WASF2 WASP family member 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: WASF2provided by HGNC
Official Full Name: WASP family member 2provided by HGNC
Primary source: HGNC:HGNC:12733
See related: Ensembl:ENSG00000158195 MIM:605875; AllianceGenome:HGNC:12733
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: IMD2; SCAR2; WASF4; WAVE2; dJ393P12.2
Summary: This gene encodes a member of the Wiskott-Aldrich syndrome protein family. The gene product is a protein that forms a multiprotein complex that links receptor kinases and actin. Binding to actin occurs through a C-terminal verprolin homology domain in all family members. The multiprotein complex serves to tranduce signals that involve changes in cell shape, motility or function. The published map location (PMID:10381382) has been changed based on recent genomic sequence comparisons, which indicate that the expressed gene is located on chromosome 1, and a pseudogene may be located on chromosome X. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]
Expression: Ubiquitous expression in esophagus (RPKM 43.4), ovary (RPKM 33.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.11

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (27404230..27490167, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (27245554..27331475, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (27730734..27816678, complement)

Chromosome 1 - NC_000001.11 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 WAVE2/miR-29/Integrin-beta1 Oncogenic Signaling Axis Promotes Tumor Growth and Metastasis in Triple-negative Breast Cancer.
Title: The WAVE2/miR-29/Integrin-β1 Oncogenic Signaling Axis Promotes Tumor Growth and Metastasis in Triple-negative Breast Cancer.
Hypomethylation-mediated upregulation of the WASF2 promoter region correlates with poor clinical outcomes in hepatocellular carcinoma.
Title: Hypomethylation-mediated upregulation of the WASF2 promoter region correlates with poor clinical outcomes in hepatocellular carcinoma.
WAVE1 and WAVE2 have distinct and overlapping roles in controlling actin assembly at the leading edge.
Title: WAVE1 and WAVE2 have distinct and overlapping roles in controlling actin assembly at the leading edge.
MicroRNA-1253 Regulation of WASF2 (WAVE2) and its Relevance to Racial Health Disparities.
Title: MicroRNA-1253 Regulation of WASF2 (WAVE2) and its Relevance to Racial Health Disparities.
High WAVE2 expression in pancreatic cancer tissues was correlated with overall survival. WAVE2 accumulated in the cell protrusions of pancreatic cancer cell lines through ACTN4 recruitment to filamentous actin in the protrusions and the activation of p27, resulting in an increase in motility and invasiveness of pancreatic ductal adenocarcinoma cells.
Title: WAVE2 is associated with poor prognosis in pancreatic cancers and promotes cell motility and invasiveness via binding to ACTN4.
Results show that in cisplatin-resistant cervical cancer tissues, Rac1, and Wave2 mRNA expression was significantly up-regulated compared to that of the cisplatin-sensitive cervical cancer tissues. In HeLa and Caski cervical cancer cell lines, Rac1 activity and Wave2 protein expression was significantly promoted by SH3BP1 overexpression.
Title: SH3BP1-induced Rac-Wave2 pathway activation regulates cervical cancer cell migration, invasion, and chemoresistance to cisplatin.
Studied leucine rich repeat kinase 2 (LRRK2)-WAS protein family member 2 (WAVE2) pathway in modulation of phagocytosis in leukocytes, as well as its possible role for altered immune function in Parkinson's Disease.
Title: Regulation of myeloid cell phagocytosis by LRRK2 via WAVE2 complex stabilization is altered in Parkinson's disease.
The level of WASF2 in gastric cancer tissues was negatively correlated with miR-146a expression and had inverse clinicopathologic features. The newly identified miR-146a/WASF2 axis may provide a novel therapeutic target for gastric cancer.
Title: Clinicopathological significance of the microRNA-146a/WASP-family verprolin-homologous protein-2 axis in gastric cancer.
These findings indicate that inhibition of the Rac1WAVE2Arp2/3 signaling pathway may promote radiosensitivity, which may partially result from the downregulation of CFL1 in U251 human glioma cells.
Title: Inhibition of the Rac1-WAVE2-Arp2/3 signaling pathway promotes radiosensitivity via downregulation of cofilin-1 in U251 human glioma cells.
SH3BP1 promoted VEGF secretion via Rac1-WAVE2 signaling, so as to exert an augmentation on cell invasion and microvessel formation.
Title: SH3-domain binding protein 1 in the tumor microenvironment promotes hepatocellular carcinoma metastasis through WAVE2 pathway.

Submit: New GeneRIF Correction See all GeneRIFs (50)

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
TSPYL5 SNPs: association with plasma estradiol concentrations and aromatase expression. 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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Replication interactions

Interaction	Pubs
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of WASF2	PubMed
HIV-1 VLP production/release from Jurkat T lymphocytes requires an intact RAC1-WASF2-BAIAP2-ARP3 pathway as demonstrated by siRNA knockdown experiments	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120-mediated phosphorylation of WAVE2 requires both G(alpha)i-dependent and -independent pathways, and is conserved both in X4 and R5 viral infection of resting CD4 T cells and primary macrophages	PubMed
	env	HIV-1 triggers WAVE2 phosphorylation at serine 351 through HIV-1 gp120 binding to the chemokine coreceptor CXCR4 or CCR5 during entry	PubMed
	env	Downregulation of the Wave2 signaling complex (Tiam-1, Abl, Rac, IRSp53, Wave2, and Arp3) with siRNA reduces HIV-1 Env-mediated cell-cell fusion and virus-cell fusion	PubMed
Nef	nef	HIV-1-mediated effects on podosomes and migration involve Nef-HCK interaction, and HCK-mediated phosphorylation of WASP at podosomes	PubMed
Pr55(Gag)	gag	HIV-1 Gag intracellular localization is modulated by WASF2 and BAIAP2 as demonstrated by double siRNA knockdowns of these cellular proteins (in Jurkat T cells)	PubMed
	gag	HIV-1 Gag is required by RAC1-WASF2-BAIAP2-ARP3 pathway for HIV VLP production/release from Jurkat T lymphocytes	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

G06203 (e-PCR)
- UniSTS:19472

AL023620 (e-PCR)
- UniSTS:31307

RH68756 (e-PCR)
- UniSTS:13967

WASF2 (e-PCR)
- UniSTS:279261

D20S1108 (e-PCR)
- UniSTS:11742

WASF2_2055 (e-PCR)
- UniSTS:281078

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables Arp2/3 complex binding	IBA Inferred from Biological aspect of Ancestor more info
enables SH3 domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables actin binding	IEA Inferred from Electronic Annotation more info
enables cadherin binding	HDA more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase A binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase A regulatory subunit binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in Rac protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in actin cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in actin filament-based movement	IEA Inferred from Electronic Annotation more info
involved_in adenylate cyclase-modulating G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in ameboidal-type cell migration	IEA Inferred from Electronic Annotation more info
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in endocytosis	IEA Inferred from Electronic Annotation more info
involved_in lamellipodium assembly	IEA Inferred from Electronic Annotation more info
involved_in lamellipodium morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in megakaryocyte development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of stress fiber assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of Arp2/3 complex-mediated actin nucleation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of lamellipodium assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in postsynaptic actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of SCAR complex	IBA Inferred from Biological aspect of Ancestor more info
part_of SCAR complex	IDA Inferred from Direct Assay more info	PubMed
part_of SCAR complex	IMP Inferred from Mutant Phenotype more info	PubMed
located_in actin cytoskeleton	TAS Traceable Author Statement more info	PubMed
located_in basolateral plasma membrane	IEA Inferred from Electronic Annotation more info
located_in cell-cell junction	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in early endosome	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
is_active_in lamellipodium	IBA Inferred from Biological aspect of Ancestor more info
located_in lamellipodium	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in ruffle	IEA Inferred from Electronic Annotation more info
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: actin-binding protein WASF2

Names: WAS protein family member 2; WASP family Verprolin-homologous protein 2; WASP family protein member 2; WASP family protein member 4; protein WAVE-2; putative Wiskott-Aldrich syndrome protein family member 4; suppressor of cyclic-AMP receptor (WASP-family); verprolin homology domain-containing protein 2; wiskott-Aldrich syndrome protein family member 2

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_001201404.3 → NP_001188333.1 actin-binding protein WASF2 isoform 2

See identical proteins and their annotated locations for NP_001188333.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate exon compared to variant 1, that causes a frameshift. The resulting isoform (2) has a shorter and distinct C-terminus compared to isoform 1.

Source sequence(s)

AA736923, AK303011, FO393419, HY001891

Consensus CDS

CCDS55582.1

UniProtKB/Swiss-Prot

Q9Y6W5

Related

ENSP00000439883.1, ENST00000536657.1
NM_006990.5 → NP_008921.1 actin-binding protein WASF2 isoform 1

See identical proteins and their annotated locations for NP_008921.1

Status: REVIEWED

Description

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

Source sequence(s)

AA736923, BC040943, DC300388, FO393419

Consensus CDS

CCDS304.1

UniProtKB/Swiss-Prot

B4DZN0, O60794, Q9UDY7, Q9Y6W5

Related

ENSP00000483313.1, ENST00000618852.5

Conserved Domains (2) summary

cd21762
Location:450 → 453

WH2; actin-binding sequence [structural motif]

cl41728
Location:428 → 479

WH2; Wiskott-Aldrich Syndrome Homology (WASP) region 2 (WH2 motif), and similar proteins