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MT000115

UniProt Annotations

Entry Information

Gene Name	cyclin-dependent kinase inhibitor 2A
Protein Entry	CD2A2_HUMAN
UniProt ID	Q8N726
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=6; Comment=Isoform 1 and isoform 4 arise due to the use of two alternative first exons joined to a common exon 2 at the same acceptor site but in different reading frames, resulting in two completely different isoforms. {ECO:0000250\|UniProtKB:Q64364}; Name=4 {ECO:0000269\|PubMed:7606716}; Synonyms=p14ARF {ECO:0000303\|PubMed:9724636}, p19ARF, ARF {ECO:0000303\|PubMed:11314011}; IsoId=Q8N726-1; Sequence=Displayed; Name=1 {ECO:0000305}; Synonyms=p16INK4a {ECO:0000305}; IsoId=P42771-1; Sequence=External; Name=2 {ECO:0000305}; IsoId=P42771-2; Sequence=External; Name=3 {ECO:0000305}; Synonyms=p12 {ECO:0000305}; IsoId=P42771-3; Sequence=External; Name=5; Synonyms=p16gamma; IsoId=P42771-4; Sequence=External; Note=Barely detectable in non-tumor cells.; Name=6; Synonyms=smARF; IsoId=Q8N726-2; Sequence=VSP_044962;
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:0000269\|PubMed:11314011, ECO:0000269\|PubMed:11314038, ECO:0000269\|PubMed:12660818, ECO:0000269\|PubMed:14636574, ECO:0000269\|PubMed:15361825, ECO:0000269\|PubMed:15567177, ECO:0000269\|PubMed:15876874, ECO:0000269\|PubMed:15989956, ECO:0000269\|PubMed:18305112, ECO:0000269\|PubMed:9724636}.
Interaction	Q07021:C1QBP; NbExp=3; IntAct=EBI-625922, EBI-347528; Q9UER7:DAXX; NbExp=8; IntAct=EBI-625922, EBI-77321; Q8AZK7:EBNA-LP (xeno); NbExp=5; IntAct=EBI-625922, EBI-1185167; P18146:EGR1; NbExp=4; IntAct=EBI-625922, EBI-2834611; Q7Z6Z7:HUWE1; NbExp=4; IntAct=EBI-625922, EBI-625934; Q00987:MDM2; NbExp=5; IntAct=EBI-625922, EBI-389668; P04198:MYCN; NbExp=3; IntAct=EBI-625922, EBI-878369; P06748:NPM1; NbExp=2; IntAct=EBI-625922, EBI-78579; Q8TAQ5:ZNF420; NbExp=8; IntAct=EBI-625922, EBI-3923307;
Ptm	Ubiquitinated in normal cells by TRIP12 via the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination at the N-terminus, regardeless of the absence of lysine residues. Ubiquitination leads to its degradation. In cancer cells, however, TRIP12 is located in a different cell compartment, preventing ubiquitination and degradation. {ECO:0000269\|PubMed:20208519}.
Sequence Caution	Sequence=AAB01737.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=AAC60649.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=AAH15960.3; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=AAH21998.3; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=AAM77919.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=CAH70601.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=EAW58600.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=EAW58601.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
Subcellular Location	Isoform 6: Mitochondrion {ECO:0000269\|PubMed:16713577}.
Subcellular Location	Nucleus, nucleolus {ECO:0000269\|PubMed:18305112}. Nucleus, nucleoplasm {ECO:0000269\|PubMed:18305112}.
Subunit	Does not interact with cyclins, CDK1, CDK2, CDK4, CDK5 or CDK6. Binds to BCL6, E2F1, HUWE1, MDM2, MYC, NPM1/B23, TOP1/TOPOI and UBE2I/UBC9. Interacts with TBRG1 and COMMD1. Interacts with CDKN2AIP and E4F1. Isoform 6 interacts with C1QBP. {ECO:0000269\|PubMed:11314011, ECO:0000269\|PubMed:11314038, ECO:0000269\|PubMed:12154087, ECO:0000269\|PubMed:12446718, ECO:0000269\|PubMed:12581788, ECO:0000269\|PubMed:14636574, ECO:0000269\|PubMed:15361825, ECO:0000269\|PubMed:15567177, ECO:0000269\|PubMed:15876874, ECO:0000269\|PubMed:15989956, ECO:0000269\|PubMed:17110379, ECO:0000269\|PubMed:17486078, ECO:0000269\|PubMed:18305112, ECO:0000269\|PubMed:9724636}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CDKN2aID146.html";
Web Resource	Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdkn2a/";