Recombinant Human Cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3 (CDKN2A)

Uniprot Id

P42771

Target Species

Human

Target Name

CDKN2A

Target Full Name

Cyclin-dependent kinase inhibitor 2A

Target 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.

Target Involvement

Melanoma, cutaneous malignant 2 (CMM2); Familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC); Melanoma-astrocytoma syndrome (MASTS)

Target Subcellular Location

Cytoplasm. Nucleus.

Target Protein Families

CDKN2 cyclin-dependent kinase inhibitor family

Target Tissue Specificity

Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific.

Target Synonyms

CDKN2A; CDKN2; MTS1; Cyclin-dependent kinase inhibitor 2A; Cyclin-dependent kinase 4 inhibitor A; CDK4I; Multiple tumor suppressor 1; MTS-1; p16-INK4a; p16-INK4; p16INK4A

Target Background

This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3 ubiquitin-protein ligase MDM2, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene.