CDK4
entrez
1019
canonical
uniprot
P11802
canonical
ensembl
ENSG00000135446
resolver
ensp
ENSP00000257904
resolver
genesymbol
CDK4
resolver
hgnc
HGNC:1773
resolver
uniprot
B2R9A0
resolver
uniprot
B4DNF9
resolver
uniprot
O00576
resolver
uniprot
Q6FG61
resolver
uniprot_entry
CDK4_HUMAN
resolver
uniprot_sec
B2R9A0
resolver
uniprot_sec
B4DNF9
resolver
uniprot_sec
O00576
resolver
uniprot_sec
Q6FG61
resolver
activity_regulation
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. {ECO:0000269|PubMed:19487459}.
uniprot
proteins
amino_acid_sequence
MATSRYEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVPNGGGGGGGLPISTVREVALLRRLEAFEHPNVVRLMDVCATSRTDREIKVTLVFEHVDQDLRTYLDKAPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGTVKLADFGLARIYSYQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWPRDVSLPRGAFPPRGPRPVQSVVPEMEESGAQLLLEMLTFNPHKRISAFRALQHSYLHKDEGNPE
uniprot
proteins
disease_involvement
DISEASE: Melanoma, cutaneous malignant 3 (CMM3) [MIM:609048]: A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites. {ECO:0000269|PubMed:7652577, ECO:0000269|PubMed:8528263, ECO:0000269|PubMed:9311594, ECO:0000269|PubMed:9425228}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Microcephaly 31, primary, autosomal recessive (MCPH31) [MIM:621507]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH31 is characterized by progressive small head circumference, poor overall postnatal growth and short stature. Learning disabilities or speech delay may be present. {ECO:0000269|PubMed:40210435}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.22
uniprot
proteins
function
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. {ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:9003781}.
uniprot
proteins
mass_dalton
33730
uniprot
proteins
mutagenesis
MUTAGEN 172; /note="T->A: Weak enzyme activity towards RB1, but no effect on binding of CCDN1 nor CCDN3."; /evidence="ECO:0000269|PubMed:16782892"; MUTAGEN 172; /note="T->E: Retains moderate enzyme activity."; /evidence="ECO:0000269|PubMed:16782892"; MUTAGEN 173; /note="P->S: No effect on in vitro phosphorylation by CDK7. Greatly reduced T-172 phosphorylation and enzyme activity."; /evidence="ECO:0000269|PubMed:19487459
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:19075005, ECO:0000269|PubMed:19237555, ECO:0000269|PubMed:19237565, ECO:0000269|PubMed:19487459}.
uniprot
proteins
protein_family
CDC2/CDKX subfamily
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10580009
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15107404
uniprot
proteins
pubmed
15241418
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15558030
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
16782892
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18827403
uniprot
proteins
pubmed
19075005
uniprot
proteins
pubmed
19124461
uniprot
proteins
pubmed
19237555
uniprot
proteins
pubmed
19237565
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19487459
uniprot
proteins
pubmed
20399237
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
27353360
uniprot
proteins
pubmed
29127155
uniprot
proteins
pubmed
2948189
uniprot
proteins
pubmed
40210435
uniprot
proteins
pubmed
7652577
uniprot
proteins
pubmed
8221695
uniprot
proteins
pubmed
8528263
uniprot
proteins
pubmed
9003781
uniprot
proteins
pubmed
9106657
uniprot
proteins
pubmed
9192850
uniprot
proteins
pubmed
9311594
uniprot
proteins
pubmed
9425228
uniprot
proteins
sequence_length
303
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18827403}. Nucleus {ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:20399237, ECO:0000269|PubMed:9106657}. Nucleus membrane {ECO:0000269|PubMed:18827403}. Note=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. {ECO:0000269|PubMed:18827403}.
uniprot
proteins