PMEPA1

Domain

The PPxY motifs mediate interaction with NEDD4.

The SMAD interaction motif is required for interaction with SMAD2 and SMAD3 and the negative regulation of TGF-beta signaling.

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).

Sequence similarities

Belongs to the PMEPA1 family.

Tissue specificity

Highest expression in prostate. Also expressed in ovary.

Cellular localization

• Early endosome membrane
• Single-pass membrane protein
• Golgi apparatus membrane
• Single-pass membrane protein

Alternative names

• Protein TMEPAI
• Prostate transmembrane protein androgen induced 1
• Solid tumor-associated 1 protein
• Transmembrane prostate androgen-induced protein
• TMEPAI
• PMEPA1
• STAG1

Database links

• entrezGene:56937
• omim:606564
• swissprot:Q969W9

Target type

Proteins

Molecular weight

31609Da