VPS39

Regulator of TGF-beta/activin signaling, inhibiting SMAD3- and activating SMAD2-dependent transcription. Acts by interfering with SMAD3/SMAD4 complex formation, this would lead to inhibition of SMAD3-dependent transcription and relieve SMAD3 inhibition of SMAD2-dependent promoters, thus increasing SMAD2-dependent transcription. Does not affect TGF-beta-induced SMAD2 or SMAD3 phosphorylation, nor SMAD2/SMAD4 complex formation.

Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Acts as a component of the putative HOPS endosomal tethering complex which is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes (PubMed:23351085). Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes (PubMed:11448994, PubMed:23167963, PubMed:23351085). Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203).

Belongs to the VAM6/VPS39 family.

Widely expressed, with highest levels in heart, skeletal muscle, kidney, pancreas, brain, placenta and spleen.

• Cytoplasm
• Lysosome membrane
• Peripheral membrane protein
• Late endosome membrane
• Peripheral membrane protein
• Colocalizes with TGFBR1 and TGFBR2 in cytoplasmic vesicular structures and most prominently in cortical vesicles.
• (Microbial infection) Sequestrated at the late endosome by SARS coronavirus-2/SARS-CoV-2 ORF3A protein.

KIAA0770, TLP, VAM6, VPS39, Vam6/Vps39-like protein, TRAP1-like protein, hVam6p

• entrezGene:23339
• omim:612188
• swissprot:Q96JC1

Proteins

Neuroscience

101809Da