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 . Involved in homotypic vesicle fusions between late endosomes and in heterotypic fusions between late endosomes and lysosomes . Required for fusion of endosomes and autophagosomes with lysosomes .
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. .
Widely expressed, with highest levels in heart, skeletal muscle, kidney, pancreas, brain, placenta and spleen.
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