VPS33B
Function
May play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes. Required for proper trafficking and targeting of the collagen-modifying enzyme lysyl hydroxylase 3 (LH3) to intracellular collagen (PubMed:28017832). Mediates phagolysosomal fusion in macrophages (PubMed:18474358). Proposed to be involved in endosomal maturation implicating VIPAS39. In epithelial cells, the VPS33B:VIPAS39 complex may play a role in the apical recycling pathway and in the maintenance of the apical-basolateral polarity (PubMed:20190753). Seems to be involved in the sorting of specific cargos from the trans-Golgi network to alpha-granule-destined multivesicular bodies (MVBs) promoting MVBs maturation in megakaryocytes (By similarity).
Involvement in disease
Arthrogryposis, renal dysfunction and cholestasis syndrome 1
ARCS1
A multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase activity. Platelet dysfunction is common.
None
The disease is caused by variants affecting the gene represented in this entry.
Keratoderma-ichthyosis-deafness syndrome, autosomal recessive
KDIDAR
An autosomal recessive disorder characterized by severe palmoplantar keratoderma, generalized ichthyosis, and sensorineural bilateral hearing loss. Additional variable features include contractures, mild bleeding diathesis, and psychomotor retardation.
None
The disease is caused by variants affecting the gene represented in this entry.
Cholestasis, progressive familial intrahepatic, 12
PFIC12
A form of progressive cholestasis, a disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease. PFIC12 is an autosomal recessive form characterized by neonatal-onset jaundice and conjugated hyperbilirubinemia, associated with intense pruritus.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated on tyrosine residues.
(Microbial infection) Dephosphorylated by M.tuberculosis PtpA, which induces the reduction of host phagolysosome fusion in M.tuberculosis-infected macrophages.
Sequence Similarities
Belongs to the STXBP/unc-18/SEC1 family.
Tissue Specificity
Ubiquitous; highly expressed in testis and low expression in the lung.
Cellular localization
- Late endosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Lysosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Early endosome
- Cytoplasmic vesicle
- Clathrin-coated vesicle
- Recycling endosome
- Colocalizes in clusters with VIPAS39 at cytoplasmic organelles (PubMed:19109425, PubMed:31479177). Colocalizes with RAB11A and VIPAS39 on recycling endosomes (PubMed:22753090). Colocalizes with AP-3, clathrin, Rab5 and Rab7b (PubMed:21411634). Colocalizes with M.tuberculosis PtpA in the cytosol of tuberculosis-infected macrophages and associates with phagosomes (PubMed:18474358).
Alternative names
Vacuolar protein sorting-associated protein 33B, hVPS33B, VPS33B