InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CDK4

Summary

InnateDB Protein

IDBP-43644.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CDK4

Protein Name

cyclin-dependent kinase 4

Synonyms

CMM3; PSK-J3;

Species

Homo sapiens

Ensembl Protein

ENSP00000257904

InnateDB Gene

IDBG-43642 (CDK4)

Protein Structure

UniProt Annotation

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:0000269PubMed:15241418, ECO:0000269PubMed:18827403, ECO:0000269PubMed:9003781}.

Subcellular Localization

Cytoplasm. Nucleus. Membrane. 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.

Disease Associations

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 also may involve other sites. {ECO:0000269PubMed:7652577, ECO:0000269PubMed:8528263, ECO:0000269PubMed:9311594, ECO:0000269PubMed:9425228}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 169 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.

Experimentally validated
Total	169 [view]
Protein-Protein	163 [view]
Protein-DNA	5 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	19 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004693	cyclin-dependent protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0030332	cyclin binding
GO:0032403	protein complex binding

Biological Process

GO:0000082	G1/S transition of mitotic cell cycle
GO:0000278	mitotic cell cycle
GO:0002088	lens development in camera-type eye
GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0007623	circadian rhythm
GO:0008284	positive regulation of cell proliferation
GO:0009636	response to toxic substance
GO:0010033	response to organic substance
GO:0010288	response to lead ion
GO:0010468	regulation of gene expression
GO:0010971	positive regulation of G2/M transition of mitotic cell cycle
GO:0031100	organ regeneration
GO:0033574	response to testosterone
GO:0042127	regulation of cell proliferation
GO:0042493	response to drug
GO:0043065	positive regulation of apoptotic process
GO:0045727	positive regulation of translation
GO:0045793	positive regulation of cell size
GO:0048146	positive regulation of fibroblast proliferation
GO:0051301	cell division
GO:0051726	regulation of cell cycle
GO:0055093	response to hyperoxia
GO:0071157	negative regulation of cell cycle arrest

Cellular Component

GO:0000307	cyclin-dependent protein kinase holoenzyme complex
GO:0000785	chromatin
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005667	transcription factor complex
GO:0005730	nucleolus
GO:0005829	cytosol
GO:0005923	tight junction
GO:0031965	nuclear membrane
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR002575 Aminoglycoside phosphotransferase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF01636

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt