PMEPA_HUMAN » Transmembrane prostate androgen-induced protein

PMEPA_HUMAN » Transmembrane prostate androgen-induced protein
Magnify PMEPA_HUMAN » Transmembrane prostate androgen-induced proteinEnlarged view of image
3D view in GLMol or JMol

gray dot

Download Coordinates

gray dot

Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
PMEPA_HUMAN » Transmembrane prostate androgen-induced protein » Solid tumor-associated 1 protein;
Hydrophobic Thickness 39.6 ± 1.6 Å
Tilt Angle 3 ± 2°
ΔGtransfer -54.3 kcal/mol
ΔGfold -29.0 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 38-62 (38-70)
Pathways

Signal Transduction (Reactome)

PDB none
OPM none
Complexes none
Interactions none
Domains none
UniProt annotation for PMEPA_HUMAN » Transmembrane prostate androgen-induced protein
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, PubMed). Also involved in down-regulation of the androgen receptor (AR), enhancing ubiquitination and proteasome-mediated degradation of AR, probably by recruiting NEDD4 (PubMed).

SUBUNIT: Interacts with NEDD4 (WW-binding motifs). Interacts with AR. Interacts with LDLRAD4. Interacts (via the SMAD interaction motif) with SMAD2 and SMAD3.

TISSUE SPECIFICITY: Highest expression in prostate. Also expressed in ovary.

INDUCTION: Up-regulated by androgen and TGF-beta (at protein level).

DOMAIN: The WW-binding motifs mediate interaction with NEDD4.

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

UniProt features for PMEPA_HUMAN » Transmembrane prostate androgen-induced protein
CHAIN 1 287 Transmembrane prostate androgen-induced protein.
MOTIF 158 161 WW-binding 1.
MOTIF 229 232 WW-binding 2.
Amino Acid Sequence for PMEPA_HUMAN » Transmembrane prostate androgen-induced protein
MHRLMGVNST AAAAAGQPNV SCTCNCKRSL FQSMEITELE FVQIIIIVVV MMVMVVVITC LLSHYKLSAR SFISRHSQGR RREDALSSEG CLWPSESTVS GNGIPEPQVY APPRPTDRLA VPPFAQRERF HRFQPTYPYL QHEIDLPPTI SLSDGEEPPP YQGPCTLQLR DPEQQLELNR ESVRAPPNRT IFDSDLMDSA RLGGPCPPSS NSGISATCYG SGGRMEGPPP TYSEVIGHYP GSSFQHQQSS GPPSLLEGTR LHHTHIAPLE SAAIWSKEKD KQKGHPL