ID:CD2A2_HUMAN DESCRIPTION: RecName: Full=Cyclin-dependent kinase inhibitor 2A, isoform 4; AltName: Full=p14ARF; AltName: Full=p19ARF; 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. 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. INTERACTION: Q9UER7:DAXX; NbExp=8; IntAct=EBI-625922, EBI-77321; Q8AZK7:EBNA-LP (xeno); NbExp=5; IntAct=EBI-625922, EBI-1185167; Q7Z6Z7:HUWE1; NbExp=4; IntAct=EBI-625922, EBI-625934; Q00987:MDM2; NbExp=3; IntAct=EBI-625922, EBI-389668; SUBCELLULAR LOCATION: Nucleus, nucleolus. Nucleus, nucleoplasm. 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. SEQUENCE CAUTION: Sequence=AAB01737.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAC60649.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAH15960.3; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAH21998.3; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=AAM77919.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=CAH70601.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=EAW58600.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; Sequence=EAW58601.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdkn2a/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q8N726
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Mouse
Rat
Zebrafish
D. melanogaster
C. elegans
S. cerevisiae
No ortholog
No ortholog
No ortholog
No ortholog
No ortholog
No ortholog
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0002039 p53 binding GO:0003677 DNA binding GO:0005515 protein binding GO:0008134 transcription factor binding GO:0019789 SUMO transferase activity GO:0055105 ubiquitin-protein transferase inhibitor activity GO:0097371 MDM2/MDM4 family protein binding GO:0097718 disordered domain specific binding GO:1990948 ubiquitin ligase inhibitor activity
Biological Process: GO:0000209 protein polyubiquitination GO:0000422 mitophagy GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006364 rRNA processing GO:0006469 negative regulation of protein kinase activity GO:0006915 apoptotic process GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0007049 cell cycle 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:0010628 positive regulation of gene expression GO:0016925 protein sumoylation 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:0043065 positive regulation of apoptotic process GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator 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:0051882 mitochondrial depolarization GO:0070534 protein K63-linked ubiquitination GO:0071158 positive regulation of cell cycle arrest GO:0090398 cellular senescence GO:1900182 positive regulation of protein localization to nucleus GO:1901798 positive regulation of signal transduction by p53 class mediator GO:1902510 regulation of apoptotic DNA fragmentation GO:1903051 negative regulation of proteolysis involved in cellular protein catabolic process GO:1903214 regulation of protein targeting to mitochondrion GO:1904667 negative regulation of ubiquitin protein ligase activity GO:1990000 amyloid fibril formation GO:2000059 negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:2000435 negative regulation of protein neddylation
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
