VPS39

This gene encodes a protein that may promote clustering and fusion of late endosomes and lysosomes. The protein may also act as an adaptor protein that modulates the transforming growth factor-beta response by coupling the transforming growth factor-beta receptor complex to the Smad pathway. Alternative splicing results in multiple transcript variants.

Full Name

VPS39, HOPS Complex Subunit

Function

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:23351085, PubMed:23167963).
Required for fusion of endosomes and autophagosomes with lysosomes (PubMed:25783203).

Biological Process

Biological Process autophagosome-lysosome fusion Source:UniProtKB1 Publication
Biological Process autophagy Source:UniProtKB1 Publication
Biological Process endocytic recycling Source:UniProtKB1 Publication
Biological Process endosomal vesicle fusion Source:UniProtKB1 Publication
Biological Process endosome to lysosome transport Source:UniProtKB2 Publications
Biological Process intracellular protein transport Source:InterPro
Biological Process late endosome to lysosome transport Source:UniProtKB1 Publication
Biological Process regulation of SNARE complex assembly Source:ComplexPortal1 Publication

Cellular Location

Cytoplasm
Lysosome membrane
Late endosome membrane
Colocalizes with TGFBR1 and TGFBR2 in cytoplasmic vesicular structures and most prominently in cortical vesicles.