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Protein Page:
p16-INK4A (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
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: 9p21
Cellular Component: cytoplasm; cytosol; mitochondrion; nuclear body; nucleolus; nucleoplasm; nucleus; protein complex
Molecular Function: cyclin-dependent protein kinase inhibitor activity; DNA binding; NF-kappaB binding; p53 binding; protein binding; protein kinase binding; transcription factor binding; ubiquitin-protein ligase inhibitor activity
Biological Process: apoptotic mitochondrial changes; caspase activation; cell cycle arrest; cellular protein metabolic process; G1/S transition of mitotic cell cycle; inhibition of NF-kappaB transcription factor; mitochondrial depolarization; mitochondrion degradation; mitotic cell cycle; negative regulation of B cell proliferation; negative regulation of cell growth; negative regulation of cell proliferation; negative regulation of cell-matrix adhesion; negative regulation of cyclin-dependent protein kinase activity; negative regulation of immature T cell proliferation in the thymus; negative regulation of phosphorylation; negative regulation of protein kinase activity; negative regulation of transcription, DNA-dependent; negative regulation of ubiquitin-protein ligase activity; positive regulation of apoptosis; positive regulation of DNA damage response, signal transduction by p53 class mediator; positive regulation of protein sumoylation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; post-translational protein modification; protein destabilization; protein polyubiquitination; protein stabilization; protein sumoylation; Ras protein signal transduction; regulation of G2/M transition of mitotic cell cycle; regulation of protein export from nucleus; regulation of protein stability; rRNA processing; somatic stem cell division; transcription, DNA-dependent
Disease: Melanoma, Cutaneous Malignant, Susceptibility To, 2; Melanoma-astrocytoma Syndrome; Melanoma-pancreatic Cancer Syndrome
Reference #:  P42771 (UniProtKB)
Alt. Names/Synonyms: ARF; CD2A1; CDK4 inhibitor p16-INK4; CDK4I; CDKN2; CDKN2A; cell cycle negative regulator beta; CMM2; Cyclin-dependent kinase 4 inhibitor A; cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4); cyclin-dependent kinase inhibitor 2A, isoform 4; Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3; cyclin-dependent kinase inhibitor p16; INK4; INK4a; MLM; MTS-1; MTS1; Multiple tumor suppressor 1; p14; p14ARF; p16; p16-INK4; p16-INK4a; p16INK4; p16INK4A; p19; p19Arf; TP16
Gene Symbols: CDKN2A
Molecular weight: 16,533 Da
Basal Isoelectric point: 5.52  Predict pI for various phosphorylation states
CST Pathways:  G1/S Checkpoint
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

p16-INK4A

Protein Structure Not Found.


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Sites Implicated In
activity, inhibited: S8‑p
molecular association, regulation: S140‑p, S152‑p
protein stabilization: S7‑p, S8‑p, S140‑p, S152‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 LTP 

LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 HTP 

HTP: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
3 0 S7‑p _MEPAAGssMEPSAD
3 0 S8‑p MEPAAGssMEPSADW
0 1 Y44‑p LPNAPNSyGRRPIQV
2 0 - gap
0 5 - gap
0 2 - gap
0 1 - gap
0 4 - gap
1 0 - gap
0 1 - gap
0 1 - gap
3 0 S140‑p AAGGTRGsNHARIDA
3 1 S152‑p IDAAEGPsDIPD___
0 1 - gap
0 1 - gap
0 1 - gap
  p16-INK4A iso2  
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
S26 HDDGQRPSGGAAAAP
C53 HPTRARRCPGGLPGH
- gap
- gap
- gap
- gap
- gap
- gap
  p16-INK4A iso3  
S7 _MEPAAGSSMEPSAD
S8 MEPAAGSSMEPSADW
Y44 LPNAPNSYGRRPIQV
- gap
- gap
- gap
S76‑p KFAGELEsGsASILR
S78‑p AGELEsGsASILRKK
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
  p16-INK4A iso4  
- gap
- gap
- gap
T8‑p MVRRFLVtLRIRRAC
H26 RVRVFVVHIPRLtGE
T31‑p VVHIPRLtGEWAAPG
- gap
- gap
S73 HDDGQRPSGGAAAAP
C100 HPTRARRCPGGLPGH
- gap
- gap
- gap
- gap
- gap
- gap
  mouse

► Hide Isoforms
 
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
- gap
S164‑p ALELRGQsQEQs___
S168‑p RGQsQEQs_______
- gap
  p16-INK4A iso3  
- gap
- gap
- gap
T8 MGRRFLVTVRIQRAG
K26‑ub QERVFLVkFVRSRRP
R31 LVkFVRSRRPRTASC
- gap
- gap
S71‑p GDDDGQRsRSSSSAQ
S99‑p LPPGARRsAGRLPGH
S125‑p GCARCLGsPAARLGP
- gap
- gap
- gap
- gap
Y159‑p FRWVVFVyRWERRPD
  rat

 
- gap
- gap
- gap
T8 MGRRFVVTVRIRRTG
Q26 QVRVFLVQFLGSsRP
S31‑p LVQFLGSsRPRSANG
- gap
- gap
S72 DDDGQRQSGSSPALL
S99 LPTGARRSAGGLPRH
S125 GCARCLGSPAARPGP
- gap
- gap
- gap
- gap
- gap
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