FEATURES

FAMILY

DESCRIPTION

Also known as VPS39_HUMAN, VPS39, KIAA0770, TLP, VAM6. 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). Homooligomer (PubMed:11448994). Interacts with TGFBR2 and, less efficiently, with TGFBR1; interaction with TGFBR2 is independent of the receptor kinase activity and of the presence of TGF-beta. Also interacts with ACVR2B, but not with BMPR2. Interacts with SMAD4, preferentially following TGF-beta treatment. Does not interact with SAMD2 or SMAD3 (PubMed:12941698). Component of the putative homotypic fusion and vacuole protein sorting (HOPS) complex; the core of which composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, is associated with VPS39 and VPS41 (PubMed:23351085, PubMed:23901104, PubMed:25908847, PubMed:33422265). Interacts with PLEKHM2; involved in VPS39 recruitment to ARL8B-containing lysosomes (PubMed:25908847). Associates with adaptor protein complex 3 (AP-3) and clathrin:AP-3 complexes (By similarity). Interacts with STX17; this interaction is increased in the absence of TMEM39A (PubMed:31806350).

Also known as VPS39_HUMAN, VPS39, KIAA0770, TLP, VAM6. Regulator of TGF-beta/activin signaling, inhibiting SMAD3- and activating SMAD2-dependent transcription. Acts by interfering with SMAD3/SMAD ...

EXTERNAL LINKS

VPS39

Vam6/Vps39-like protein

VPS39

Molecular Synopsis