UniProt functional annotation for P42771



	UniProt functional annotation for P42771

UniProt code: P42771.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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:0000269|PubMed:16782892, ECO:0000269|PubMed:7972006}.

Subunit: Heterodimer with CDK4 or CDK6. Predominant p16 complexes contained CDK6. Interacts with CDK4 (both 'T-172'-phosphorylated and non-phosphorylated forms); the interaction inhibits cyclin D-CDK4 kinase activity. Interacts with ISCO2. {ECO:0000269|PubMed:16782892, ECO:0000269|PubMed:17658461}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:17658461}. Nucleus {ECO:0000269|PubMed:17658461}.

Tissue specificity: Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific. {ECO:0000269|PubMed:10445844}.

Ptm: Phosphorylation seems to increase interaction with CDK4. {ECO:0000269|PubMed:12529334}.

Disease: 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.

Disease: 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:0000269|PubMed:10651484, ECO:0000269|PubMed:10874641, ECO:0000269|PubMed:11506491, ECO:0000269|PubMed:12019208, ECO:0000269|PubMed:14646619, ECO:0000269|PubMed:19260062, ECO:0000269|PubMed:7987387, ECO:0000269|PubMed:8595405, ECO:0000269|PubMed:8653684, ECO:0000269|PubMed:8710906, ECO:0000269|PubMed:9328469, ECO:0000269|PubMed:9425228}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Disease: 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 variants affecting the gene represented in this entry.

Disease: Melanoma-astrocytoma syndrome (MASTS) [MIM:155755]: Characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma. {ECO:0000269|PubMed:11136714}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform 5]: Barely detectable in non-tumor cells. {ECO:0000305}.

Similarity: Belongs to the CDKN2 cyclin-dependent kinase inhibitor family. {ECO:0000305}.

Sequence caution: Sequence=AAB60645.1; Type=Erroneous initiation; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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:0000269\|PubMed:16782892, ECO:0000269\|PubMed:7972006}.


Subunit:		Heterodimer with CDK4 or CDK6. Predominant p16 complexes contained CDK6. Interacts with CDK4 (both 'T-172'-phosphorylated and non-phosphorylated forms); the interaction inhibits cyclin D-CDK4 kinase activity. Interacts with ISCO2. {ECO:0000269\|PubMed:16782892, ECO:0000269\|PubMed:17658461}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:17658461}. Nucleus {ECO:0000269\|PubMed:17658461}.
Tissue specificity:		Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific. {ECO:0000269\|PubMed:10445844}.
Ptm:		Phosphorylation seems to increase interaction with CDK4. {ECO:0000269\|PubMed:12529334}.
Disease:		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.
Disease:		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:0000269\|PubMed:10651484, ECO:0000269\|PubMed:10874641, ECO:0000269\|PubMed:11506491, ECO:0000269\|PubMed:12019208, ECO:0000269\|PubMed:14646619, ECO:0000269\|PubMed:19260062, ECO:0000269\|PubMed:7987387, ECO:0000269\|PubMed:8595405, ECO:0000269\|PubMed:8653684, ECO:0000269\|PubMed:8710906, ECO:0000269\|PubMed:9328469, ECO:0000269\|PubMed:9425228}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Disease:		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 variants affecting the gene represented in this entry.
Disease:		Melanoma-astrocytoma syndrome (MASTS) [MIM:155755]: Characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma. {ECO:0000269\|PubMed:11136714}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform 5]: Barely detectable in non-tumor cells. {ECO:0000305}.
Similarity:		Belongs to the CDKN2 cyclin-dependent kinase inhibitor family. {ECO:0000305}.
Sequence caution:		Sequence=AAB60645.1; Type=Erroneous initiation; Evidence={ECO:0000305};