{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q07912","secondaryAccessions":["Q6ZMQ0","Q8N6U7","Q96H59"],"uniProtkbId":"ACK1_HUMAN","entryAudit":{"firstPublicDate":"2003-10-24","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2009-05-05","entryVersion":242,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Activated CDC42 kinase 1"},"shortNames":[{"value":"ACK-1"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10652228"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16257963"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16472662"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18993068"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20333297"}],"value":"2.7.10.2"},{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16257963"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18993068"}],"value":"2.7.11.1"}]},"alternativeNames":[{"fullName":{"value":"Tyrosine kinase non-receptor protein 2"}}]},"genes":[{"geneName":{"value":"TNK2"},"synonyms":[{"value":"ACK1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10652228"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11278436"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16247015"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16257963"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16472662"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17038317"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18262180"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18435854"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19815557"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20110370"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20333297"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20383201"}],"value":"Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. 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Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP (PubMed:20110370)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:10596"},{"database":"Rhea","id":"RHEA-COMP:10136"},{"database":"Rhea","id":"RHEA-COMP:20101"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:46858"},{"database":"ChEBI","id":"CHEBI:61978"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.10.2","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU10028"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10652228"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16257963"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16472662"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18993068"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20333297"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:17989"},{"database":"Rhea","id":"RHEA-COMP:9863"},{"database":"Rhea","id":"RHEA-COMP:11604"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:29999"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:83421"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16257963"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18993068"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:46608"},{"database":"Rhea","id":"RHEA-COMP:11060"},{"database":"Rhea","id":"RHEA-COMP:11605"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30013"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:61977"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"2.7.11.1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16257963"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18993068"}]}},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10652228"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16257963"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20333297"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20383201"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20623637"}],"value":"Inhibited by AIM-100 (4-amino-5,6-biaryl-furo[2,3-d]pyrimidine), which suppresses activating phosphorylation at Tyr-284. Repressed by dasatinib"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10587647"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16137687"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16257963"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16288044"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17038317"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17494760"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18477472"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18993068"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19144635"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19815557"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20333297"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20979614"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21309750"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23686771"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8497321"}],"value":"Interacts with NEDD4 (via WW3 domain). NEDD4L and EGF promote association with NEDD4 (By similarity). Homodimer. Interacts with AR, CDC42, WWASL and WWOX. Interacts with CSPG4 (activated). Interacts with MERTK (activated); stimulates autophosphorylation. May interact (phosphorylated) with HSP90AB1; maintains kinase activity. Interacts with NPHP1. Interacts with SNX9 (via SH3 domain). Interacts with SRC (via SH2 and SH3 domain). Interacts with EGFR, and this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts (via kinase domain) with AKT1. Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with BCAR1/p130cas via SH3 domains. Forms complexes with GRB2 and numerous receptor tyrosine kinases (RTK) including LTK, AXL or PDGFRL, in which GRB2 promotes RTK recruitment by TNK2"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"P29972","geneName":"AQP1","intActId":"EBI-745213"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"P56945","geneName":"BCAR1","intActId":"EBI-702093"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"P60953-2","geneName":"CDC42","intActId":"EBI-287394"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"Q00610","geneName":"CLTC","intActId":"EBI-354967"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"P07902","geneName":"GALT","intActId":"EBI-750827"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"P62993","geneName":"GRB2","intActId":"EBI-401755"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"P08238","geneName":"HSP90AB1","intActId":"EBI-352572"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"Q9HC98","geneName":"NEK6","intActId":"EBI-740364"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"Q7Z3S9","geneName":"NOTCH2NLA","intActId":"EBI-945833"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"O60880","geneName":"SH2D1A","intActId":"EBI-6983382"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912","intActId":"EBI-603457"},"interactantTwo":{"uniProtKBAccession":"Q07912","geneName":"TNK2","intActId":"EBI-603457"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912-2","intActId":"EBI-11994780"},"interactantTwo":{"uniProtKBAccession":"A8MQ03","geneName":"CYSRT1","intActId":"EBI-3867333"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912-2","intActId":"EBI-11994780"},"interactantTwo":{"uniProtKBAccession":"Q9BQC3","geneName":"DPH2","intActId":"EBI-10237931"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912-2","intActId":"EBI-11994780"},"interactantTwo":{"uniProtKBAccession":"P07902","geneName":"GALT","intActId":"EBI-750827"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912-2","intActId":"EBI-11994780"},"interactantTwo":{"uniProtKBAccession":"Q92569","geneName":"PIK3R3","intActId":"EBI-79893"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912-2","intActId":"EBI-11994780"},"interactantTwo":{"uniProtKBAccession":"O60880","geneName":"SH2D1A","intActId":"EBI-6983382"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q07912-2","intActId":"EBI-11994780"},"interactantTwo":{"uniProtKBAccession":"O14796","geneName":"SH2D1B","intActId":"EBI-3923013"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O54967"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20333297"}],"value":"The Tyr-284 phosphorylated form is found both in the membrane and nucleus (By similarity). Co-localizes with EGFR on endosomes (PubMed:20333297). Nuclear translocation is CDC42-dependent (By similarity). 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It also shows a significant increase in expression in prostate cancers during the progressive stages"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"}],"value":"The EBD (EGFR-binding domain) domain is necessary for interaction with EGFR"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20979614"}],"value":"The SAM-like domain is necessary for NEDD4-mediated ubiquitination. 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