InnateDB Protein
|
IDBP-54551.6
|
Last Modified
|
2014-10-13 [Report errors or provide feedback]
|
Gene Symbol
|
CDKN2A
|
Protein Name
|
cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
|
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 Protein
|
ENSP00000307101
|
InnateDB Gene
|
IDBG-54547 (CDKN2A)
|
Protein Structure
|
|
Function |
Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein. {ECO:0000269PubMed:16782892, ECO:0000269PubMed:7972006}.
|
Subcellular Localization |
Cytoplasm {ECO:0000269PubMed:17658461}. Nucleus {ECO:0000269PubMed:17658461}.
|
Disease Associations |
Note=The association between cutaneous and uveal melanomas in some families suggests that mutations in CDKN2A may account for a proportion of uveal melanomas. However, CDKN2A mutations are rarely found in uveal melanoma patients.Melanoma, cutaneous malignant 2 (CMM2) [MIM:155601]: A malignant neoplasm of melanocytes, arising de novo or from a pre- existing benign nevus, which occurs most often in the skin but also may involve other sites. {ECO:0000269PubMed:10651484, ECO:0000269PubMed:10874641, ECO:0000269PubMed:11506491, ECO:0000269PubMed:12019208, ECO:0000269PubMed:14646619, ECO:0000269PubMed:19260062, ECO:0000269PubMed:7987387, ECO:0000269PubMed:8595405, ECO:0000269PubMed:8653684, ECO:0000269PubMed:8710906, ECO:0000269PubMed:9328469, ECO:0000269PubMed:9425228}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC) [MIM:606719]: An inherited cancer predisposition syndrome characterized by an increased risk of developing malignant melanoma and/or pancreatic cancer. Mutation carriers within families may develop either or both types of cancer. Note=The disease is caused by mutations affecting the gene represented in this entry.Li-Fraumeni syndrome (LFS) [MIM:151623]: Autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers. {ECO:0000269PubMed:10484981}. Note=The disease is caused by mutations affecting the gene represented in this entry.Melanoma-astrocytoma syndrome (MASTS) [MIM:155755]: Characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma. {ECO:0000269PubMed:11136714}. Note=The disease is caused by mutations affecting the gene represented in this entry.
|
Tissue Specificity |
Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific. {ECO:0000269PubMed:10445844}.
|
Comments |
|
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
|
|
|
|
Molecular Function |
|
Biological Process |
GO:0000075
|
cell cycle checkpoint
|
GO:0000082
|
G1/S transition of mitotic cell cycle
|
GO:0000278
|
mitotic cell cycle
|
GO:0001953
|
negative regulation of cell-matrix adhesion
|
GO:0007050
|
cell cycle arrest
|
GO:0007265
|
Ras protein signal transduction
|
GO:0008285
|
negative regulation of cell proliferation
|
GO:0030308
|
negative regulation of cell growth
|
GO:0032088
|
negative regulation of NF-kappaB transcription factor activity
|
GO:0034393
|
positive regulation of smooth muscle cell apoptotic process
|
GO:0035986
|
senescence-associated heterochromatin focus assembly
|
GO:0042326
|
negative regulation of phosphorylation
|
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:0090399
|
replicative senescence
|
GO:2000111
|
positive regulation of macrophage apoptotic process
|
GO:2000774
|
positive regulation of cellular senescence
|
|
Cellular Component |
|
PDB ID |
|
InterPro |
IPR020683
Ankyrin repeat-containing domain
|
PFAM |
PF11929
PF12796
|
PRINTS |
|
PIRSF |
|
SMART |
|
TIGRFAMs |
|
Modification |
|
SwissProt |
P42771
|
PhosphoSite |
PhosphoSite-P42771
|
TrEMBL |
Q9UPB7
|
UniProt Splice Variant |
|
Entrez Gene |
1029
|
UniGene |
Hs.661650
|
RefSeq |
NP_000068
|
HUGO |
HGNC:1787
|
OMIM |
600160
|
CCDS |
CCDS6510
|
HPRD |
02542
|
IMGT |
|
EMBL |
AB060808
AF044170
AF115544
AF527803
AH007355
AL449423
CH471071
DQ318021
JQ694043
JQ694044
JQ694045
L27211
S69804
U12818
U12819
U12820
X94154
|
GenPept |
AAA92554
AAB60645
AAD02319
AAD11437
AAD14048
AAD14050
AAR05391
ABC47036
AFN61598
AFN61599
AFN61600
BAB91133
CAA63870
CAH70600
EAW58599
EAW58603
|
|
|