InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CDKN2A

Summary

InnateDB Protein

IDBP-479083.4

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

ENSP00000418915

InnateDB Gene

IDBG-54547 (CDKN2A)

Protein Structure

UniProt Annotation

Function

Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein. {ECO:0000269PubMed:16782892, ECO:0000269PubMed:7972006}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:17658461}. Nucleus {ECO:0000269PubMed:17658461}.

Disease Associations

Note=The association between cutaneous and uveal melanomas in some families suggests that mutations in CDKN2A may account for a proportion of uveal melanomas. However, CDKN2A mutations are rarely found in uveal melanoma patients.Melanoma, cutaneous malignant 2 (CMM2) [MIM:155601]: 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:10651484, ECO:0000269PubMed:10874641, ECO:0000269PubMed:11506491, ECO:0000269PubMed:12019208, ECO:0000269PubMed:14646619, ECO:0000269PubMed:19260062, ECO:0000269PubMed:7987387, ECO:0000269PubMed:8595405, ECO:0000269PubMed:8653684, ECO:0000269PubMed:8710906, ECO:0000269PubMed:9328469, ECO:0000269PubMed:9425228}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC) [MIM:606719]: An inherited cancer predisposition syndrome characterized by an increased risk of developing malignant melanoma and/or pancreatic cancer. Mutation carriers within families may develop either or both types of cancer. Note=The disease is caused by mutations affecting the gene represented in this entry.Li-Fraumeni syndrome (LFS) [MIM:151623]: Autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers. {ECO:0000269PubMed:10484981}. Note=The disease is caused by mutations affecting the gene represented in this entry.Melanoma-astrocytoma syndrome (MASTS) [MIM:155755]: Characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma. {ECO:0000269PubMed:11136714}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific. {ECO:0000269PubMed:10445844}.

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:0004861	cyclin-dependent protein serine/threonine kinase inhibitor activity
GO:0005515	protein binding
GO:0019901	protein kinase binding
GO:0044822	poly(A) RNA binding
GO:0051059	NF-kappaB binding

Biological Process

GO:0000075	cell cycle checkpoint
GO:0000082	G1/S transition of mitotic cell cycle
GO:0000278	mitotic cell cycle
GO:0001953	negative regulation of cell-matrix adhesion
GO:0007050	cell cycle arrest
GO:0007265	Ras protein signal transduction
GO:0008285	negative regulation of cell proliferation
GO:0030308	negative regulation of cell growth
GO:0032088	negative regulation of NF-kappaB transcription factor activity
GO:0034393	positive regulation of smooth muscle cell apoptotic process
GO:0035986	senescence-associated heterochromatin focus assembly
GO:0042326	negative regulation of phosphorylation
GO:0045087	innate immune response (InnateDB)
GO:0045736	negative regulation of cyclin-dependent protein serine/threonine kinase activity
GO:0045892	negative regulation of transcription, DNA-templated
GO:0090399	replicative senescence
GO:2000111	positive regulation of macrophage apoptotic process
GO:2000774	positive regulation of cellular senescence