12q24.31 View the map and BAC contig (data from UCSC genome browser).
VPS33A/NM_022916: 13 exons, 34,922bp, chr12:121,153,622-121,188,543.
The figure below shows the structure of the VPS33A gene (data from UCSC genome browser).
Search the 5'UTR and 1kb upstream regions (human and mouse) by CONREAL with 80% Position Weight Matrices (PWMs) threshold (view results here).
Tissue specificity: moderate systemic expression.
BMR: Bone marrow; SPL: Spleen; TMS: Thymus; BRN: Brain; SPC: Spinal cord; HRT: Heart; MSL: Skeletal muscle; LVR; Liver; PNC: Pancreas; PST: Prostate; KDN: Kidney; LNG: Lung. (data from GeneCards )
|Protein||NP_084205 (598aa)||NP_075250 (597aa)||13152 (577aa)||AAD38513 (617aa)||Vps33p |
(1) Domains predicted by SMART:
a) low complexity: 12 - 27
b) low complexity: 225 - 237
(2) Transmembrane domains predicted by SOSUI: none.
(3) CDD domain: pfam00995.11, Sec1: Sec1 family.
(4) Graphic view of InterPro domain structure.
(1) Predicted results by ScanProsite:
a) Protein kinase C phosphorylation site : [occurs frequently]
65 - 67 TlK, 312 - 314 SkK, 386 - 388 TdK, 465 - 467 TiR, 469 - 471 TlR, 496 - 498 SvR, 578 - 580 TtK.
b) N-myristoylation site : [occurs frequently]
129 - 134 GVlgSF,215 - 220 GSqnSI, 255 - 260 GIqnSY, 308 - 313 GSvlSK, 349 - 354 GSlaNH, 458 - 463 GGrnNY, 552 - 557 GVtfAE.
c) N-glycosylation site : [occurs frequently]
353 - 356 NHTS, 583 - 586 NGTS.
d) Tyrosine sulfation site : [occurs frequently]
157 - 171 egafkecYlegdqts, 289 - 303 lnsaeelYaeirdkn.
(2) Predicted results of subprograms by PSORT II:
a) N-terminal signal peptide: none
b) KDEL ER retention motif in the C-terminus: none
c) ER Membrane Retention Signals: KKXX-like motif in the C-terminus: MEKP
d) VAC possible vacuolar targeting motif: none
e) Actinin-type actin-binding motif: type 1: none; type 2: none
f) Prenylation motif: none
g) memYQRL transport motif from cell surface to Golgi: none
h) Tyrosines in the tail: too long tail
i) Dileucine motif in the tail: found - LL at 54
(1) ModBase: None
(2) 3D models predicted by SPARKS (fold recognition) below. View the models by PDB2MGIF.
This protein does not exist in the current release of SWISS-2DPAGE.
Computed theoretical MW=67,611Da, pI=6.50 (NP_075067).
a) Process: Golgi-to-vacuole protein transport, protein secretion (overview of trafficking pathway here).
b) Belongs to the STXBP/UNC-18/SEC1 family.
c) Component of membrane.
Cytoplasmic, peripheral membrane protein associated with late endosomes/lysosomes. Vps33p is an ATP-binding protein that localizes to the cytosol in an energy-dependent manner (Gerhardts, et al; Banta, et al).
This gene is a member of the Sec-1 domain family, and it encodes a protein similar to the yeast class C Vps33 protein. A large hetero-oligomeric class C Vps complex consists of VPS33 together with VPS11, VPS16, VPS18, and probably also the VPS39 and VPS41 proteins (Huizing, et al; Rieder, et al ). In yeast, a 38S complex consisting of both Vam2/6p and the class C Vps proteins, which is termed as HOPS, is responsible for homotypic fusion and vacuole protein sorting (Seals, et al). The C-Vps complex binds to Vam3-Vti1-Vam7 paired SNARE complexes and STX7 (Sato, et al). At the endosome, Vps33p and other class C members exist as a complex with Vps8p, a protein previously known to act in transport between the late Golgi and the endosome. C. elegans SPE-39 interacts in vitro with both VPS33A and VPS33B, whereas RNA interference of VPS33B causes spe-39-like spermatogenesis defects. The human SPE-39 orthologue C14orf133 also interacts with VPS33 homologues and both coimmunoprecipitates and cosediments with other HOPS subunits. SPE-39 knockdown in cultured human cells altered the morphology of syntaxin 7-, syntaxin 8-, and syntaxin 13-positive endosomes (Zhu, et al).
Vps33p also interacts with Pep12p, a known interactor of the SM protein Vps45p (Subramanian, et al). A novel endosomal tethering (CORVET) complex, which interacts with the Rab GTPase Vps21, has been described. Both HOPS and CORVET complexes share the four class C Vps proteins: Vps11, Vps16, Vps18, and Vps33. The HOPS complex, in addition, contains Vps41/Vam2 and Vam6, whereas the CORVET complex has the Vps41 homolog Vps8 and the (h)Vam6 homolog Vps3. The CORVET and HOPS complexes can interconvert which leads to two additional intermediate complexes, both consisting of the class C core bound to Vam6-Vps8 or Vps3-Vps41 (Peplowska, et al). In drosophila, Deep orange and carnation reside in a protein complex that localizes to endosomal compartments (Sevrioukov, et al).
7 proteins are shown to be associated with YLR396C/VPS33 in Yeast GRID.
No entry for the Vps33a drosophila homolog CG12230/car in CuraGen interaction database.
The mammalian class C VPS proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway (view diagram of Class C Vps pathway here). The Class C Vps complex plays essential roles in the processes of membrane docking and fusion at both the Golgi-to-endosome and endosome-to-vacuole stages of transport. (Peterson, et al; Sato, et al; Pevsner, et al ). Vps33p functions at multiple trafficking steps and is not limited to action at the vacuolar membrane (Subramanian, et al).