PMEPA1

PMEPA1 is a transmembrane protein that contains a Smad interacting motif (SIM). Expression of this gene is induced by androgens and transforming growth factor beta, and the encoded protein suppresses the androgen receptor and transforming growth factor beta signaling pathways though interactions with Smad proteins.

Full Name

Prostate Transmembrane Protein, Androgen Induced 1

Function

Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal (PubMed:20129061, PubMed:24627487).
Also involved in down-regulation of the androgen receptor (AR), enhancing ubiquitination and proteasome-mediated degradation of AR, probably by recruiting NEDD4 (PubMed:18703514).

Biological Process

Androgen receptor signaling pathway1 PublicationNAS:UniProtKB
Negative regulation of pathway-restricted SMAD protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of SMAD protein complex assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of transforming growth factor beta receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Early endosome membrane
Golgi apparatus membrane

Topology

Lumenal: 1-40
Helical: 41-63
Cytoplasmic: 64-287