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Details on Person UniProt:P11802 CDK4
| Class:Id | ReferenceGeneProduct:68329 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-303 added on Fri February 6 2015;initiator methionine:1 for 68329 removed on Fri Nov 03 2023;initiator methionine: for 68329 added on Fri Nov 03 2023;initiator methionine: for 68329 removed on Fri Aug 15 2025;initiator methionine:1 for 68329 added on Fri Aug 15 2025 |
| _displayName | UniProt:P11802 CDK4 |
| _timestamp | 2025-08-15 21:51:46 |
| chain | initiator methionine:1 chain:2-303 |
| checksum | 0916A0C07403A33A |
| comment | FUNCTION Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)ACTIVITY REGULATION Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequent activation.SUBUNIT Component of the D-CDK4 complex, composed of CDK4 and some D-type G1 cyclin (CCND1, CCND2 or CCND3). Interacts directly in the complex with CCND1, CCND2 or CCND3. Interacts with SEI1 and ZNF655. Forms a ternary complex, cyclin D-CDK4-CDKN1B, involved in modulating CDK4 enzymatic activity. Interacts directly with CDKN1B (phosphorylated on 'Tyr-88' and 'Tyr-89'); the interaction allows assembly of the cyclin D-CDK4 complex, Thr-172 phosphorylation, nuclear translocation and enhances the cyclin D-CDK4 complex activity. CDK4 activity is either inhibited or enhanced depending on stoichiometry of complex. The non-tyrosine-phosphorylated form of CDKN1B prevents T-loop phosphorylation of CDK4 producing inactive CDK4. Interacts (unphosphorylated form) with CDK2. Also forms ternary complexes with CDKN1A or CDKN2A. Interacts directly with CDKN1A (via its N-terminal); the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Interacts with CCND1; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression. Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (PubMed:29127155). Interacts with CEBPA (when phosphorylated) (PubMed:15107404). Interacts with FNIP1 and FNIP2 (PubMed:27353360).INTERACTION Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G(1) phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G(1) to S phase. Also present in nucleoli and heterochromatin lumps. Colocalizes with RB1 after release into the nucleus.ALTERNATIVE PRODUCTS Phosphorylation at Thr-172 is required for enzymatic activity. Phosphorylated, in vitro, at this site by CCNH-CDK7, but, in vivo, appears to be phosphorylated by a proline-directed kinase. In the cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 enzyme activity, is dependent on the tyrosine phosphorylation state of CDKN1B. Thus, in proliferating cells, CDK4 within the complex is phosphorylated on Thr-172 in the T-loop. In resting cells, phosphorylation on Thr-172 is prevented by the non-tyrosine-phosphorylated form of CDKN1B.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. |
| description | recommendedName: Cyclin-dependent kinase 4 ecNumber: 2.7.11.22 alternativeName: Cell division protein kinase 4 alternativeName: PSK-J3 |
| geneName | CDK4 |
| identifier | P11802 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing ATP-binding Cell cycle Cell division Cytoplasm Disease variant Kinase Membrane Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Transferase |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | CDK4 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8994117] ENSEMBL:ENSG00000135446 CDK4 [Homo sapiens] |
| secondaryIdentifier | CDK4_HUMAN B2R9A0 B4DNF9 O00576 Q6FG61 |
| sequenceLength | 303 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8966929] UniProt:P11802-1 CDK4 [Homo sapiens] [ReferenceIsoform:8966930] UniProt:P11802-2 CDK4 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:68330] CDK4 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:68344] p-T172-CDK4 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:113830] p-T172-CDK4 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:113843] CDK4 [nucleoplasm] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:68343] O4'-phospho-L-tyrosine at 649 [ModifiedResidue:113744] O-phospho-L-threonine at 172 |
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No pathways have been reviewed or authored by UniProt:P11802 CDK4 (68329)
