p16-INK4A a cell-cycle regulatory protein that interacts with CDK4 and CDK6, inhibiting their ability to interact with cyclins D. Inhibits the phosphorylation of the retinoblastoma protein by CDK4 or CDK6, and entry into the S phase of the cell cycle. The p16INK4A and p14ARF proteins are encoded by CDKN2A, a known tumour suppressor gene in multiple cancers. CDKN2A is inactivated in 72% of cases of lung squamous cell carcinoma: 21% by epigenetic silencing by methylation, 18% inactivating mutation, 4% by exon 1b skipping, and 29% by homozygous deletion. Defects in CDKN2A are the cause of familial atypical multiple mole melanoma-pancreatic carcinoma syndrome, Li-Fraumeni syndrome, and the melanoma-astrocytoma syndrome. The melanoma-astrocytoma syndrome is characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma. Four alternatively spliced p16 isoforms have been reported. Two alternatively spliced isoforms of ARF have been reported. Note: This description may include information from UniProtKB.
Protein type: Cell cycle regulation; Nucleolus; Tumor suppressor
Chromosomal Location of Human Ortholog: 4 C4|4 42.15 cM
Cellular Component:  cytoplasm; granular component; mitochondrion; nucleolus; nucleoplasm; nucleus; protein-containing complex; senescence-associated heterochromatin focus
Molecular Function:  cyclin-dependent protein serine/threonine kinase inhibitor activity; disordered domain specific binding; DNA binding; DNA-binding transcription factor activity; MDM2/MDM4 family protein binding; NF-kappaB binding; p53 binding; protein binding; protein kinase binding; protein N-terminus binding; SUMO transferase activity; transcription factor binding; ubiquitin ligase inhibitor activity; ubiquitin-protein transferase inhibitor activity
Biological Process:  activation of cysteine-type endopeptidase activity involved in apoptotic process; aging; amyloid fibril formation; apoptotic mitochondrial changes; apoptotic process; autophagy of mitochondrion; cell aging; cell cycle; cell cycle arrest; cellular response to hydrogen peroxide; cellular senescence; epidermis development; G1/S transition of mitotic cell cycle; glucose homeostasis; mitochondrial depolarization; negative regulation of B cell proliferation; negative regulation of cell cycle; negative regulation of cell growth; negative regulation of cell proliferation; negative regulation of cell-matrix adhesion; negative regulation of cyclin-dependent protein serine/threonine kinase activity; negative regulation of hepatocyte proliferation; negative regulation of immature T cell proliferation in thymus; negative regulation of mammary gland epithelial cell proliferation; negative regulation of NF-kappaB transcription factor activity; negative regulation of phosphorylation; negative regulation of protein binding; negative regulation of protein kinase activity; negative regulation of protein neddylation; negative regulation of proteolysis involved in cellular protein catabolic process; negative regulation of transcription, DNA-templated; negative regulation of ubiquitin protein ligase activity; negative regulation of ubiquitin-dependent protein catabolic process; negative regulation of ubiquitin-protein transferase activity; positive regulation of apoptotic process; positive regulation of apoptotic process involved in mammary gland involution; positive regulation of cell cycle arrest; positive regulation of cellular senescence; positive regulation of DNA damage response, signal transduction by p53 class mediator; positive regulation of DNA-binding transcription factor activity; positive regulation of gene expression; positive regulation of macrophage apoptotic process; positive regulation of protein localization to nucleus; positive regulation of protein sumoylation; positive regulation of signal transduction by p53 class mediator; positive regulation of smooth muscle cell apoptotic process; positive regulation of transcription by RNA polymerase II; positive regulation of transcription, DNA-templated; protein destabilization; protein K63-linked ubiquitination; protein polyubiquitination; protein stabilization; regulation of apoptotic DNA fragmentation; regulation of cyclin-dependent protein serine/threonine kinase activity; regulation of G2/M transition of mitotic cell cycle; regulation of gene expression; regulation of nucleocytoplasmic transport; regulation of protein export from nucleus; regulation of protein stability; regulation of protein targeting to mitochondrion; regulation of transcription, DNA-templated; replicative senescence; response to drug; response to organic cyclic compound; response to organonitrogen compound; rRNA processing; rRNA transcription; senescence-associated heterochromatin focus assembly; somatic stem cell division; somatic stem cell population maintenance
Reference #:  P51480 (UniProtKB)
Alt. Names/Synonyms: Arf; ARF-INK4a; CD2A1; CDK4I; Cdkn2a; Cyclin-dependent kinase 4 inhibitor A; Cyclin-dependent kinase inhibitor 2A; cyclin-dependent kinase inhibitor 2A (p16, inhibits CDK4); cyclin-dependent kinase inhibitor 2A, isoform 3; Cyclin-dependent kinase inhibitor 2A, isoforms 1/2; cyclin-dependent kinase inhibitor protein; INK4a-ARF; Ink4a/Arf; mitochondrial smARF; MTS1; OTTMUSP00000008143; p16; p16(INK4a); p16-INK4; p16-INK4a; P16ink4a; p19<ARF>; p19ARF; Pctr1
Gene Symbols: Cdkn2a
Molecular weight: 17,941 Da
Basal Isoelectric point: 6.04  Predict pI for various phosphorylation states
CST Pathways:  G1/S Checkpoint
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene