VPS33A VPS33A core subunit of CORVET and HOPS complexes [Homo sapiens (human)] - Gene

Summary

Official Symbol: VPS33Aprovided by HGNC
Official Full Name: VPS33A core subunit of CORVET and HOPS complexesprovided by HGNC
Primary source: HGNC:HGNC:18179
See related: Ensembl:ENSG00000139719 MIM:610034; AllianceGenome:HGNC:18179
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MPSPS
Summary: 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]
Expression: Ubiquitous expression in testis (RPKM 14.4), lymph node (RPKM 7.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q24.31

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (122229564..122266494, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (122225350..122262283, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (122714111..122751041, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The lysosomal disease caused by mutant VPS33A.
Title: The lysosomal disease caused by mutant VPS33A.
Since the inhibition of autolysosome formation plays a critical role in tuberculosis occurrence, these fi ndings suggests that miR-423-5p could suppress autophagosome-lysosome fusion by post-transcriptional regulation of VPS33A, which might be important for the occurrence of active tuberculosis.
Title: Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion.
It identified multimodal regulation of SNARE assembly by the Sec1/Munc18 (SM) protein VPS33A, mirroring other syntaxin-SM interactions and therefore suggesting a unified model of SM regulation.
Title: A VPS33A-binding motif on syntaxin 17 controls autophagy completion in mammalian cells.
Mutations in VPS33A is associated with mucopolysaccharidosis with severe systemic symptoms.
Title: Mutation in VPS33A affects metabolism of glycosaminoglycans: a new type of mucopolysaccharidosis with severe systemic symptoms.
Data suggest that accumulation of autophagosomes confers cytotoxicity in a number of cell types including neurons mimicking neurodegeneration; RNA interference of combinations of MTOR, VPS33A, and STX17 lead to accumulation of autophagosomes and cytotoxicity. (MTOR = mechanistic target of rapamycin kinase; VPS33A = vacuolar protein sorting 33A; STX17 = syntaxin 17)
Title: Accumulation of autophagosomes confers cytotoxicity.
The clinical phenotype and genetic studies support the suggestion that the siblings most probably have a novel disease very likely caused by a VPS33A gene defect.
Title: A probable new syndrome with the storage disease phenotype caused by the VPS33A gene mutation.
association of VPS33A with HOPS via its interaction with VPS16 is required for both endosome- and autophagosome-lysosome fusion
Title: Recruitment of VPS33A to HOPS by VPS16 Is Required for Lysosome Fusion with Endosomes and Autophagosomes.
Melanoma cells depleted of vacuolar protein sorting 33A protein have increased nuclear localization of cis-diaminedichloroplatinum II, increased nuclear DNA damage by platination, and increased apoptosis, resulting in increased treatment sensitivity.
Title: Targeting protein-trafficking pathways alters melanoma treatment sensitivity.
VPS33A is mutated in Hermansky-Pudlak syndrome and may have a role in melanogenesis
Title: The mouse organellar biogenesis mutant buff results from a mutation in Vps33a, a homologue of yeast vps33 and Drosophila carnation.
A and B classes reflect the evolution of organelle/tissue-specific functions
Title: Comparative evolutionary analysis of VPS33 homologues: genetic and functional insights.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Mucopolysaccharidosis-plus syndrome MedGen: C4310627 OMIM: 617303 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SGC34693 (e-PCR)
- UniSTS:83485

STS-R99269 (e-PCR)
- UniSTS:12102

G32482 (e-PCR)
- UniSTS:117067

D6S1375 (e-PCR)
- UniSTS:153690

D10S16 (e-PCR)
- UniSTS:155756

A009E34 (e-PCR)
- UniSTS:56747

RH44549 (e-PCR)
- UniSTS:81602

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in autophagosome maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endosomal vesicle fusion	NAS Non-traceable Author Statement more info	PubMed
involved_in endosome to lysosome transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular protein transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in lysosome localization	IDA Inferred from Direct Assay more info	PubMed
involved_in melanosome localization	IDA Inferred from Direct Assay more info	PubMed
involved_in platelet formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of SNARE complex assembly	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of developmental pigmentation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of lysosomal lumen pH	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vesicle-mediated transport	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within vesicle-mediated transport	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of AP-3 adaptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of CORVET complex	IBA Inferred from Biological aspect of Ancestor more info
part_of CORVET complex	NAS Non-traceable Author Statement more info	PubMed
part_of HOPS complex	IDA Inferred from Direct Assay more info	PubMed
part_of HOPS complex	NAS Non-traceable Author Statement more info	PubMed
located_in autophagosome	ISS Inferred from Sequence or Structural Similarity more info
part_of clathrin complex	IDA Inferred from Direct Assay more info	PubMed
located_in clathrin-coated vesicle	IEA Inferred from Electronic Annotation more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	TAS Traceable Author Statement more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in late endosome membrane	IEA Inferred from Electronic Annotation more info
located_in lysosomal membrane	HDA more info	PubMed
is_active_in lysosome	IBA Inferred from Biological aspect of Ancestor more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: vacuolar protein sorting-associated protein 33A

Names: VPS33A, CORVET/HOPS core subunit; vacuolar protein sorting 33 homolog A; vacuolar protein sorting 33A

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_054909.1 RefSeqGene

Range

5028..41958

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001351018.2 → NP_001337947.1 vacuolar protein sorting-associated protein 33A isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate exon in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AC048338, AI830457

UniProtKB/TrEMBL

B2RDH6

Related

ENSP00000519333.1, ENST00000714042.1

Conserved Domains (1) summary

pfam00995
Location:23 → 573

Sec1; Sec1 family
NM_001351019.2 → NP_001337948.1 vacuolar protein sorting-associated protein 33A isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate exon in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

AC048338, AI830457

UniProtKB/TrEMBL

B2RDH6

Related

ENSP00000519334.1, ENST00000714043.1

Conserved Domains (1) summary

pfam00995
Location:18 → 568

Sec1; Sec1 family
NM_001351020.2 → NP_001337949.1 vacuolar protein sorting-associated protein 33A isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks two alternate exons in the central coding region but maintains the reading frame, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.

Source sequence(s)

AC048338, AI830457

UniProtKB/TrEMBL

A0A2R8Y5U3

Related

ENSP00000495062.2, ENST00000541169.2

Conserved Domains (1) summary

pfam00995
Location:34 → 477

Sec1; Sec1 family
NM_001351021.2 → NP_001337950.1 vacuolar protein sorting-associated protein 33A isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks a portion of the 3' coding region, includes an alternate penultimate exon, and differs in the 3' UTR, compared to variant 1. The encoded isoform (5) has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC048338, BF510648, BX337807, CK024047

Consensus CDS

CCDS86339.1

UniProtKB/TrEMBL

A0AAQ5BHF8, F5H6Y0

Related

ENSP00000442951.1, ENST00000451053.3

Conserved Domains (1) summary

cl15415
Location:34 → 165

Sec1; Sec1 family
NM_022916.6 → NP_075067.2 vacuolar protein sorting-associated protein 33A isoform 1

See identical proteins and their annotated locations for NP_075067.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC048338, AI830457, BC016617, BP199163

Consensus CDS

CCDS9231.1

UniProtKB/Swiss-Prot

Q547V4, Q96AX1, Q9H5Q0

UniProtKB/TrEMBL

B2RDH6

Related

ENSP00000267199.3, ENST00000267199.9

Conserved Domains (1) summary

pfam00995
Location:34 → 584

Sec1; Sec1 family