{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q00534","secondaryAccessions":["A4D1G0"],"uniProtkbId":"CDK6_HUMAN","entryAudit":{"firstPublicDate":"1993-04-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1993-04-01","entryVersion":246,"sequenceVersion":1},"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":"Cyclin-dependent kinase 6"},"ecNumbers":[{"value":"2.7.11.22"}]},"alternativeNames":[{"fullName":{"value":"Cell division protein kinase 6"}},{"fullName":{"value":"Serine/threonine-protein kinase PLSTIRE"}}]},"genes":[{"geneName":{"value":"CDK6"},"synonyms":[{"value":"CDKN6"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12833137"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14985467"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15254224"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15809340"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17420273"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17431401"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20333249"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20668294"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23918663"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8114739"}],"value":"Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663)"}],"commentType":"FUNCTION"},{"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":"2.7.11.22"}},{"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":"2.7.11.22"}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12833137"}],"value":"Inhibited by INK4 proteins (CDKN2C/p18-INK4c), aminopurvalanol, PD0332991, 4-(Pyrazol-4-yl)-pyrimidines and fisetin, a flavonol inhibitor. Activated by Thr-177 phosphorylation and Tyr-24 dephosphorylation (By similarity). Stimulated by cyclin from herpesvirus saimiri (V-cyclin/ECLF2). Rapidly down-regulated prior to cell differentiation (e.g. erythroid and osteoblast)"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11124804"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11828325"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15689157"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16096642"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16789739"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17431401"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20333249"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21038853"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8114739"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9482106"}],"value":"Interaction with D-type G1 cyclins. Cyclin binding promotes enzyme activation by phosphorylation at Thr-177 (By similarity). Binds to RUNX1, CDKN2D, FBXO7 and CDKN2C/p18-INK4c. Forms a cytoplasmic complex with Hsp90/HSP90AB1 and CDC37. FBXO7-binding promotes D-type cyclin binding. Interacts with Kaposi's sarcoma herpesvirus (KSHV) V-cyclin and herpesvirus saimiri (V-cyclin/ECLF2); the CDK6/V-cyclin complex phosphorylates NPM1 and thus lead to viral reactivation by reducing viral LANA levels"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"P41238","geneName":"APOBEC1","intActId":"EBI-12819523"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"Q8N5C1","geneName":"CALHM5","intActId":"EBI-21879592"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"P24385","geneName":"CCND1","intActId":"EBI-375001"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"P30281","geneName":"CCND3","intActId":"EBI-375013"},"numberOfExperiments":35,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"P51946","geneName":"CCNH","intActId":"EBI-741406"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"Q14094","geneName":"CCNI","intActId":"EBI-1104653"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"Q16543","geneName":"CDC37","intActId":"EBI-295634"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"P38936","geneName":"CDKN1A","intActId":"EBI-375077"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"P42771","geneName":"CDKN2A","intActId":"EBI-375053"},"numberOfExperiments":19,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"P42772","geneName":"CDKN2B","intActId":"EBI-711280"},"numberOfExperiments":19,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"P42773","geneName":"CDKN2C","intActId":"EBI-711290"},"numberOfExperiments":28,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"P55273","geneName":"CDKN2D","intActId":"EBI-745859"},"numberOfExperiments":28,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"Q08050-1","geneName":"FOXM1","intActId":"EBI-866499"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"P08238","geneName":"HSP90AB1","intActId":"EBI-352572"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"Q5XKR4","geneName":"OTP","intActId":"EBI-12865884"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"Q01196","geneName":"RUNX1","intActId":"EBI-925904"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"Q13485","geneName":"SMAD4","intActId":"EBI-347263"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"Q16629","geneName":"SRSF7","intActId":"EBI-398885"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q00534","intActId":"EBI-295663"},"interactantTwo":{"uniProtKBAccession":"Q9C019","geneName":"TRIM15","intActId":"EBI-2342111"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q64261"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23918663"}],"value":"Localized to the ruffling edge of spreading fibroblasts. Kinase activity only in nucleus. Localized to the cytosol of neurons and showed prominent staining around either side of the nucleus (By similarity). Present in the cytosol and in the nucleus in interphase cells and at the centrosome during mitosis from prophase to telophase (PubMed:23918663)"}]},"subcellularLocations":[{"location":{"value":"Cytoplasm","id":"SL-0086"}},{"location":{"value":"Nucleus","id":"SL-0191"}},{"location":{"value":"Cell projection, ruffle","id":"SL-0300"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23918663"}],"value":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome","id":"SL-0048"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20668294"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8114739"}],"value":"Expressed ubiquitously. Accumulates in squamous cell carcinomas, proliferating hematopoietic progenitor cells, beta-cells of pancreatic islets of Langerhans, and neuroblastomas. Reduced levels in differentiating cells"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16548883"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19139263"}],"value":"Down-regulated in response to enterovirus 71 (EV71) infection. Induced by NANOG during S-phase entry"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11828325"}],"value":"Thr-177 phosphorylation and Tyr-24 dephosphorylation promotes kinase activity"}],"commentType":"PTM"},{"texts":[{"value":"Genetic variations in CDK6 may influence stature as a quantitative trait, contributing to the stature quantitative trait locus 11 (STQTL11) [MIM:612223]. Adult height is an easily observable and highly heritable complex continuous trait. Because of this, it is a model trait for studying genetic influence on quantitative traits"}],"commentType":"POLYMORPHISM"},{"commentType":"DISEASE","disease":{"diseaseId":"Microcephaly 12, primary, autosomal recessive","diseaseAccession":"DI-04262","acronym":"MCPH12","description":"A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age-related mean. 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