VAV1 vav guanine nucleotide exchange factor 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: VAV1provided by HGNC
Official Full Name: vav guanine nucleotide exchange factor 1provided by HGNC
Primary source: HGNC:HGNC:12657
See related: Ensembl:ENSG00000141968 MIM:164875; AllianceGenome:HGNC:12657
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: VAV
Summary: This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. The encoded protein is important in hematopoiesis, playing a role in T-cell and B-cell development and activation. The encoded protein has been identified as the specific binding partner of Nef proteins from HIV-1. Coexpression and binding of these partners initiates profound morphological changes, cytoskeletal rearrangements and the JNK/SAPK signaling cascade, leading to increased levels of viral transcription and replication. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Apr 2012]
Expression: Broad expression in lymph node (RPKM 23.7), appendix (RPKM 21.5) and 16 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (6772708..6857361)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (6762101..6846684)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (6772719..6857372)

Chromosome 19 - NC_000019.10 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
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?

Sex-dependent expression levels of VAV1 and P2X7 in PBMC of multiple sclerosis patients.
Title: Sex-dependent expression levels of VAV1 and P2X7 in PBMC of multiple sclerosis patients.
Vav1-dependent Rac1 activation mediates hypoxia-induced gemcitabine resistance in pancreatic ductal adenocarcinoma cells through upregulation of HIF-1alpha expression.
Title: Vav1-dependent Rac1 activation mediates hypoxia-induced gemcitabine resistance in pancreatic ductal adenocarcinoma cells through upregulation of HIF-1α expression.
Unraveling the Oncogenic Potential of VAV1 in Human Cancer: Lessons from Mouse Models.
Title: Unraveling the Oncogenic Potential of VAV1 in Human Cancer: Lessons from Mouse Models.
RhoA G17E/Vav1 Signaling Induces Cancer Invasion via Matrix Metalloproteinase-9 in Gastric Cancer.
Title: RhoA G17E/Vav1 Signaling Induces Cancer Invasion via Matrix Metalloproteinase-9 in Gastric Cancer.
Spatially resolved in silico modeling of NKG2D signaling kinetics suggests a key role of NKG2D and Vav1 Co-clustering in generating natural killer cell activation.
Title: Spatially resolved in silico modeling of NKG2D signaling kinetics suggests a key role of NKG2D and Vav1 Co-clustering in generating natural killer cell activation.
Vav1 Promotes B-Cell Lymphoma Development.
Title: Vav1 Promotes B-Cell Lymphoma Development.
Regulatory interplay between Vav1, Syk and beta-catenin occurs in lung cancer cells.
Title: Regulatory interplay between Vav1, Syk and β-catenin occurs in lung cancer cells.
Identification of molecular subtyping system and four-gene prognostic signature with immune-related genes for uveal melanoma.
Title: Identification of molecular subtyping system and four-gene prognostic signature with immune-related genes for uveal melanoma.
Vav1 Sustains the In Vitro Differentiation of Normal and Tumor Precursors to Insulin Producing Cells Induced by all-Trans Retinoic Acid (ATRA).
Title: Vav1 Sustains the In Vitro Differentiation of Normal and Tumor Precursors to Insulin Producing Cells Induced by all-Trans Retinoic Acid (ATRA).
Cancer-associated mutations in VAV1 trigger variegated signaling outputs and T-cell lymphomagenesis.
Title: Cancer-associated mutations in VAV1 trigger variegated signaling outputs and T-cell lymphomagenesis.

Submit: New GeneRIF Correction See all GeneRIFs (117)

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

EBI GWAS Catalog

Description
Exploring the genetic basis of chronic periodontitis: a genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 alone or CD4/gp160 cross-linking induces tyrosine phosphorylation of intracellular substrates p59fyn, zap 70, and p95vav and also leads to ras activation	PubMed
Nef	nef	The association of HIV-1 Nef with Vav1, Pak2, and Nck1 is greatly reduced in SLP76-deficient T cells	PubMed
	nef	Nef-mediated microdomain recruitment of Vav1 is associated with the Nef-p21-activated kinase 2 (PAK2) signalosome. Nef residue F195 is identified as critical for Nef-mediated raft recruitment of Vav1	PubMed
	nef	The interaction of HIV-1 Nef with Vav is detected by pull-down assays; mutations in the Nef PXXP motif maintain some residual binding capacity to Vav	PubMed
	nef	The C-terminal SH3 domain of Vav binds to the PXXP motif in HIV-1 Nef and this interaction activates Vav and its downstream effectors, leading to morphological changes, cytoskeletal rearrangements, and the activation of the JNK/SAPK cascade	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D19S534 (e-PCR)
- UniSTS:148824

MARC_12285-12286:1005663674:1 (e-PCR)
- UniSTS:267396

MARC_12285-12286:1008002533:1 (e-PCR)
- UniSTS:267396

RH80857 (e-PCR)
- UniSTS:91336

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables guanyl-nucleotide exchange factor activity	EXP Inferred from Experiment more info	PubMed
enables guanyl-nucleotide exchange factor activity	IBA Inferred from Biological aspect of Ancestor more info
enables guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
enables guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables phosphorylation-dependent protein binding	IEA Inferred from Electronic Annotation more info
enables phosphotyrosine residue binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Fc-epsilon receptor signaling pathway	TAS Traceable Author Statement more info
involved_in Fc-gamma receptor signaling pathway involved in phagocytosis	TAS Traceable Author Statement more info
involved_in G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in T cell costimulation	IDA Inferred from Direct Assay more info	PubMed
involved_in T cell costimulation	TAS Traceable Author Statement more info
involved_in T cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to xenobiotic stimulus	TAS Traceable Author Statement more info
involved_in immune response-regulating cell surface receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in integrin-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in natural killer cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in natural killer cell mediated cytotoxicity	IDA Inferred from Direct Assay more info	PubMed
involved_in neutrophil chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in platelet activation	TAS Traceable Author Statement more info
involved_in positive regulation of natural killer cell mediated cytotoxicity	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in reactive oxygen species metabolic process	IEA Inferred from Electronic Annotation more info
involved_in regulation of GTPase activity	IGI Inferred from Genetic Interaction more info	PubMed
NOT involved_in regulation of cell size	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of cell size	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info
involved_in small GTPase-mediated signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in vascular endothelial growth factor receptor signaling pathway	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: proto-oncogene vav

Names: vav 1 guanine nucleotide exchange factor; vav 1 oncogene

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.

mRNA and Protein(s)

NM_001258206.2 → NP_001245135.1 proto-oncogene vav isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AK225710, BC013361, DC408645

Consensus CDS

CCDS59341.1

UniProtKB/TrEMBL

A0A0A0MR07, B2R8B5

Related

ENSP00000302269.2, ENST00000304076.6

Conserved Domains (7) summary

cd10405
Location:643 → 745

SH2_Vav1; Src homology 2 (SH2) domain found in the Vav1 proteins

cd11976
Location:764 → 817

SH3_VAV1_2; C-terminal (or second) Src homology 3 domain of VAV1 protein

cd00160
Location:195 → 371

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd01223
Location:385 → 508

PH_Vav; Vav pleckstrin homology (PH) domain

pfam00130
Location:516 → 567

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

cl00030
Location:18 → 102

CH; Calponin homology domain; actin-binding domain which may be present as a single copy or in tandem repeats (which increases binding affinity). The CH domain is found in cytoskeletal and signal transduction proteins, including actin-binding proteins like ...

cl17036
Location:596 → 639

SH3; Src Homology 3 domain superfamily
NM_001258207.2 → NP_001245136.1 proto-oncogene vav isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an exon in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.

Source sequence(s)

AK301128, BC013361, DC408645

Consensus CDS

CCDS59342.1

UniProtKB/TrEMBL

B2R8B5

Related

ENSP00000469450.1, ENST00000596764.5

Conserved Domains (7) summary

cd10405
Location:633 → 735

SH2_Vav1; Src homology 2 (SH2) domain found in the Vav1 proteins

cd11976
Location:754 → 807

SH3_VAV1_2; C-terminal (or second) Src homology 3 domain of VAV1 protein

cd11979
Location:564 → 626

SH3_VAV1_1; First Src homology 3 domain of VAV1 protein

smart00325
Location:187 → 340

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

cd01223
Location:353 → 476

PH_Vav; Vav pleckstrin homology (PH) domain

pfam00130
Location:484 → 535

C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

cl00030
Location:18 → 102

CH; Calponin homology domain; actin-binding domain which may be present as a single copy or in tandem repeats (which increases binding affinity). The CH domain is found in cytoskeletal and signal transduction proteins, including actin-binding proteins like ...
NM_005428.4 → NP_005419.2 proto-oncogene vav isoform 1

See identical proteins and their annotated locations for NP_005419.2

Status: REVIEWED

Description

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

Source sequence(s)

AK313307, BC013361, DC408645

Consensus CDS

CCDS12174.1

UniProtKB/Swiss-Prot

B4DVK9, M0QXX6, P15498, Q15860

UniProtKB/TrEMBL

B2R8B5

Related

ENSP00000472929.1, ENST00000602142.6

Conserved Domains (7) summary

cd10405
Location:665 → 767

SH2_Vav1; Src homology 2 (SH2) domain found in the Vav1 proteins

cd11976
Location:786 → 839

SH3_VAV1_2; C-terminal (or second) Src homology 3 domain of VAV1 protein

cd11979
Location:596 → 658

SH3_VAV1_1; First Src homology 3 domain of VAV1 protein

cd00160
Location:195 → 371

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd01223
Location:385 → 508

PH_Vav; Vav pleckstrin homology (PH) domain

cd21262
Location:2 → 121

CH_VAV1; calponin homology (CH) domain found in VAV1 protein

cd20867
Location:510 → 566

C1_VAV1; protein kinase C conserved region 1 (C1 domain) found in VAV1 protein

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

6772708..6857361

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005259642.2 → XP_005259699.1 proto-oncogene vav isoform X1

UniProtKB/TrEMBL

B2R8B5

Conserved Domains (6) summary

cd11979
Location:596 → 658

SH3_VAV1_1; First Src homology 3 domain of VAV1 protein

cd00160
Location:195 → 371

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd01223
Location:385 → 508

PH_Vav; Vav pleckstrin homology (PH) domain

cd21262
Location:2 → 121

CH_VAV1; calponin homology (CH) domain found in VAV1 protein

cd20867
Location:510 → 566

C1_VAV1; protein kinase C conserved region 1 (C1 domain) found in VAV1 protein

cl15255
Location:665 → 739

SH2; Src homology 2 (SH2) domain