VPS33A [The Human Chemical-Genetic Interaction Map Project]

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======= VPS33A =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: VPS33A
  * **<color #00a2e8>Official Name</color>**: VPS33A core subunit of CORVET and HOPS complexes
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=65082|65082]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q96AX1|Q96AX1]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=VPS33A&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20VPS33A|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/610034|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a tethering protein and a core subunit of the homotypic fusion and protein sorting (HOPS) complex. The HOPS complex and a second endosomal tethering complex called the class C core vacuole/endosome tethering (CORVET) complex, perform diverse functions in endocytosis including membrane tethering, RabGTPase interaction, activation and proofreading of synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) assembly to drive membrane fusion, and endosome-to-cytoskeleton attachment. The HOPS complex controls endosome maturation as well as endosome traffic to the lysosome. This complex is essential for vacuolar fusion and is required for adaptor protein complex 3-dependent transport from the golgi to the vacuole. The encoded protein belongs to the Sec1/Munc18 (SM) family of SNARE-mediated membrane fusion regulators. Naturally occurring mutations in this gene are associated with a novel mucopolysaccharidosis-like disease. [provided by RefSeq, Apr 2017]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are 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. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:23351085, PubMed:24554770, PubMed:25266290, PubMed:25783203). Required for fusion of endosomes and autophagosomes with lysosomes; the function is dependent on its association with VPS16 but not VIPAS39 (PubMed:25783203). The function in autophagosome-lysosome fusion implicates STX17 but not UVRAG (PubMed:24554770). {ECO:0000269|PubMed:24554770, ECO:0000269|PubMed:25783203, ECO:0000305|PubMed:23351085, ECO:0000305|PubMed:25266290, ECO:0000305|PubMed:25783203}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Sec1|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|clathrin complex|
|AP-3 adaptor complex|
|regulation of lysosomal lumen pH|
|HOPS complex|
|regulation of developmental pigmentation|
|platelet formation|
|platelet morphogenesis|
|melanosome localization|
|pigment granule localization|
|autophagosome maturation|
|vesicle docking involved in exocytosis|
|lysosome localization|
|cellular pigmentation|
|endosome to lysosome transport|
|clathrin-coated vesicle|
|lysosome organization|
|lytic vacuole organization|
|vesicle docking|
|exocytic process|
|autophagosome|
|regulation of intracellular pH|
|regulation of cellular pH|
|pigmentation|
|regulation of pH|
|lysosomal transport|
|cellular monovalent inorganic cation homeostasis|
|late endosome membrane|
|late endosome|
|vacuole organization|
|monovalent inorganic cation homeostasis|
|vacuolar transport|
|macroautophagy|
|organelle localization by membrane tethering|
|membrane docking|
|vesicle localization|
|myeloid cell differentiation|
|protein-containing complex disassembly|
|early endosome|
|autophagy|
|process utilizing autophagic mechanism|
|lysosomal membrane|
|cellular component disassembly|
|cell morphogenesis involved in differentiation|
|hemopoiesis|
|organelle localization|
|hematopoietic or lymphoid organ development|
|cellular cation homeostasis|
|cellular ion homeostasis|
|immune system development|
|perinuclear region of cytoplasm|
|cation homeostasis|
|inorganic ion homeostasis|
|cell morphogenesis|
|cellular chemical homeostasis|
|ion homeostasis|
|exocytosis|
|cellular component morphogenesis|
|anatomical structure formation involved in morphogenesis|
|cellular homeostasis|
|secretion by cell|
|export from cell|
|chemical homeostasis|
|secretion|
|protein transport|
|intracellular transport|
|peptide transport|
|amide transport|
|establishment of protein localization|
|homeostatic process|
|cell development|
|cellular catabolic process|
|establishment of localization in cell|
|nitrogen compound transport|
|protein-containing complex subunit organization|
|vesicle-mediated transport|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp227|Cryptotanshinone 12μM R05 exp227]]|-2.18|
|[[:results:exp498|Lead acetate 2000μM R08 exp498 no dilution day6]]|-1.88|
|[[:results:exp169|BH1 1μM R04 exp169]]|-1.81|
|[[:results:exp477|DKK1 89ng/ml R08 exp477]]|-1.81|
|[[:results:exp89|Vemurafenib 6.6μM R02 exp89]]|-1.81|
|[[:results:exp164|Q15 1 to 2μM on day4 R04 exp164]]|-1.78|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 315/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|10/28|
|blood|19/28|
|bone|8/26|
|breast|14/33|
|central nervous system|22/56|
|cervix|1/4|
|colorectal|7/17|
|esophagus|1/13|
|fibroblast|1/1|
|gastric|7/16|
|kidney|13/21|
|liver|10/20|
|lung|37/75|
|lymphocyte|9/16|
|ovary|12/26|
|pancreas|6/24|
|peripheral nervous system|2/16|
|plasma cell|10/15|
|prostate|1/1|
|skin|6/24|
|soft tissue|5/9|
|thyroid|0/2|
|upper aerodigestive|10/22|
|urinary tract|12/29|
|uterus|2/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 1806
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.46 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='VPS33A Expression in NALM6 Cells: 5.46'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>