; AA474864; AV021921; D030051N19Rik; mKIAA1736", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223", "id": "NP_001074223" }, { "name": "Ambra1", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223", "id": "NP_001074223" }, { "name": "Kiaa1736", "resource": "UniProtKB", "type": "synonym", "url": "https://www.uniprot.org/uniprot/A2AH22", "id": "A2AH22" } ], "protein_names": [ { "name": "Activating molecule in BECN1-regulated autophagy protein 1", "resource": "UniProtKB", "type": "recommended", "url": "https://www.uniprot.org/uniprot/A2AH22#names_and_taxonomy", "id": "A2AH22" }, { "name": "activating molecule in BECN1-regulated autophagy protein 1 isoform 2", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223", "id": "NP_001074223" }, { "name": "activating molecule in BECN1-regulated autophagy protein 1; activating molecule in Beclin1-regulated autophagy", "resource": "RefSeq", "type": "synonym", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223", "id": "NP_001074223" } ], "function": [ { "annotation": "AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity.", "evidence": [ { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" }, { "database": "PubMed", "id": "33854232", "url": "https://glygen.org/publication/PubMed/33854232" } ] }, { "annotation": "Ambra1 functional deficiency in mouse embryos leads to severe neural tube defects associated with autophagy impairment, accumulation of ubiquitinated proteins, unbalanced cell proliferation and excessive apoptotic cell death", "evidence": [ { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" }, { "database": "PubMed", "id": "17589504", "url": "https://glygen.org/publication/PubMed/17589504" } ] }, { "annotation": "CRL4(AMBRA1) is a master regulator of D-type cyclins.", "evidence": [ { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" }, { "database": "PubMed", "id": "33854235", "url": "https://glygen.org/publication/PubMed/33854235" } ] }, { "annotation": "Loss of Ambra1 promotes melanoma growth and invasion. Publication Status: Online-Only", "evidence": [ { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" }, { "database": "PubMed", "id": "33953176", "url": "https://glygen.org/publication/PubMed/33953176" } ] }, { "annotation": "Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy (PubMed:17589504, PubMed:33854232, PubMed:33854235, PubMed:33854239). The DCX(AMBRA1) complex specifically mediates the polyubiquitination of target proteins such as BECN1, CCND1, CCND2, CCND3, ELOC and ULK1 (PubMed:23974797, PubMed:33854232, PubMed:33854235, PubMed:33854239). Acts as an upstream master regulator of the transition from G1 to S cell phase: AMBRA1 specifically recognizes and binds phosphorylated cyclin-D (CCND1, CCND2 and CCND3), leading to cyclin-D ubiquitination by the DCX(AMBRA1) complex and subsequent degradation (PubMed:33854232, PubMed:33854235, PubMed:33854239). By controlling the transition from G1 to S phase and cyclin-D degradation, AMBRA1 acts as a tumor suppressor that promotes genomic integrity during DNA replication and counteracts developmental abnormalities and tumor growth (PubMed:33854232, PubMed:33854235, PubMed:33854239). AMBRA1 also regulates the cell cycle by promoting MYC dephosphorylation and degradation independently of the DCX(AMBRA1) complex: acts via interaction with the catalytic subunit of protein phosphatase 2A (PPP2CA), which enhances interaction between PPP2CA and MYC, leading to MYC dephosphorylation and degradation (PubMed:25438055). Acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (By similarity). Acts as a key regulator of autophagy by modulating the BECN1-PIK3C3 complex: controls protein turnover during neuronal development, and regulates normal cell survival and proliferation (PubMed:17589504). In normal conditions, AMBRA1 is tethered to the cytoskeleton via interaction with dyneins DYNLL1 and DYNLL2 (By similarity). Upon autophagy induction, AMBRA1 is released from the cytoskeletal docking site to induce autophagosome nucleation by mediating ubiquitination of proteins involved in autophagy (By similarity). The DCX(AMBRA1) complex mediates 'Lys-63'-linked ubiquitination of BECN1, increasing the association between BECN1 and PIK3C3 to promote PIK3C3 activity (PubMed:23974797). In collaboration with TRAF6, AMBRA1 mediates 'Lys-63'-linked ubiquitination of ULK1 following autophagy induction, promoting ULK1 stability and kinase activity (By similarity). Also activates ULK1 via interaction with TRIM32: TRIM32 stimulates ULK1 through unanchored 'Lys-63'-linked polyubiquitin chains (By similarity). Also acts as an activator of mitophagy via interaction with PRKN and LC3 proteins (MAP1LC3A, MAP1LC3B or MAP1LC3C); possibly by bringing damaged mitochondria onto autophagosomes (PubMed:21753002, PubMed:25215947). Also activates mitophagy by acting as a cofactor for HUWE1; acts by promoting HUWE1-mediated ubiquitination of MFN2 (By similarity). AMBRA1 is also involved in regulatory T-cells (Treg) differentiation by promoting FOXO3 dephosphorylation independently of the DCX(AMBRA1) complex: acts via interaction with PPP2CA, which enhances interaction between PPP2CA and FOXO3, leading to FOXO3 dephosphorylation and stabilization (PubMed:28789945, PubMed:30513302). May act as a regulator of intracellular trafficking, regulating the localization of active PTK2/FAK and SRC (PubMed:28362576). Also involved in transcription regulation by acting as a scaffold for protein complexes at chromatin (PubMed:32616651).", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22#function" }, { "database": "PubMed", "id": "17589504", "url": "https://glygen.org/publication/PubMed/17589504" }, { "database": "PubMed", "id": "Q9C0C7", "url": "https://glygen.org/publication/PubMed/Q9C0C7" }, { "database": "PubMed", "id": "23974797", "url": "https://glygen.org/publication/PubMed/23974797" }, { "database": "PubMed", "id": "25438055", "url": "https://glygen.org/publication/PubMed/25438055" }, { "database": "PubMed", "id": "28362576", "url": "https://glygen.org/publication/PubMed/28362576" }, { "database": "PubMed", "id": "21753002", "url": "https://glygen.org/publication/PubMed/21753002" }, { "database": "PubMed", "id": "33854235", "url": "https://glygen.org/publication/PubMed/33854235" }, { "database": "PubMed", "id": "32616651", "url": "https://glygen.org/publication/PubMed/32616651" }, { "database": "PubMed", "id": "25215947", "url": "https://glygen.org/publication/PubMed/25215947" }, { "database": "PubMed", "id": "33854239", "url": "https://glygen.org/publication/PubMed/33854239" }, { "database": "PubMed", "id": "33854232", "url": "https://glygen.org/publication/PubMed/33854232" }, { "database": "PubMed", "id": "30513302", "url": "https://glygen.org/publication/PubMed/30513302" }, { "database": "PubMed", "id": "28789945", "url": "https://glygen.org/publication/PubMed/28789945" } ] }, { "annotation": "The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D.", "evidence": [ { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" }, { "database": "PubMed", "id": "33854239", "url": "https://glygen.org/publication/PubMed/33854239" } ] }, { "annotation": "These data identify interaction of Parkin with Ambra1 as a key mechanism for induction of the final clearance step of Parkin-mediated mitophagy.", "evidence": [ { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" }, { "database": "PubMed", "id": "21753002", "url": "https://glygen.org/publication/PubMed/21753002" } ] } ], "disease": [ { "disease_id": "DOID:4752", "recommended_name": { "id": "DOID:4752", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:4752", "name": "multiple system atrophy", "description": "" }, "synonyms": [ { "id": "DOID:4752", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:4752", "name": "Multiple system atrophy", "description": "" }, { "id": "DOID:4752", "resource": "Disease Ontology", "url": "http://disease-ontology.org/term/DOID:4752", "name": "Shy-Drager syndrome", "description": "" }, { "id": "MONDO:0007803", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007803", "name": "multiple system atrophy", "description": "Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic failure (cardiovascular and/or urinary), parkinsonism, cerebellar impairment and corticospinal signs with a median survival of 6-9 years." }, { "id": "MONDO:0007803", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007803", "name": "Shy-dragger syndrome (formerly)", "description": "" }, { "id": "MONDO:0007803", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007803", "name": "susceptibility to multiple system atrophy 1", "description": "" }, { "id": "MONDO:0007803", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007803", "name": "Shy-Drager syndrome", "description": "" }, { "id": "MONDO:0007803", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007803", "name": "hypotension, orthostatic", "description": "" }, { "id": "MONDO:0007803", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007803", "name": "autonomic failure, Pure", "description": "" }, { "id": "MONDO:0007803", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007803", "name": "MSA", "description": "" }, { "id": "MONDO:0007803", "resource": "MONDO", "url": "https://monarchinitiative.org/disease/MONDO:0007803", "name": "multisystem atrophy", "description": "" }, { "id": "MIM:146500", "resource": "MIM", "url": "https://www.omim.org/entry/146500", "name": "Multiple system atrophy 1", "description": "Multiple system atrophy 1" } ], "evidence": [ { "id": "4752", "database": "Alliance of Genome Resources", "url": "https://www.alliancegenome.org/disease/DOID:4752" } ] } ], "snv": [], "mutagenesis": [ { "start_pos": 2, "end_pos": 2, "sequence_org": "K", "sequence_mut": "R", "comment": "Does not affect ubiquitination by RNF2.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "PubMed", "id": "24980959", "url": "https://glygen.org/publication/PubMed/24980959" } ] }, { "start_pos": 36, "end_pos": 36, "sequence_org": "K", "sequence_mut": "R", "comment": "Does not affect ubiquitination by RNF2.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "PubMed", "id": "24980959", "url": "https://glygen.org/publication/PubMed/24980959" } ] }, { "start_pos": 41, "end_pos": 41, "sequence_org": "K", "sequence_mut": "R", "comment": "Does not affect ubiquitination by RNF2.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "PubMed", "id": "24980959", "url": "https://glygen.org/publication/PubMed/24980959" } ] }, { "start_pos": 45, "end_pos": 45, "sequence_org": "K", "sequence_mut": "R", "comment": "Abolished ubiquitination by RNF2.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "PubMed", "id": "24980959", "url": "https://glygen.org/publication/PubMed/24980959" } ] }, { "start_pos": 7, "end_pos": 7, "sequence_org": "K", "sequence_mut": "R", "comment": "Does not affect ubiquitination by RNF2.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "PubMed", "id": "24980959", "url": "https://glygen.org/publication/PubMed/24980959" } ] } ], "expression_tissue": [], "expression_disease": [], "species": [ { "name": "Mus musculus", "taxid": 10090, "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "common_name": "Mouse" } ], "gene": [ { "name": "Ambra1", "url": "https://www.uniprot.org/uniprot/A2AH22", "locus": { "chromosome": "2", "start_pos": 91730134, "end_pos": 91918849, "strand": "+", "evidence": [ { "database": "Ensembl Gene", "id": "ENSMUSG00000040506", "url": "https://www.ensembl.org/id/ENSMUSG00000040506" } ] } } ], "crossref": [ { "id": "ENSMUSG00000040506", "url": "https://bgee.org/?page=gene&gene_id=ENSMUSG00000040506", "database": "Bgee" }, { "id": "228361", "url": "https://www.ncbi.nlm.nih.gov/gene/228361", "database": "GeneID" }, { "id": "A2AH22", "url": "https://www.ebi.ac.uk/intact/interactors/id:A2AH22*", "database": "IntAct" }, { "id": "IPR001680", "url": "https://www.ebi.ac.uk/interpro/entry/IPR001680", "database": "InterPro" }, { "id": "IPR015943", "url": "https://www.ebi.ac.uk/interpro/entry/IPR015943", "database": "InterPro" }, { "id": "IPR019775", "url": "https://www.ebi.ac.uk/interpro/entry/IPR019775", "database": "InterPro" }, { "id": "IPR036322", "url": "https://www.ebi.ac.uk/interpro/entry/IPR036322", "database": "InterPro" }, { "id": "mmu:228361", "url": "https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+mmu:228361", "database": "KEGG Pathway" }, { "id": "2443564", "url": "http://www.informatics.jax.org/marker/MGI:2443564", "database": "MGI" }, { "id": "PPAECCQ", "url": "https://omabrowser.org/oma/group/PPAECCQ/", "database": "OMA" }, { "id": "488527at2759", "url": "http://www.orthodb.org/?query=488527at2759", "database": "OrthoDB" }, { "id": "PR_A2AH22", "url": "http://purl.obolibrary.org/obo/PR_A2AH22", "database": "PRO" }, { "id": "R-MMU-1632852", "url": "https://www.reactome.org/PathwayBrowser/#R-MMU-1632852", "database": "Reactome" }, { "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223", "database": "RefSeq" }, { "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22", "database": "UniProtKB" }, { "id": "A2AH22-1", "url": "https://www.uniprot.org/uniprot/A2AH22-1", "database": "UniProtKB" }, { "id": "A2AH22-2", "url": "https://www.uniprot.org/uniprot/A2AH22-2", "database": "UniProtKB" }, { "id": "A2AH22-3", "url": "https://www.uniprot.org/uniprot/A2AH22-3", "database": "UniProtKB" }, { "id": "A2AH22-4", "url": "https://www.uniprot.org/uniprot/A2AH22-4", "database": "UniProtKB" }, { "id": "A2AH22-5", "url": "https://www.uniprot.org/uniprot/A2AH22-5", "database": "UniProtKB" }, { "id": "A2AH22-6", "url": "https://www.uniprot.org/uniprot/A2AH22-6", "database": "UniProtKB" }, { "id": "A2AH22-7", "url": "https://www.uniprot.org/uniprot/A2AH22-7", "database": "UniProtKB" } ], "sequence": { "sequence": "MKVVPEKNAVRILWGRERGTRAMGAQRLLQELVEDKTRWMKWEGKRVELPDSPRSTFLLAFSPDRTLLASTHVNHNIYITEVKTGKCVHSLIGHRRTPWCVTFHPTISGLIASGCLDGEVRIWDLHGGSESWFTDSNNAIASLAFHPTAQLLLIATANEIHFWDWSRREPFAVVKTASEMERVRLVRFDPLGHYLLTAIVNPSNQQGDDEPEIPIDGTELSHYRQRALLQSQPVRRTPLLHNFLHMLSSRSSGIQVGEQSTVQDSATPSPPPPPPQPSTERPRTSAYIRLRQRVSYPTTVECCQHPGILCLCSRCAGTRVPSLLPHQDSVPPASARATTPSFSFVQTEPFHPPEQASSTQQDQGLLNRPSAFSTVQSSTAGNTLRNLSLGPTRRSLGGPLSSHPSRYHRELAPGLTGSEWTRTVLTLNSRSEVESMPPPRTSASSVSLLSVLRQQEGGSQASVYTSATEGRGFPSSGLATESDGGNGSSQNNSGSIRHELQCDLRRFFLEYDRLQELDQSLSGETPQTQQAQEMLNNNIESERPGPSHLPTPHSSENNSNLSRGHLNRCRACHNLLTFNNDTLRWERTTPNYSSGEASSSWHVSTTFEGMPPSGNQLPPLERTEGQMPSSSRLELSSSASSQEERTVGVAFNQETGHWERIYTQSSRSGTVSQEALHQDMPEESSEEDSLRRRLLESSLISLSRYDGAGSREHPIYPDPARLSPAAYYAQRMIQYLSRRDSIRQRSMRYQQNRLRSSTSSSSSDNQGPSVEGTDLEFEDFEDNGDRSRHRAPRNARMSAPSLGRFVPRRFLLPEYLPYAGIFHERGQPGLATHSSVNRVLAGAVIGDGQSAVASNIANTTYRLQWWDFTKFDLPEISNASVNVLVQNCKIYNDASCDISADGQLLAAFIPSSQRGFPDEGILAVYSLAPHNLGEMLYTKRFGPNAISVSLSPMGRYVMVGLASRRILLHPSTEHMVAQVFRLQQAHGGETSMRRVFNVLYPMPADQRRHVSINSARWLPEPGLGLAYGTNKGDLVICRPEALNSGIEYYWDQLSETVFTVHSSSRSSERPGTSRATWRTDRDMGLMNAIGLQPRNPTTSVTSQGTQTLALQLQNAETQTEREEEEPGAASSGPGEGEGSEYGGSGEDALSRIQRLMAEGGMTAVVQREQSTTMASMGGFGNNIIVSHRIHRSSQTGTESGAARTSSPQPSTSRGLPSEPGQLAERALSPRTASWDQPSTSGRELPQPALSSSSPVPIPVPLASNEGPTMHCNVTNNSHLPEGDGSNRGEAAGPSGEPQNR", "length": 1300, "header": "sp|A2AH22-1|AMRA1_MOUSE Isoform 1 of Activating molecule in BECN1-regulated autophagy protein 1 OS=Mus musculus OX=10090 GN=Ambra1 PE=1 SV=1 CANONICAL=A2AH22-1" }, "isoforms": [ { "isoform_ac": "A2AH22-1", "url": "https://www.uniprot.org/uniprot/A2AH22#A2AH22-1", "sequence": { "sequence": "MKVVPEKNAVRILWGRERGTRAMGAQRLLQELVEDKTRWMKWEGKRVELPDSPRSTFLLAFSPDRTLLASTHVNHNIYITEVKTGKCVHSLIGHRRTPWCVTFHPTISGLIASGCLDGEVRIWDLHGGSESWFTDSNNAIASLAFHPTAQLLLIATANEIHFWDWSRREPFAVVKTASEMERVRLVRFDPLGHYLLTAIVNPSNQQGDDEPEIPIDGTELSHYRQRALLQSQPVRRTPLLHNFLHMLSSRSSGIQVGEQSTVQDSATPSPPPPPPQPSTERPRTSAYIRLRQRVSYPTTVECCQHPGILCLCSRCAGTRVPSLLPHQDSVPPASARATTPSFSFVQTEPFHPPEQASSTQQDQGLLNRPSAFSTVQSSTAGNTLRNLSLGPTRRSLGGPLSSHPSRYHRELAPGLTGSEWTRTVLTLNSRSEVESMPPPRTSASSVSLLSVLRQQEGGSQASVYTSATEGRGFPSSGLATESDGGNGSSQNNSGSIRHELQCDLRRFFLEYDRLQELDQSLSGETPQTQQAQEMLNNNIESERPGPSHLPTPHSSENNSNLSRGHLNRCRACHNLLTFNNDTLRWERTTPNYSSGEASSSWHVSTTFEGMPPSGNQLPPLERTEGQMPSSSRLELSSSASSQEERTVGVAFNQETGHWERIYTQSSRSGTVSQEALHQDMPEESSEEDSLRRRLLESSLISLSRYDGAGSREHPIYPDPARLSPAAYYAQRMIQYLSRRDSIRQRSMRYQQNRLRSSTSSSSSDNQGPSVEGTDLEFEDFEDNGDRSRHRAPRNARMSAPSLGRFVPRRFLLPEYLPYAGIFHERGQPGLATHSSVNRVLAGAVIGDGQSAVASNIANTTYRLQWWDFTKFDLPEISNASVNVLVQNCKIYNDASCDISADGQLLAAFIPSSQRGFPDEGILAVYSLAPHNLGEMLYTKRFGPNAISVSLSPMGRYVMVGLASRRILLHPSTEHMVAQVFRLQQAHGGETSMRRVFNVLYPMPADQRRHVSINSARWLPEPGLGLAYGTNKGDLVICRPEALNSGIEYYWDQLSETVFTVHSSSRSSERPGTSRATWRTDRDMGLMNAIGLQPRNPTTSVTSQGTQTLALQLQNAETQTEREEEEPGAASSGPGEGEGSEYGGSGEDALSRIQRLMAEGGMTAVVQREQSTTMASMGGFGNNIIVSHRIHRSSQTGTESGAARTSSPQPSTSRGLPSEPGQLAERALSPRTASWDQPSTSGRELPQPALSSSSPVPIPVPLASNEGPTMHCNVTNNSHLPEGDGSNRGEAAGPSGEPQNR", "length": 1300, "header": "sp|A2AH22-1|AMRA1_MOUSE Isoform 1 of Activating molecule in BECN1-regulated autophagy protein 1 OS=Mus musculus OX=10090 GN=Ambra1 PE=1 SV=1 CANONICAL=A2AH22-1" }, "locus": { "chromosome": "2", "start_pos": 91748165, "end_pos": 91596911, "strand": "-", "evidence": [ { "database": "Ensembl Transcript", "id": "ENSMUST00000045705", "url": "https://www.ensembl.org/id/ENSMUST00000045705" }, { "database": "Ensembl Peptide", "id": "ENSMUSP00000049258", "url": "https://www.ensembl.org/id/ENSMUSP00000049258" } ] } }, { "isoform_ac": "A2AH22-2", "url": "https://www.uniprot.org/uniprot/A2AH22#A2AH22-2", "sequence": { "sequence": "MKVVPEKNAVRILWGRERGTRAMGAQRLLQELVEDKTRWMKWEGKRVELPDSPRSTFLLAFSPDRTLLASTHVNHNIYITEVKTGKCVHSLIGHRRTPWCVTFHPTISGLIASGCLDGEVRIWDLHGGSESWFTDSNNAIASLAFHPTAQLLLIATANEIHFWDWSRREPFAVVKTASEMERVRLVRFDPLGHYLLTAIVNPSNQQGDDEPEIPIDGTELSHYRQRALLQSQPVRRTPLLHNFLHMLSSRSSGIQTEPFHPPEQASSTQQDQGLLNRPSAFSTVQSSTAGNTLRNLSLGPTRRSLGGPLSSHPSRYHRELAPGLTGSEWTRTVLTLNSRSEVESMPPPRTSASSVSLLSVLRQQEGGSQASVYTSATEGRGFPSSGLATESDGGNGSSQNNSGSIRHELQCDLRRFFLEYDRLQELDQSLSGETPQTQQAQEMLNNNIESERPGPSHLPTPHSSENNSNLSRGHLNRCRACHNLLTFNNDTLRWERTTPNYSSGEASSSWHVSTTFEGMPPSGNQLPPLERTEGQMPSSSRLELSSSASSQEERTVGVAFNQETGHWERIYTQSSRSGTVSQEALHQDMPEESSEEDSLRRRLLESSLISLSRYDGAGSREHPIYPDPARLSPAAYYAQRMIQYLSRRDSIRQRSMRYQQNRLRSSTSSSSSDNQGPSVEGTDLEFEDFEDNGDRSRHRAPRNARMSAPSLGRFVPRRFLLPEYLPYAGIFHERGQPGLATHSSVNRVLAGAVIGDGQSAVASNIANTTYRLQWWDFTKFDLPEISNASVNVLVQNCKIYNDASCDISADGQLLAAFIPSSQRGFPDEGILAVYSLAPHNLGEMLYTKRFGPNAISVSLSPMGRYVMVGLASRRILLHPSTEHMVAQVFRLQQAHGGETSMRRVFNVLYPMPADQRRHVSINSARWLPEPGLGLAYGTNKGDLVICRPEALNSGIEYYWDQLSETVFTVHSSSRSSERPGTSRATWRTDRDMGLMNAIGLQPRNPTTSVTSQGTQTLALQLQNAETQTEREEEEPGAASSGPGEGEGSEYGGSGEDALSRIQRLMAEGGMTAVVQREQSTTMASMGGFGNNIIVSHRIHRSSQTGTESGAARTSSPQPSTSRGLPSEPGQLAERALSPRTASWDQPSTSGRELPQPALSSSSPVPIPVPLASNEGPTMHCNVTNNSHLPEGDGSNRGEAAGPSGEPQNR", "length": 1209, "header": "sp|A2AH22-2|AMRA1_MOUSE Isoform 2 of Activating molecule in BECN1-regulated autophagy protein 1 OS=Mus musculus OX=10090 GN=Ambra1 PE=1 SV=1 CANONICAL=A2AH22-1" }, "locus": { "chromosome": "2", "start_pos": 91748165, "end_pos": 91596911, "strand": "-", "evidence": [ { "database": "Ensembl Transcript", "id": "ENSMUST00000099712", "url": "https://www.ensembl.org/id/ENSMUST00000099712" }, { "database": "Ensembl Peptide", "id": "ENSMUSP00000097299", "url": "https://www.ensembl.org/id/ENSMUSP00000097299" } ] } }, { "isoform_ac": "A2AH22-3", "url": "https://www.uniprot.org/uniprot/A2AH22#A2AH22-3", "sequence": { "sequence": "MKVVPEKNAVRILWGRERGTRAMGAQRLLQELVEDKTRWMKWEGKRVELPDSPRSTFLLAFSPDRTLLASTHVNHNIYITEVKTGKCVHSLIGHRRTPWCVTFHPTISGLIASGCLDGEVRIWDLHGGSESWFTDSNNAIASLAFHPTAQLLLIATANEIHFWDWSRREPFAVVKTASEMERVRLVRFDPLGHYLLTAIVNPSNQQGDDEPEIPIDGTELSHYRQRALLQSQPVRRTPLLHNFLHMLSSRSSGIQVGEQSTVQDSATPSPPPPPPQPSTERPRTSAYIRLRQRVSYPTTVECCQHPGILCLCSRCAGTRVPSLLPHQDSVPPASARATTPSFSFVQTEPFHPPEQASSTQQDQGLLNRPSAFSTVQSSTAGNTLRNLSLGPTRRSLGGPLSSHPSRYHRELAPGLTGSEWTRTVLTLNSRSEVESMPPPRTSASSVSLLSVLRQQEGGSQASVYTSATEGRGFPSSGLATESDGGNGSSQNNSGSIRHELQCDLRRFFLEYDRLQELDQSLSGETPQTQQAQEMLNNNIESERPGPSHLPTPHSSENNSNLSRGHLNRCRACHNLLTFNNDTLRWERTTPNYSSGEASSSWHVSTTFEGMPPSGNQLPPLERTEGQMPSSSRLELSSSASSQEERTVGVAFNQETGHWERIYTQSSRSGTVSQEALHQDMPEESSEEDSLRRRLLESSLISLSRYDGAGSREHPIYPDPARLSPAAYYAQRMIQYLSRRDSIRQRSMRYQQNRLRSSTSSSSSDNQGPSVEGTDLEFEDFE", "length": 781, "header": "sp|A2AH22-3|AMRA1_MOUSE Isoform 3 of Activating molecule in BECN1-regulated autophagy protein 1 OS=Mus musculus OX=10090 GN=Ambra1 PE=1 SV=1 CANONICAL=A2AH22-1" }, "locus": {} }, { "isoform_ac": "A2AH22-4", "url": "https://www.uniprot.org/uniprot/A2AH22#A2AH22-4", "sequence": { "sequence": "MKVVPEKNAVRILWGRERGTRAMGAQRLLQELVEDKTRWMKWEGKRVELPDSPRSTFLLAFSPDRTLLASTHVNHNIYITEVKTGKCVHSLIGHRRTPWCVTFHPTISGLIASGCLDGEVRIWDLHGGSESWFTDSNNAIASLAFHPTAQLLLIATANEIHFWDWSRREPFAVVKTASEMERVRLVRFDPLGHYLLTAIVNPSNQQGDDEPEIPIDGTELSHYRQRALLQSQPVRRTPLLHNFLHMLSSRSSGIQVGEQSTVQDSATPSPPPPPPQPSTERPRTSAYIRLRQRVSYPTTVECCQHPGILCLCSRCAGTRVPSLLPHQDSVPPASARATTPSFSFVQTEPFHPPEQASSTQQDQGLLNRPSAFSTVQSSTAGNTLRNLSLGPTRRSLGGPLSSHPSRYHRELAPGLTGSEWTRTVLTLNSRSEVESMPPPRTSASSVSLLSVLRQQEGGSQASVYTSATEGRGFPSSGLATESDGGNGSSQNNSGSIRHELQCDLRRFFLEYDRLQELDQSLSGETPQTQQAQEMLNNNIESERPGPSHLPTPHSSENNSNLSRGHLNRCRACHNLLTFNNDTLRWERTTPNYSSGEASSSWHVSTTFEGMPPSGNQLPPLERTEGQMPSSSRLELSSSASSQEERTVGVAFNQETGHWERIYTQSSRSGTVSQEALHQDMPEESSEEDSLRRLSPAAYYAQRMIQYLSRRDSIRQRSMRYQQNRLRSSTSSSSSDNQGPSVEGTDLEFEDFE", "length": 752, "header": "sp|A2AH22-4|AMRA1_MOUSE Isoform 4 of Activating molecule in BECN1-regulated autophagy protein 1 OS=Mus musculus OX=10090 GN=Ambra1 PE=1 SV=1 CANONICAL=A2AH22-1" }, "locus": {} }, { "isoform_ac": "A2AH22-5", "url": "https://www.uniprot.org/uniprot/A2AH22#A2AH22-5", "sequence": { "sequence": "MKVVPEKNAVRILWGRERGTRAMGAQRLLQELVEDKTRWMKWEGKRVELPDSPRSTFLLAFSPDRTLLASTHVNHNIYITEVKTGKCVHSLIGHRRTPWCVTFHPTISGLIASGCLDGEVRIWDLHGGSESWFTDSNNAIASLAFHPTAQLLLIATANEIHFWDWSRREPFAVVKTASEMERVRLVRFDPLGHYLLTAIVNPSNQQGDDEPEIPIDGTELSHYRQRALLQSQPVRRTPLLHNFLHMLSSRSSGIQTEPFHPPEQASSTQQDQGLLNRPSAFSTVQSSTAGNTLRNLSLGPTRRSLGGPLSSHPSRYHRELAPGLTGSEWTRTVLTLNSRSEVESMPPPRTSASSVSLLSVLRQQEGGSQASVYTSATEGRGFPSSGLATESDGGNGSSQNNSGSIRHELQCDLRRFFLEYDRLQELDQSLSGETPQTQQAQEMLNNNIESERPGPSHLPTPHSSENNSNLSRGHLNRCRACHNLLTFNNDTLRWERTTPNYSSGEASSSWHVSTTFEGMPPSGNQLPPLERTEGQMPSSSRLELSSSASSQEERTVGVAFNQETGHWERIYTQSSRSGTVSQEALHQDMPEESSEEDSLRRLSPAAYYAQRMIQYLSRRDSIRQRSMRYQQNRLRSSTSSSSSDNQGPSVEGTDLEFEDFEDNGDRSRHRAPRNARMSAPSLGRFVPRRFLLPEYLPYAGIFHERGQPGLATHSSVNRVLAGAVIGDGQSAVASNIANTTYRLQWWDFTKFDLPEISNASVNVLVQNCKIYNDASCDISADGQLLAAFIPSSQRGFPDEGILAVYSLAPHNLGEMLYTKRFGPNAISVSLSPMGRYVMVGLASRRILLHPSTEHMVAQVFRLQQAHGGETSMRRVFNVLYPMPADQRRHQRSTSLK", "length": 896, "header": "sp|A2AH22-5|AMRA1_MOUSE Isoform 5 of Activating molecule in BECN1-regulated autophagy protein 1 OS=Mus musculus OX=10090 GN=Ambra1 PE=1 SV=1 CANONICAL=A2AH22-1" }, "locus": {} }, { "isoform_ac": "A2AH22-6", "url": "https://www.uniprot.org/uniprot/A2AH22#A2AH22-6", "sequence": { "sequence": "MKVVPEKNAVRILWGRERGTRAMGAQRLLQELVEDKTRWMKWEGKRVELPDSPRSTFLLAFSPDRTLLASTHVNHNIYITEVKTGKCVHSLIGHRRTPWCVTFHPTISGLIASGCLDGEVRIWDLHGGSESWFTDSNNAIASLAFHPTAQLLLIATANEIHFWDWSRREPFAVVKTASEMERVRLVRFDPLGHYLLTAIVNPSNQQGDDEPEIPIDGTELSHYRQRALLQSQPVRRTPLLHNFLHMLSSRSSGIQVGEQSTVQDSATPSPPPPPPQPSTERPRTSAYIRLRQRVSYPTTVECCQHPGILCLCSRCAGTRVPSLLPHQDSVPPASARATTPSFSFVQTEPFHPPEQASSTQQDQGLLNRPSAFSTVQSSTAGNTLRNLSLGPTRRSLGGPLSSHPSRYHRELAPGLTGSEWTRTVLTLNSRSEVESMPPPRTSASSVSLLSVLRQQEGGSQASVYTSATEGRGFPSSGLATESDGGNGSSQNNSGSIRHELQCDLRRFFLEYDRLQELDQSLSGETPQTQQAQEMLNNNIESERPGPSHLPTPHSSENNSNLSRGHLNRCRACHNLLTFNNDTLRWERTTPNYSSGEASSSWHVSTTFEGMPPSGNQLPPLERTEGQMPSSSRLELSSSASSQEERTVGVAFNQETGHWERIYTQSSRSGTVSQEALHQDMPEESSEEDSLRRRLLESSLISLSRYDGAGSREHPIYPDPARDNGDRSRHRAPRNARMSAPSLGRFVPRRFLLPEYLPYAGIFHERGQPGLATHSSVNRVLAGAVIGDGQSAVASNIANTTYRLQWWDFTKFDLPEISNASVNVLVQNCKIYNDASCDISADGQLLAAFIPSSQRGFPDEGILAVYSLAPHNLGEMLYTKRFGPNAISVSLSPMGRYVMVGLASRRILLHPSTEHMVAQVFRLQQAHGGETSMRRVFNVLYPMPADQRRHVSINSARWLPEPGLGLAYGTNKGDLVICRPEALNSGIEYYWDQLSETVFTVHSSSRSSERPGTSRATWRTDRDMGLMNAIGLQPRNPTTSVTSQGTQTLALQLQNAETQTEREEEEPGAASSGPGEGEGSEYGGSGEDALSRIQRLMAEGGMTAVVQREQSTTMASMGGFGNNIIVSHRIHRSSQTGTESGAARTSSPQPSTSRGLPSEPGQLAERALSPRTASWDQPSTSGRELPQPALSSSSPVPIPVPLASNEGPTMHCNVTNNSHLPEGDGSNRGEAAGPSGEPQNR", "length": 1240, "header": "sp|A2AH22-6|AMRA1_MOUSE Isoform 6 of Activating molecule in BECN1-regulated autophagy protein 1 OS=Mus musculus OX=10090 GN=Ambra1 PE=1 SV=1 CANONICAL=A2AH22-1" }, "locus": { "chromosome": "2", "start_pos": 91748165, "end_pos": 91596911, "strand": "-", "evidence": [ { "database": "Ensembl Transcript", "id": "ENSMUST00000111316", "url": "https://www.ensembl.org/id/ENSMUST00000111316" }, { "database": "Ensembl Peptide", "id": "ENSMUSP00000106948", "url": "https://www.ensembl.org/id/ENSMUSP00000106948" } ] } }, { "isoform_ac": "A2AH22-7", "url": "https://www.uniprot.org/uniprot/A2AH22#A2AH22-7", "sequence": { "sequence": "MKVVPEKNAVRILWGRERGTRAMGAQRLLQELVEDKTRWMKWEGKRVELPDSPRSTFLLAFSPDRTLLASTHVNHNIYITEVKTGKCVHSLIGHRRTPWCVTFHPTISGLIASGCLDGEVRIWDLHGGSESWFTDSNNAIASLAFHPTAQLLLIATANEIHFWDWSRREPFAVVKTASEMERVRLVRFDPLGHYLLTAIVNPSNQQGDDEPEIPIDGTELSHYRQRALLQSQPVRRTPLLHNFLHMLSSRSSGIQTEPFHPPEQASSTQQDQGLLNRPSAFSTVQSSTAGNTLRNLSLGPTRRSLGGPLSSHPSRYHRELAPGLTGSEWTRTVLTLNSRSEVESMPPPRTSASSVSLLSVLRQQEGGSQASVYTSATEGRGFPSSGLATESDGGNGSSQNNSGSIRHELQCDLRRFFLEYDRLQELDQSLSGETPQTQQAQEMLNNNIESERPGPSHLPTPHSSENNSNLSRGHLNRCRACHNLLTFNNDTLRWERTTPNYSSGEASSSWHVSTTFEGMPPSGNQLPPLERTEGQMPSSSRLELSSSASSQEERTVGVAFNQETGHWERIYTQSSRSGTVSQEALHQDMPEESSEEDSLRRLSPAAYYAQRMIQYLSRRDSIRQRSMRYQQNRLRSSTSSSSSDNQGPSVEGTDLEFEDFEDNGDRSRHRAPRNARMSAPSLGRFVPRRFLLPEYLPYAGIFHERGQPGLATHSSVNRVLAGAVIGDGQSAVASNIANTTYRLQWWDFTKFDLPEISNASVNVLVQNCKIYNDASCDISADGQLLAAFIPSSQRGFPDEGILAVYSLAPHNLGEMLYTKRFGPNAISVSLSPMGRYVMVGLASRRILLHPSTEHMVAQVFRLQQAHGGETSMRRVFNVLYPMPADQRRHVSINSARWLPEPGLGLAYGTNKGDLVICRPEALNSGIEYYWDQLSETVFTVHSSSRSSERPGTSRATWRTDRDMGLMNAIGLQPRNPTTSVTSQGTQTLALQLQNAETQTEREEEEPGAASSGPGEGEGSEYGGSGEDALSRIQRLMAEGGMTAVVQREQSTTMASMGGFGNNIIVSHRIHRSSQTGTESGAARTSSPQPSTSRGLPSEPGQLAERALSPRTASWDQPSTSGRELPQPALSSSSPVPIPVPLASNEGPTMHCNVTNNSHLPEGDGSNRGEAAGPSGEPQNR", "length": 1180, "header": "sp|A2AH22-7|AMRA1_MOUSE Isoform 7 of Activating molecule in BECN1-regulated autophagy protein 1 OS=Mus musculus OX=10090 GN=Ambra1 PE=1 SV=1 CANONICAL=A2AH22-1" }, "locus": { "chromosome": "2", "start_pos": 91748165, "end_pos": 91596911, "strand": "-", "evidence": [ { "database": "Ensembl Transcript", "id": "ENSMUST00000045699", "url": "https://www.ensembl.org/id/ENSMUST00000045699" }, { "database": "Ensembl Peptide", "id": "ENSMUSP00000048898", "url": "https://www.ensembl.org/id/ENSMUSP00000048898" } ] } } ], "glycosylation": [], "phosphorylation": [ { "start_pos": 1044, "end_pos": 1044, "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "", "residue": "Ser", "comment": "Phosphoserine", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ] }, { "start_pos": 1206, "end_pos": 1206, "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "", "residue": "Ser", "comment": "Phosphoserine", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ] }, { "start_pos": 329, "end_pos": 329, "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "", "residue": "Ser", "comment": "Phosphoserine", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ] }, { "start_pos": 395, "end_pos": 395, "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "", "residue": "Ser", "comment": "Phosphoserine", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ] }, { "start_pos": 444, "end_pos": 444, "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "", "residue": "Ser", "comment": "Phosphoserine", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ] }, { "start_pos": 52, "end_pos": 52, "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "", "residue": "Ser", "comment": "Phosphoserine", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ] }, { "start_pos": 636, "end_pos": 636, "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "", "residue": "Ser", "comment": "Phosphoserine", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ] }, { "start_pos": 640, "end_pos": 640, "kinase_uniprot_canonical_ac": "", "kinase_gene_name": "", "residue": "Ser", "comment": "Phosphoserine", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ] } ], "glycation": [], "keywords": [], "publication": [ { "title": "Ambra1 regulates autophagy and development of the nervous system.", "journal": "Nature", "date": "2007", "authors": "Cecconi F., Piacentini M., Chowdhury K., Corazzari M., Di Bartolomeo S., Fuoco C., Giunta L., Gruss P., Maria Fimia G., Nardacci R., Romagnoli A., Schwartz P., Stoykova A., Ucar A.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" } ], "reference": [ { "type": "PubMed", "id": "17589504", "url": "https://glygen.org/publication/PubMed/17589504" } ] }, { "title": "Autophagy: a new regulator of development.", "journal": "Nat. Cell Biol.", "date": "2007", "authors": "Le Bot N.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "reference": [ { "type": "PubMed", "id": "17603510", "url": "https://glygen.org/publication/PubMed/17603510" } ] }, { "title": "Parkin interacts with Ambra1 to induce mitophagy.", "journal": "J. Neurosci.", "date": "2011", "authors": "De Strooper B., Gevaert K., Mandemakers W., Vandenberghe W., Cornelissen T., Van Humbeeck C., Hofkens H.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" } ], "reference": [ { "type": "PubMed", "id": "21753002", "url": "https://glygen.org/publication/PubMed/21753002" } ] }, { "title": "WASH inhibits autophagy through suppression of Beclin 1 ubiquitination.", "journal": "EMBO J.", "date": "2013", "authors": "Li C., Li L., Sun L., Wang S., Yang X., Zhao Z., Dai Z., Shi L., Cheng X., Fan Z., Huang G., Sun Q., Ye B., Du Y., Xia P., Hou N.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "reference": [ { "type": "PubMed", "id": "23974797", "url": "https://glygen.org/publication/PubMed/23974797" } ] }, { "title": "Functional interaction between autophagy and ciliogenesis.", "journal": "Nature", "date": "2013", "authors": "Codogno P., Patel B., Beau I., Cuervo A.M., Diaz-Carretero A., Orhon I., Pampliega O., Satir B.H., Satir P., Sridhar S.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "reference": [ { "type": "PubMed", "id": "24089209", "url": "https://glygen.org/publication/PubMed/24089209" } ] }, { "title": "Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.", "journal": "Mol. Cell. Proteomics", "date": "2014", "authors": "Beausoleil S.A., Wang Y., Zhou J., Comb M.J., Guo A., Lee K.A., Aguiar M., Bedford M.T., Gu H., Jia X., Kornhauser J., Mulhern D., Ren J., Silva J.C., Vemulapalli V., Yang V.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "reference": [ { "type": "PubMed", "id": "24129315", "url": "https://glygen.org/publication/PubMed/24129315" } ] }, { "title": "RNF2 is recruited by WASH to ubiquitinate AMBRA1 leading to downregulation of autophagy.", "journal": "Cell Res.", "date": "2014", "authors": "Li M., Wang S., Fan Z., Zhu P., Huang G., Du Y., Xia P.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "reference": [ { "type": "PubMed", "id": "24980959", "url": "https://glygen.org/publication/PubMed/24980959" } ] }, { "title": "AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1.", "journal": "Cell Death Differ.", "date": "2015", "authors": "Cecconi F., Fimia G.M., Piacentini M., Nardacci R., Romagnoli A., Campanella M., Corrado M., Campello S., Cianfanelli V., Nazio F., Strappazzon F.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "reference": [ { "type": "PubMed", "id": "25215947", "url": "https://glygen.org/publication/PubMed/25215947" } ] }, { "title": "AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation.", "journal": "Nat. Cell Biol.", "date": "2015", "authors": "Salazar M., Bordi M., Cecconi F., De Zio D., Fimia G.M., Piacentini M., Di Bartolomeo S., Fuoco C., Dengjel J., Velasco G., Rohde M., Quondamatteo F., Cianfanelli V., Nazio F., Antonioli M., Gretzmeier C., D'Orazio M., Dalla Valle L., Gherardini P.F., Helmer-Citterich M., Lorente M., Skobo T.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "reference": [ { "type": "PubMed", "id": "25438055", "url": "https://glygen.org/publication/PubMed/25438055" } ] }, { "title": "AMBRA1 is involved in T cell receptor-mediated metabolic reprogramming through an ATG7-independent pathway.", "journal": "Biochem. Biophys. Res. Commun.", "date": "2017", "authors": "Sato T., Suzuki T., Iida Y., Tanaka M., Okada Y., Kimura M., Inoue I., Hosomichi K., Akatsuka H., Ohtsuka M., Okada C., Masuhara K., Davaadorj O., Fukunishi N., Kuga S.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "reference": [ { "type": "PubMed", "id": "28789945", "url": "https://glygen.org/publication/PubMed/28789945" } ] }, { "title": "AMBRA1 controls regulatory T-cell differentiation and homeostasis upstream of the FOXO3-FOXP3 axis.", "journal": "Dev. Cell", "date": "2018", "authors": "Weber G., Cecconi F., Fimia G.M., Bonaldo P., Centonze D., Locatelli F., Ciccosanti F., La Rocca C., Matarese G., Procaccini C., Botti G., D'Amelio M., Ruffini F., Braghetta P., Becher J., Battistini L., Borsellino G., Campello S., Cianfanelli V., Nazio F., Strappazzon F., D'Acunzo P., Caruana I., Chrisam M., De Bardi M., Furlan R., Gigantino V., Mandolesi G., Martino G., Simula L., Volpe E.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "reference": [ { "type": "PubMed", "id": "30513302", "url": "https://glygen.org/publication/PubMed/30513302" } ] }, { "title": "The autophagy protein Ambra1 regulates gene expression by supporting novel transcriptional complexes.", "journal": "J. Biol. Chem.", "date": "2020", "authors": "Frame M.C., von Kriegsheim A., Byron A., Griffith B., Loftus A., Munro A.F., Schoenherr C., Wills J.C.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "reference": [ { "type": "PubMed", "id": "32616651", "url": "https://glygen.org/publication/PubMed/32616651" } ] }, { "title": "AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity.", "journal": "Nature", "date": "2021", "authors": "Bartek J., Lanzetti L., Bordi M., Cecconi F., De Zio D., Gallo A., Pagano M., Velasco G., Bartolazzi A., Swanton C., Bartkova J., Jeong Y.T., Locatelli F., Papaleo E., Montagna C., Filomeni G., Maya-Mendoza A., Sears R.C., Campello S., Cianfanelli V., Nazio F., D'Acunzo P., Maiani E., Milletti G., Rona G., Simoneschi D., Carinci M., Cesarini V., Daniel C.J., De Stefanis C., Di Leo L., Di Marco M., Gabicagogeascoa E., Hamerlik P., Holdgaard S.G., Hynds R.E., Lorente M., Merchut-Maya J.M., O'sullivan A., Pearce D.R., Pupo E., Raciti M., Rasmussen R., Rizza S., Russo F., Salvador N.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" } ], "reference": [ { "type": "PubMed", "id": "33854232", "url": "https://glygen.org/publication/PubMed/33854232" } ] }, { "title": "CRL4AMBRA1 is a master regulator of D-type cyclins.", "journal": "Nature", "date": "2021", "authors": "Jiang S., Cecconi F., Pagano M., Jones D.R., Busino L., Zhou N., Jeong Y.T., Arbini A.A., Cianfanelli V., Nazio F., Boccalatte F., Fenyoe D., Keegan S., Maiani E., Milletti G., Nithikasem S., O'Sullivan A., Rona G., Simoneschi D., Siu Y., Wang A.A.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" } ], "reference": [ { "type": "PubMed", "id": "33854235", "url": "https://glygen.org/publication/PubMed/33854235" } ] }, { "title": "The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D.", "journal": "Nature", "date": "2021", "authors": "Li C., Murray C.W., Demeter J., Yoshida A., Krogan N.J., Johnson J.R., He A., Cheng R., Chen S.H., Jackson P.K., Sage J., Diehl J.A., Lee M.C., Srinivasan P., Newton B.W., Kong C., Bassik M.C., Curtis C., Winslow M.M., Jeng E.E., Swaney D.L., Chaikovsky A.C., Drainas A.P., Hipkins S.Q., Loebell S., McCrea E., Petrov D.A., Poltorack C.D., Seoane J.A., Shue Y.T.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" } ], "reference": [ { "type": "PubMed", "id": "33854239", "url": "https://glygen.org/publication/PubMed/33854239" } ] }, { "title": "Loss of Ambra1 promotes melanoma growth and invasion.", "journal": "Nature communications", "date": "2021", "authors": "Di Leo L, Bodemeyer V, Bosisio FM, Claps G, Carretta M, Rizza S, Faienza F, Frias A, Khan S, Bordi M, Pacheco MP, Di Martino J, Bravo-Cordero JJ, Daniel CJ, Sears RC, Donia M, Madsen DH, Guldberg P, Filomeni G, Sauter T, Robert C, De Zio D, Cecconi F", "evidence": [ { "database": "RefSeq", "id": "NP_001074223", "url": "https://www.ncbi.nlm.nih.gov/protein/NP_001074223" } ], "reference": [ { "type": "PubMed", "id": "33953176", "url": "https://glygen.org/publication/PubMed/33953176" } ] } ], "pathway": [ { "id": "mmu:228361", "name": "", "url": "https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+mmu:228361", "resource": "KEGG Pathway" }, { "id": "R-MMU-1632852", "name": "Macroautophagy", "url": "https://www.reactome.org/PathwayBrowser/#R-MMU-1632852", "resource": "Reactome", "description": "Macroautophagy" } ], "orthologs": [ { "uniprot_canonical_ac": "F1LNQ2-1", "protein_name": "Autophagy and beclin 1 regulator 1", "gene_name": "Ambra1", "tax_id": 10116, "organism": "Rattus norvegicus", "sequence": { "sequence": "MKVVPEKNAVRILWGRERGTRAMGAQRLLQELVEDKTRWMKWEGKRVELPDSPTLDFLLAFSPDRTLLASTHVNHNIYITEVKTGKCVHSLIGHRRTPWCVTFHPTISGLIASGCLDGEVRIWDLHGGSESWFTDSNNAIASLAFHPTAQLLLIATANEIHFWDWSRREPFAVVKTASEMERVRLVRFDPLGHYLLTAIVNPSNQQGDDEPEIPIDGTELSHYRQRALLQSQPVRRTPLLHNFLHMLSSRSSGIQVGEQSTVQDSATPSPPPPPPQPSTERPRTSAYIRLRQRVSYPTTVECCQHPGILCLCSRCAGTRVPSLLPHQDSVPPASARATTPSFSFVQTEPFHPPEQASSTQQDQGLLNRPSAFSTVQSSTAGNTLRNLSLGPTRRSLGGPLSSHPSRYHRELAPGLTGSEWTRTVLTLNSRSEVESMPPPRTSASSVSLLSVLRQQEGGSQASVYTSATEGRGFPSSGLATESDGGNGSSQNNSGNIRHELQCDLRRFFLEYDRLQELDQSLSGETPQTQQAQEMLNNNIESERPGPSHQPTPHSSENNSNLSRGHLNRCRACHNLLTFNNDTLRWERTTPNYSSGEASSSWHVSTTFEGMPPSGNQLPPLERTEGQMPNSSRLELSSSASSQEERTVGVAFNQETGHWERIYTQSSRSGTVSQEALHQDMPEESSEEDSLRRRLLESSLISLSRYDGAGSREHPIYPDPARLSPAAYYAQRMIQYLSRRDSIRQRSMRYQQNRLRSSTSSSSSDNQGPSVEGTDLEFEDFEDNGDRSRHRAPRNARMSAPSLGRFVPRRFLLPEYLPYAGIFHERGQPGLATHSSVNRVLAGAVIGDGQSAVASNIANTTYRLQWWDFTKFDLPEISNASVNVLVQNCKIYNDASCDISADGQLLAAFIPSSQRGFPDEGILAVYSLAPHNLGEMLYTKRFGPNAISVSLSPMGRYVMVGLASRRILLHPSTEHMVAQVFRLQQAHGGETSMRRVFNVLYPMPADQRRHVSINSARWLPEPGLGLAYGTNKGDLVICRPEALNSGIEYYWDQLNETVFTVHSSSRSSERPGTSRATWRTDRDMGLMNAIGLQPRNPTTSVTSQGTQTLALQLQNAETQTEREEEEPGTASSGPGEGEGSEYGGSGEDALSRIQRLMAEGGMTAVVQREQSTTMASMGGFGNNIIVSHRIHRSSQTGTESGAARTSSPQPSTSRGLLSEPGQLAERGLSPRTASWDQPSTSGRELPQPALSSSSPVPIPVPLASNEGPTMHCNVTNNSHLPEGDSSNVGEAAGPSGEPRNR", "length": 1300 }, "evidence": [ { "id": "18204", "url": "http://www.informatics.jax.org/homology/18204", "database": "MGI" }, { "id": "A2AH22", "url": "https://omabrowser.org/oma/group/A2AH22/", "database": "OMA" } ], "common_name": "Rat" }, { "uniprot_canonical_ac": "Q9C0C7-1", "protein_name": "Activating molecule in BECN1-regulated autophagy protein 1", "gene_name": "AMBRA1", "tax_id": 9606, "organism": "Homo sapiens", "sequence": { "sequence": 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"length": 1298 }, "evidence": [ { "id": "18204", "url": "http://www.informatics.jax.org/homology/18204", "database": "MGI" }, { "id": "A2AH22", "url": "https://omabrowser.org/oma/group/A2AH22/", "database": "OMA" } ], "common_name": "Human" } ], "go_annotation": { "categories": [ { "name": "Biological Process", "total": 13, "go_terms": [ { "name": "autophagosome assembly", "id": "GO:0000045", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0000045", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" }, { "name": "negative regulation of cell population proliferation", "id": "GO:0008285", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0008285", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "17589504" }, { "name": "cell differentiation", "id": "GO:0030154", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0030154", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" }, { "name": "negative regulation of neuron apoptotic process", "id": "GO:0043524", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0043524", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "17589504" }, { "name": "autophagy", "id": "GO:0006914", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0006914", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "17589504" }, { "name": "neural tube development", "id": "GO:0021915", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0021915", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "17589504" }, { "name": "positive regulation of autophagy", "id": "GO:0010508", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0010508", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" }, { "name": "cellular response to starvation", "id": "GO:0009267", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0009267", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" }, { "name": "autophagy of mitochondrion", "id": "GO:0000422", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0000422", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" }, { "name": "mitophagy", "id": "GO:0000423", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0000423", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" }, { "name": "negative regulation of cardiac muscle cell apoptotic process", "id": "GO:0010667", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0010667", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" }, { "name": "positive regulation of phosphatidylinositol 3-kinase activity", "id": "GO:0043552", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0043552", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" }, { "name": "response to mitochondrial depolarisation", "id": "GO:0098780", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0098780", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" } ] }, { "name": "Cellular Component", "total": 7, "go_terms": [ { "name": "cytoplasm", "id": "GO:0005737", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005737", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "17589504" }, { "name": "mitochondrion", "id": "GO:0005739", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005739", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" }, { "name": "cytosol", "id": "GO:0005829", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005829", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "21753002" }, { "name": "intracellular membrane-bounded organelle", "id": "GO:0043231", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0043231", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "21873635" }, { "name": "phagocytic vesicle", "id": "GO:0045335", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0045335", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "22493499" }, { "name": "axoneme", "id": "GO:0005930", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005930", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "24089209" }, { "name": "autophagosome", "id": "GO:0005776", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0005776", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" } ] }, { "name": "Molecular Function", "total": 2, "go_terms": [ { "name": "ubiquitin protein ligase binding", "id": "GO:0031625", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0031625", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" }, { "name": "GTPase binding", "id": "GO:0051020", "url": "https://www.ebi.ac.uk/QuickGO/term/GO:0051020", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" } ], "pmid": "" } ] } ] }, "pro_annotation": [], "site_annotation": [ { "start_pos": 1272, "end_pos": 1274, "annotation": "n_glycosylation_sequon" }, { "start_pos": 1275, "end_pos": 1277, "annotation": "n_glycosylation_sequon" }, { "start_pos": 386, "end_pos": 388, "annotation": "n_glycosylation_sequon" }, { "start_pos": 486, "end_pos": 488, "annotation": "n_glycosylation_sequon" }, { "start_pos": 491, "end_pos": 493, "annotation": "n_glycosylation_sequon" }, { "start_pos": 557, "end_pos": 559, "annotation": "n_glycosylation_sequon" }, { "start_pos": 560, "end_pos": 562, "annotation": "n_glycosylation_sequon" }, { "start_pos": 580, "end_pos": 582, "annotation": "n_glycosylation_sequon" }, { "start_pos": 591, "end_pos": 593, "annotation": "n_glycosylation_sequon" }, { "start_pos": 858, "end_pos": 860, "annotation": "n_glycosylation_sequon" }, { "start_pos": 878, "end_pos": 880, "annotation": "n_glycosylation_sequon" } ], "ptm_annotation": [ { "annotation": "Phosphorylation at Ser-52 by MTOR inhibits its ability to regulate autophagy and mediate ubiquitination of ULK1. Phosphorylation by ULK1 in response to autophagy induction abolishes interaction with DYNLL1 and DYNLL2, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation. Phosphorylation by MTOR inhibits interaction with PPP2CA and subsequent dephosphorylation of MYC. Phosphorylation at Ser-1044 by CHUK/IKKA promotes its interaction with ATG8 family proteins GABARAP and MAP1LC3B and its mitophagic activity.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "PubMed", "id": "Q9C0C7", "url": "https://glygen.org/publication/PubMed/Q9C0C7" } ] }, { "annotation": "Ubiquitinated by RNF2 via 'Lys-48'-linkage in unstressed cells, leading to its degradation by the proteasome (PubMed:24980959). Induction of autophagy promotes stabilization via interaction with CUL4 (CUL4A or CUL4B) and DDB1. Upon prolonged starvation, ubiquitinated and degraded, terminating the autophagy response (By similarity).", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "PubMed", "id": "24980959", "url": "https://glygen.org/publication/PubMed/24980959" }, { "database": "PubMed", "id": "Q9C0C7", "url": "https://glygen.org/publication/PubMed/Q9C0C7" } ] }, { "annotation": "Undergoes proteolytic processing by caspase-6 (CASP6), caspase-7 (CASP7) and caspase-8 (CASP8) during apoptosis, resulting in the dismantling of the autophagic machinery and the accomplishment of the programmed cell death program. Also cleaved by calpains during apoptosis, which mediate a complete proteolytic degradation.", "evidence": [ { "database": "UniProtKB", "id": "A2AH22", "url": "https://www.uniprot.org/uniprot/A2AH22" }, { "database": "PubMed", "id": "Q9C0C7", "url": "https://glygen.org/publication/PubMed/Q9C0C7" } ] } ], "interactions": [], "reactions": [], "reaction_participants": [], "reaction_enzymes": [], "synthesized_glycans": [], "cluster_types": [ { "name": "isoformset.uniprotkb", "label": "Isoforms" }, { "name": "homologset.mgi", "label": "MGI Homologs" }, { "name": "homologset.oma", "label": "OMA Homologs" } ] }