Vap33 VAMP-associated protein 33kDa [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Vap33provided by FlyBase
Official Full Name: VAMP-associated protein 33kDaprovided by FlyBase
Primary source: FLYBASE:FBgn0029687
Locus tag: Dmel_CG5014
See related: AllianceGenome:FB:FBgn0029687
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: anon-EST:Liang-2.42; anon-WO03040301.124; BcDNA:GM03307; CG5014; clone 2.42; Dmel\CG5014; dvap; dVAP; DVAP; dVAP-33; DVAP-33A; dVAP-A; dvap33a; dVAP33A; DVAP33A; l(1)G0231; VAP; VAP-33; Vap-33-1; VAP-33-1; vap-33A; Vap-33A; vap33; VAP33; vap33-1; Vap33-1; VAP33-A; VAP33A; vapb; VAPB
Summary: Predicted to enable protein-membrane adaptor activity. Involved in several processes, including cytoplasmic microtubule organization; defense response to Gram-negative bacterium; and synapse organization. Located in endoplasmic reticulum; extracellular space; and plasma membrane. Is active in several cellular components, including cholinergic synapse; presynaptic cytoskeleton; and presynaptic membrane. Is expressed in adult head; adult heart; and organism. Used to study amyotrophic lateral sclerosis; amyotrophic lateral sclerosis type 8; autosomal dominant adult-onset proximal spinal muscular atrophy; motor neuron disease; and neurodegenerative disease. Human ortholog(s) of this gene implicated in amyotrophic lateral sclerosis; amyotrophic lateral sclerosis type 8; autosomal dominant adult-onset proximal spinal muscular atrophy; and spinal muscular atrophy. Orthologous to several human genes including VAPB (VAMP associated protein B and C). [provided by Alliance of Genome Resources, Nov 2024]
Orthologs: all
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Genomic context

Location:: 3F9-3F9; 1-5 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	X	NC_004354.4 (3948975..3955442)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	X	NC_004354.3 (3843008..3849475)

Chromosome X - NC_004354.4 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

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Secretion of endoplasmic reticulum protein VAPB/ALS8 requires topological inversion.
Title: Secretion of endoplasmic reticulum protein VAPB/ALS8 requires topological inversion.
Age-dependent dynamics of neuronal VAPB[ALS] inclusions in the adult brain.
Title: Age-dependent dynamics of neuronal VAPB(ALS) inclusions in the adult brain.
The Drosophila tumour suppressor Lgl and Vap33 activate the Hippo pathway through a dual mechanism.
Title: The Drosophila tumour suppressor Lgl and Vap33 activate the Hippo pathway through a dual mechanism.
Amyotrophic lateral sclerosis-associated Vap33 is required for maintaining neuronal dendrite morphology and organelle distribution in Drosophila.
Title: Amyotrophic lateral sclerosis-associated Vap33 is required for maintaining neuronal dendrite morphology and organelle distribution in Drosophila.
VAP proteins (VAPs) mediate ER to Golgi tethering and their loss may affect phosphatidylinositol-4-phosphate (PtdIns4P) transfer between these organelles. Loss of VAPs elevates PtdIns4P levels in the Golgi, leading to an expansion of the endosomal pool derived from the Golgi.
Title: VAMP associated proteins are required for autophagic and lysosomal degradation by promoting a PtdIns4P-mediated endosomal pathway.
Lgl promoted the activity of the V-ATPase by interacting with Vap33 (VAMP-associated protein of 33 kDa). Vap33 physically and genetically interacted with Lgl and V-ATPase subunits and repressed V-ATPase-mediated endosomal vesicle acidification and Notch signaling.
Title: Lgl reduces endosomal vesicle acidification and Notch signaling by promoting the interaction between Vap33 and the V-ATPase complex.
an interesting interplay between SOD1, ROS and mTOR signalling that regulates the dynamics of VAP aggregation, is reported.
Title: SOD1 activity threshold and TOR signalling modulate VAP(P58S) aggregation via reactive oxygen species-induced proteasomal degradation in a Drosophila model of amyotrophic lateral sclerosis.
the relationship between DVAP-P58 phenotypes and the Drosophila modifiers, raises the possibility that pharmacological manipulation of these genes may assist in developing treatments to ameliorate or prevent ALS-related abnormalities
Title: Network analyses reveal novel aspects of ALS pathogenesis.
We propose that Vap function is required in neurons to selectively traffic proteins to axons, and disruption of this function may contribute to the pathology of ALS.
Title: Drosophila Vap-33 is required for axonal localization of Dscam isoforms.
findings suggest VAP(P58S) may function as a dominant negative; study also demonstrated that the ALS8 mutation in dVAP33A interferes with BMP signaling pathways at the neuromuscular junction, identifying a new mechanism underlying pathogenesis of ALS8
Title: A Drosophila model of ALS: human ALS-associated mutation in VAP33A suggests a dominant negative mechanism.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables protein-membrane adaptor activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in axo-dendritic transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cytoplasmic microtubule organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to Gram-negative bacterium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endoplasmic reticulum membrane organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in endoplasmic reticulum-plasma membrane tethering	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuromuscular junction development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neurotransmitter secretion	NAS Non-traceable Author Statement more info	PubMed
involved_in phosphatidylinositol metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synapse maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic vesicle priming	NAS Non-traceable Author Statement more info	PubMed
involved_in terminal button organization	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cholinergic synapse	IDA Inferred from Direct Assay more info	PubMed
located_in endomembrane system	HDA more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
is_active_in endoplasmic reticulum membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
is_active_in neuromuscular junction	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
is_active_in presynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
located_in synaptic vesicle	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: VAMP-associated protein 33kDa

Names: CG5014-PA; CG5014-PB; CG5014-PC; CG5014-PE; VAMP-associated protein of 33kDa A; VAMP-associated protein of 33kDa ortholog A; Vap-33-1; Vap33-1; Vap33-PA; Vap33-PB; Vap33-PC; Vap33-PE

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NC_004354.4 Reference assembly

Range

3948975..3955442

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_206623.2 → NP_996346.2 VAMP-associated protein 33kDa, isoform E [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_996346.2

Status: REVIEWED

UniProtKB/TrEMBL

Q7KVX4, Q9W4N8

Conserved Domains (1) summary

pfam00635
Location:9 → 115

Motile_Sperm; MSP (Major sperm protein) domain
NM_130731.3 → NP_570087.1 VAMP-associated protein 33kDa, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_570087.1

Status: REVIEWED

UniProtKB/TrEMBL

Q7KVX4, Q9W4N8

Related

FBpp0070589

Conserved Domains (1) summary

pfam00635
Location:9 → 115

Motile_Sperm; MSP (Major sperm protein) domain
NM_206625.2 → NP_996348.1 VAMP-associated protein 33kDa, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_996348.1

Status: REVIEWED

UniProtKB/TrEMBL

Q7KVX5

Conserved Domains (1) summary

pfam00635
Location:9 → 115

Motile_Sperm; MSP (Major sperm protein) domain
NM_206624.2 → NP_996347.1 VAMP-associated protein 33kDa, isoform C [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_996347.1

Status: REVIEWED

UniProtKB/TrEMBL

Q7KVX4, Q9W4N8

Conserved Domains (1) summary

pfam00635
Location:9 → 115

Motile_Sperm; MSP (Major sperm protein) domain