PRAME

PRAME is an antigen that is preferentially expressed in human melanomas and that is recognized by cytolytic T lymphocytes. It is not expressed in normal tissues, except testis. The encoded protein acts as a repressor of retinoic acid receptor, and likely confers a growth advantage to cancer cells via this function.

Full Name

Preferentially Expressed Antigen In Melanoma

Function

Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex, which mediates ubiquitination of target proteins, leading to their degradation (PubMed:21822215, PubMed:26138980).
The CRL2(PRAME) complex mediates ubiquitination and degradation of truncated MSRB1/SEPX1 selenoproteins produced by failed UGA/Sec decoding (PubMed:26138980).
In the nucleus, the CRL2(PRAME) complex is recruited to epigenetically and transcriptionally active promoter regions bound by nuclear transcription factor Y (NFY) and probably plays a role in chromstin regulation (PubMed:21822215).
Functions as a transcriptional repressor, inhibiting the signaling of retinoic acid through the retinoic acid receptors RARA, RARB and RARG: prevents retinoic acid-induced cell proliferation arrest, differentiation and apoptosis (PubMed:16179254).

Biological Process

Apoptotic processIEA:UniProtKB-KW
Cell differentiationIEA:UniProtKB-KW
Negative regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of cell differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of retinoic acid receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIDA:UniProtKB
Proteasome-mediated ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Protein polyubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of growthIEA:UniProtKB-KW

Cellular Location

Nucleus
Chromosome
Cytoplasm
Golgi apparatus
Cell membrane
Associates with chromatin; specifically enriched at transcriptionally active promoters that are also bound by nuclear transcription factor Y (composed of NFYA, NFYB and NFYC) and at enhancers (PubMed:21822215).
Recruited to the Golgi apparatus in response to interferon gamma (IFNG) treatment (PubMed:23460923).