InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CDKN2A

Summary

InnateDB Protein

IDBP-54549.6

Last Modified

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

Gene Symbol

CDKN2A

Protein Name

cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)

Synonyms

ARF; CDK4I; CDKN2; CMM2; INK4; INK4A; MLM; MTS-1; MTS1; P14; P14ARF; P16; P16-INK4A; P16INK4; P16INK4A; P19; P19ARF; TP16;

Species

Homo sapiens

Ensembl Protein

ENSP00000355153

InnateDB Gene

IDBG-54547 (CDKN2A)

Protein Structure

UniProt Annotation

Function

Capable of inducing cell cycle arrest in G1 and G2 phases. Acts as a tumor suppressor. Binds to MDM2 and blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits the oncogenic action of MDM2 by blocking MDM2- induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis. Also induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2 complexes. Binds to BCL6 and down-regulates BCL6-induced transcriptional repression. Binds to E2F1 and MYC and blocks their transcriptional activator activity but has no effect on MYC transcriptional repression. Binds to TOP1/TOPOI and stimulates its activity. This complex binds to rRNA gene promoters and may play a role in rRNA transcription and/or maturation. Interacts with NPM1/B23 and promotes its polyubiquitination and degradation, thus inhibiting rRNA processing. Interacts with COMMD1 and promotes its 'Lys63'-linked polyubiquitination. Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its binding partners including MDM2 and E2F1. Binds to HUWE1 and represses its ubiquitin ligase activity. May play a role in controlling cell proliferation and apoptosis during mammary gland development. Isoform 6 may be involved in regulation of autophagy and caspase-independent cell death; the short-lived mitochondrial isoform is stabilized by C1QBP. {ECO:0000269PubMed:11314011, ECO:0000269PubMed:11314038, ECO:0000269PubMed:12660818, ECO:0000269PubMed:14636574, ECO:0000269PubMed:15361825, ECO:0000269PubMed:15567177, ECO:0000269PubMed:15876874, ECO:0000269PubMed:15989956, ECO:0000269PubMed:18305112, ECO:0000269PubMed:9724636}.

Subcellular Localization

Nucleus, nucleolus {ECO:0000269PubMed:18305112}. Nucleus, nucleoplasm {ECO:0000269PubMed:18305112}.Isoform 6: Mitochondrion {ECO:0000269PubMed:16713577}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 200 experimentally validated interaction(s) in this database.

Experimentally validated
Total	200 [view]
Protein-Protein	195 [view]
Protein-DNA	5 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002039	p53 binding
GO:0003677	DNA binding
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0055105	ubiquitin-protein transferase inhibitor activity
GO:0097371	MDM2/MDM4 family protein binding

Biological Process

GO:0000209	protein polyubiquitination
GO:0006351	transcription, DNA-templated
GO:0006364	rRNA processing
GO:0006469	negative regulation of protein kinase activity
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007050	cell cycle arrest
GO:0008285	negative regulation of cell proliferation
GO:0008637	apoptotic mitochondrial changes
GO:0010389	regulation of G2/M transition of mitotic cell cycle
GO:0030889	negative regulation of B cell proliferation
GO:0031647	regulation of protein stability
GO:0031648	protein destabilization
GO:0033088	negative regulation of immature T cell proliferation in thymus
GO:0033235	positive regulation of protein sumoylation
GO:0043517	positive regulation of DNA damage response, signal transduction by p53 class mediator
GO:0045087	innate immune response (InnateDB)
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046825	regulation of protein export from nucleus
GO:0048103	somatic stem cell division
GO:0050821	protein stabilization
GO:0051444	negative regulation of ubiquitin-protein transferase activity
GO:0070534	protein K63-linked ubiquitination
GO:0071158	positive regulation of cell cycle arrest
GO:0090398	cellular senescence
GO:1902510	regulation of apoptotic DNA fragmentation