Homo sapiens Gene: CDKN2A
Summary
InnateDB Gene IDBG-54547.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol CDKN2A
Gene Name cyclin-dependent kinase inhibitor 2A
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 Gene ENSG00000147889
Encoded Proteins
cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
The tumour suppressor CDKN2A plays a role in innate immunity as a regulator of inflammatory cell signalling. Cdkn2a null mice were unable to trigger a proper inflammatory response in experimental peritonitis or in induced edema and were resistant to LPS-induced endotoxic shock. (Demonstrated in mice)
Entrez Gene
Summary This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq, Sep 2012]
Gene Information
Type Protein coding
Genomic Location Chromosome 9:21967753-21995301
Strand Reverse strand
Band p21.3
Transcripts
ENST00000361570 ENSP00000355153
ENST00000304494 ENSP00000307101
ENST00000380151 ENSP00000369496
ENST00000380150
ENST00000498124 ENSP00000418915
ENST00000494262 ENSP00000464952
ENST00000479692 ENSP00000466887
ENST00000497750 ENSP00000468510
ENST00000498628 ENSP00000467857
ENST00000470819
ENST00000530628 ENSP00000432664
ENST00000579122 ENSP00000464202
ENST00000577854
ENST00000579755 ENSP00000462950
ENST00000578845 ENSP00000467390
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:0004861 cyclin-dependent protein serine/threonine kinase inhibitor activity
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0016301 kinase activity
GO:0019901 protein kinase binding
GO:0044822 poly(A) RNA binding
GO:0051059 NF-kappaB binding
GO:0055105 ubiquitin-protein transferase inhibitor activity
GO:0097371 MDM2/MDM4 family protein binding
Biological Process
GO:0000075 cell cycle checkpoint
GO:0000082 G1/S transition of mitotic cell cycle
GO:0000209 protein polyubiquitination
GO:0000278 mitotic cell cycle
GO:0001953 negative regulation of cell-matrix adhesion
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:0007265 Ras protein signal transduction
GO:0008285 negative regulation of cell proliferation
GO:0008637 apoptotic mitochondrial changes
GO:0010389 regulation of G2/M transition of mitotic cell cycle
GO:0016310 phosphorylation
GO:0030308 negative regulation of cell growth
GO:0030889 negative regulation of B cell proliferation
GO:0031647 regulation of protein stability
GO:0031648 protein destabilization
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0033088 negative regulation of immature T cell proliferation in thymus
GO:0033235 positive regulation of protein sumoylation
GO:0034393 positive regulation of smooth muscle cell apoptotic process
GO:0035986 senescence-associated heterochromatin focus assembly
GO:0042326 negative regulation of phosphorylation
GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator
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: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:0090399 replicative senescence
GO:1902510 regulation of apoptotic DNA fragmentation
GO:2000111 positive regulation of macrophage apoptotic process
GO:2000774 positive regulation of cellular senescence
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005829 cytosol
GO:0016604 nuclear body
GO:0035985 senescence-associated heterochromatin focus
GO:0043234 protein complex
Orthologs
No orthologs found for this gene
Pathways
NETPATH
REACTOME
G1 Phase pathway
Cellular responses to stress pathway
Oncogene Induced Senescence pathway
Mitotic G1-G1/S phases pathway
Cyclin D associated events in G1 pathway
Cell Cycle pathway
Cellular Senescence pathway
Cell Cycle, Mitotic pathway
Senescence-Associated Secretory Phenotype (SASP) pathway
Oxidative Stress Induced Senescence pathway
KEGG
Cell cycle pathway
p53 signaling pathway pathway
Pathways in cancer pathway
Pancreatic cancer pathway
Glioma pathway
Melanoma pathway
Bladder cancer pathway
Chronic myeloid leukemia pathway
Non-small cell lung cancer pathway
INOH
Hedgehog signaling pathway pathway
PID BIOCARTA
Cell cycle: g1/s check point [Biocarta view]
Ctcf: first multivalent nuclear factor [Biocarta view]
Tumor suppressor arf inhibits ribosomal biogenesis [Biocarta view]
Cyclins and cell cycle regulation [Biocarta view]
PID NCI
Validated transcriptional targets of AP1 family members Fra1 and Fra2
Regulation of retinoblastoma protein
Coregulation of Androgen receptor activity
p53 pathway
Regulation of nuclear beta catenin signaling and target gene transcription
AP-1 transcription factor network
C-MYB transcription factor network
E2F transcription factor network
C-MYC pathway
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha
Validated transcriptional targets of deltaNp63 isoforms
Validated transcriptional targets of TAp63 isoforms
FOXM1 transcription factor network
Cross-References
SwissProt
TrEMBL J3QRG6 Q9UPB7
UniProt Splice Variant
Entrez Gene 1029
UniGene Hs.661650
RefSeq NM_000077 NM_001195132 NM_058195 XM_005251343
HUGO HGNC:1787
OMIM 600160
CCDS CCDS56565 CCDS6510 CCDS6511
HPRD 02542
IMGT
EMBL AF044170 AL449423
GenPept AAD02319
RNA Seq Atlas 1029