Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
The Database for Annotation, Visualization and Integrated Discovery
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DAVID Functional Annotation Table
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WAS protein family member 1(WASF1) WAS protein family member 1(WASF1) Related Genes Homo sapiens
CHROMOSOME 6,
CYTOBAND 6q21-q22,
ENSEMBL_GENE_ID ENSG00000112290,
GENERIF_SUMMARY Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck, Results suggest that recruitment of factors by Wiskott-Aldrich Syndrome protein (WASP) and Scar1 stimulates cellular actin-based motility and actin nucleation with the Arp2/3 complex., WAVE1 may act as a scaffold to recruit the NADPH oxidase to a complex involved with both cytoskeletal regulation and downstream JNK activation, the 3 WAVE isoforms exhibit common and distinct features and may potentially be involved in the regulation of actin cytoskeleton in platelets, Dictyostelium discoideum has been used to remove genetically SCAR complex members to ascertain their specific roles., WAVE-1 expression was associated with megakaryocytic differentiation; WAVE-1 and WAVE-2 moved from a detergent-soluble cytosolic fraction to insoluble cytoskeleton fraction after platelet aggregation, NESH (Abi-3), like Abi-1 and Abi-2, is a component of the Abi/WAVE complex, but likely plays a different role in the regulation of c-Abl., the Hem-1/Nap1 component of the Scar/WAVE complex localizes to propagating waves that appear to organize the leading edge of a motile neutrophil, WAVE1 is critical for formation of oligodendrocyte lamellae and myelin sheaths--REVIEW, WAVE1 is involved in multi-drug resistance through regulation the level of mdrl and Bcl-2., WAVE1 dephosphorylation and activation are likely associated with mitochondrial redistribution and dendritic spine morphogenesis., Results suggest that WAVE and the Arp2/3 complex jointly orchestrate different types of actin-based plasma membrane protrusions by promoting ruffling and inhibiting mDia2-induced filopodia., The WAVE1 expression increased in children with ALL. WAVE1 may be related to the development of ALL and may be severed as a marker for the evaluation of the severity of ALL in children., Dimerization act in hierarchical fashion, enabling WASP/WAVE proteins to integrate different classes of inputs to produce a wide range of cellular actin responses in Wiskoo Aldrich syndrome., WAVE1 and p22phox expression in PBMCs increased and was associated with the disease course in children with acute lymphocytic leukemia (ALL)., WAVE accumulation may be involved in Abeta/amyloid precursor protein mediated-tangle modification, CIP4 is a new ArgBP2 interacting protein that modulates the ArgBP2 mediated control of WAVE1 phosphorylation and cancer cell migration., WAVE1 might be involved in the migration and invasion of K562 cells through regulation of the expression level of MMP-2., WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells., Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex, Higher levels of WAVE1 in the bone marrow indicate an unfavorable prognosis in children with AML., Arf GTPases may be central components in WAVE signalling, acting directly, alongside Rac1., mDia1 and WAVE2 are important Src homology 3 domain partners of IRSp53 in forming filopodia., Study finds that WAVE1 overexpression is associated with an unfavorable prognosis. WAVE1 is an independent prognostic factor for EOC, which suggests that it is a novel and crucial predictor for EOC metastasis., Scar/WAVE regulatory complex and N-WASP play opposing roles in 3D epithelial cell migration, mRNAs encoding structural and regulatory components of the WAVE complex are localized to the leading edge of the cell, suggesting that localized protein synthesis plays a pivotal role in controlling cell spreading and migration., WAVE1 might promote the proliferative and invasive malignant behaviors through the activation of the PI3K/AKT and p38MAPK signaling pathways in epithelial ovarian cancer., D620N mutation in VPS35 restricts WASH complex recruitment to endosomes, and reveals a novel role for the WASH complex in autophagosome formation., The WAVE complex is the main activator of the Arp2/3 complex for actin filament nucleation and assembly in the lamellipodia of moving cells., WAVE1 has unique activities independent of Arp2/3 complex that can govern both the growth rates and architectures of actin filament networks. Elongation inhibitory effects of WAVE1 were mapped to its WH2 ("V") domain., a role for ARF6 in linking EGF-receptor signaling to Rac1 recruitment and activation at the plasma membrane to promote breast cancer cell directed migration, we propose that WASF1 status defines a subtype of androgen deprivation therapy -resistant prostate cancer patients, A decrease in amounts of WASF1 mRNA was also observed in human Alzheimer's disease brains, suggesting clinical relevance of the negative feedback circuit involved in homeostatic regulation of Abeta production,
SP_COMMENT domain:Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain., function:Downstream effector molecules involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton., similarity:Belongs to the SCAR/WAVE family., similarity:Contains 1 WH2 domain., subcellular location:Dot-like pattern in the cytoplasm. Concentrated in Rac-regulated membrane-ruffling areas., subunit:Component of the WAVE1 complex composed of ABI2, CYFIP2, C3orf10/HSPC300, NCKAP1 and WASF1/WAVE1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1. The complex can also be activated by NCK1 (By similarity). Binds actin and the Arp2/3 complex. Interacts with BAIAP2., tissue specificity:Highly expressed in brain. Lowly expressed in testis, ovary, colon, kidney, pancreas, thymus, small intestine and peripheral blood.,
WAS protein family member 2(WASF2) WAS protein family member 2(WASF2) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 1p36.11-p34.3,
ENSEMBL_GENE_ID ENSG00000158195,
ENTREZ_GENE_ID 10163,
GENERIF_SUMMARY The WAVE2-Abi1-Nap1-PIR121 complex is as active as the WAVE2-Abi1 sub-complex in stimulating Arp2/3, and after Rac activation it is re-localized to the leading edge of ruffles in vivo., reconstitution of the Wave-2 complex and a study of the molecular architecture, Results suggest that phosphatidylinositol (3,4,5)-triphosphate recruits WAVE2 to the polarized membrane and that this recruitment is essential for lamellipodium formation at the leading edge., the 3 WAVE isoforms exhibit common and distinct features and may potentially be involved in the regulation of actin cytoskeleton in platelets, Abi-1-mediated coupling of Abl to WAVE2 promotes Abl-evoked WAVE2 tyrosine phosphorylation required to link WAVE2 with activated Rac and with actin polymerization and remodeling at the cell periphery., WAVE-2 and WAVE-3 expression was not changed by the megakaryocytic differentiation; WAVE-1 and WAVE-2 moved from a detergent-soluble cytosolic fraction to insoluble cytoskeleton fraction after platelet aggregation, WAVE2 is a key component of the actin regulatory machinery in T cells and that it also participates in linking intracellular calcium store depletion to calcium release-activated calcium (CRAC) channel activation., Coexpression of Arp2 and WAVE2 is correlated with poorer patient outcome., Therefore, IRSp53 optimizes the activity of the WAVE2 complex in the presence of activated Rac and PIP(3)., c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo; Abi-1 forms the crucial link between these two factors, WAVE2 expression is elevated in HCC tissues, which correlates with a poor prognosis, suggesting WAVE2 as a candidate prognostic marker of HCC., Colocalization of Arp2 and WAVE2 is an independent risk factor for liver metastasis of colorectal carcinoma., Data show that Chlamydia trachomatis activates Rac and promotes its interaction with WAVE2 and Abi-1 to activate the Arp2/3 complex resulting in the induction of actin cytoskeletal rearrangements that are required for invasion., Results decribe a mechanism in which signals from the T cell receptor produce WAVE2-ARP2/3-mediated de novo actin polymerization, leading to integrin clustering and high-affinity binding through the recruitment of vinculin and talin., Over-expression of WAVE2 is seen in node-positive cases as well as in moderately and poorly differentiated breast cancers., Data suggest that the promotion of lamellipodia formation by HGF in MDA-MB-231 cells is Rac1-dependent and requires KIF5B-mediated transport of WAVE2 and IQGAP1 to the cell periphery along microtubules., results suggest that long protrusions formed in a WAVE2- and microtubule-dependent manner may identify the cells at the later stage of invasion, possibly after the formation of invadopodia in the 3-D cultures, Results identify a mechanism by which the WAVE2 complex regulates T cell receptor signaling to Rap1 and integrin activation via Abl- and CrkL-C3G., Phosphorylation of all five sites on endogenous WAVE2 and their mutation to non-phosphorylatable alanine residues leads to inhibition of WAVE2 function in vivo, was demonstrated., Pak1 protein binds to WASF2 protein and is transported with WASF2 protein to the leading edge by stimulation with hepatocyte growth factor., betaPIX and GIT1 regulate the hepatocyte growth factor-induced and Rac1-dependent membrane transport of WAVE2 and consequently, lamellipodia formation., HSPC300 is associated with metastatic potential of lung squamous cell carcinoma through its interaction with WAVE2, Data show that activation of the WAVE2 complex requires simultaneous interactions with prenylated Rac-GTP and acidic phospholipids, as well as a specific state of phosphorylation., WAVE2-membrane targeting is directionally controlled by binding of the EB1-stathmin complex to WAVE2-bearing microtubules and by the interaction between WAVE2 and PIP3 produced near IGF-IR that is locally activated by IGF-I., WAVE2 complexs with insulin receptor substrate p53 and is crucial for membrane targeting followed by local accumulation of WAVE2 at the leading edge of cells., WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation, MYH9 is required for lamellipodia formation since it provides contractile forces and tension for the F-actin network to form convex arcs at the leading edge through constitutive binding to WAVE2 and colocalization with PIP(3) in response to IGF-I., WAVE2 and WASp define parallel pathways to F-actin reorganization and function in NK cells; although WAVE2 was not required for NK cell innate function, it was accessible through adaptive immunity via IL-2., Data suggest that ERK coordinates adhesion disassembly with WAVE2 regulatory complex activation and actin polymerization to promote productive leading edge advancement during cell migration., results indicate that by mediating intensive F-actin accumulation at the sites of cell infiltration, WAVE2, N-WASP, and Mena are crucial for PI3K-dependent cell invasion induced by PDGF, We demonstrate that WAVE2-Arp2/3 is a major nucleator of actin assembly at the zonula adherens and likely acts in response to junctional Rac signaling, results suggest that SKAP2 negatively regulates cell migration and tumor invasion in fibroblasts and glioblastoma cells by suppressing actin assembly induced by the WAVE2-cortactin complex, Identification of an onco-suppressive role of miR-146a in gastric cancer cells by its reduction of WASF2 expression., data reveal a critical role for WAVE2 complex in regulation of cellular signaling and epithelial morphogenesis, Decreased expression of Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 may be involved in the development of pre-eclampsia., these results suggest that Arp2/3 and the upstream regulator, WAVE2, are essential co-factors hijacked by HIV for intracellular migration, and may serve as novel targets to prevent HIV transmission., Cortactin has a role as a scaffold for Arp2/3 and WAVE2 at the epithelial zonula adherens, WAVE2 is down-regulated in gastric cancer, WASp and WAVE2 differ in their dynamics and their associated proteins, the MCP1-induced cortactin phosphorylation is dependent on PLCb3-mediated PKC activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2,
SP_COMMENT domain:Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain., function:Downstream effector molecules involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton., similarity:Belongs to the SCAR/WAVE family., similarity:Contains 1 WH2 domain., subcellular location:At the interface between the lamellipodial actin meshwork and the membrane., subunit:Binds actin and the Arp2/3 complex. Interacts with BAIAP2. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 and WASF2/WAVE2. Directly interacts with C3orf10/HSPC300., tissue specificity:Expressed in all tissues with strongest expression in placenta, lung, and peripheral blood leukocytes, but not in skeletal muscle.,
WAS protein family member 3(WASF3) WAS protein family member 3(WASF3) Related Genes Homo sapiens
CHROMOSOME 13,
CYTOBAND 13q12,
ENSEMBL_GENE_ID ENSG00000132970,
ENTREZ_GENE_ID 10810,
GENERIF_SUMMARY patient with ganglioneuroblastoma carries an apparently balanced t(1, the 3 WAVE isoforms exhibit common and distinct features and may potentially be involved in the regulation of actin cytoskeleton in platelets, during megakaryocytic differentiation, platelets expressed WAVE-1 and WAVE-2, whereas WAVE-3 expression was hardly to be detected. WAVE-3 expression was not changed by the differentiation, all three Scar/WAVE isoforms behave similarly and are likely to participate in the same kinds of protein complexes that regulate actin assembly, WAVE3-mediated migration in MDA-MB-231 cells via lamellipodia formation is activated downstream of PI3K and induced by PDGF, The WAVE3 is a member of the WASP/WAVE family of proteins, which play a critical role in the regulation of actin polymerization, cytoskeleton organization, and cell motility., the activation of WAVE3 to promote actin remodeling is enhanced by the c-Abl-mediated tyrosine phosphorylation of WAVE3., WAVE3 is pivotal in controlling the invasiveness of prostate cancer cells., Studies identified a novel mechanism for the regulation of WAVE3 expression in cancer cells, which controls the invasive properties and morphology of cancer cells associated with their metastatic potential., The study also identifies a critical role for WAVE3, downstream of miR-31, in the invasion-metastasis cascade., coordinated expression patterns of the WASF3 metastasis promoter gene and the KISS1 metastasis suppressor gene appear to exert their influence through inhibition of NF-kappaB signaling, which in turn regulates MMP-9 production facilitating invasion., HSP90 and HSP70 proteins are essential for stabilization and activation of WASF3 metastasis-promoting protein., demonstrate WASF3 is a HIF1A-regulated gene and suggests a mechanism to explain the observation of elevated expression of WASF3 in advanced stage tumors, MMP-9 and WAVE3 were over-expressed in colorectal cancer tissues compared with normal mucosa., WAVE3-depleted breast cancer cells move more slowly but more persistently on a 2-dimensional matrix. They typically only show one lamellipod. WAVE3 appears to have no role in driving invasiveness. Lamellipodial persistence is not crucial in 3-dimensions., increased expression levels of WAVE3 are associated with the progression and metastasis of triple negative breast cancer, ZEB1/2 upregulation by WASF3 results from downregulation of KISS1, leading to the release of inhibition of nuclear factor (NF)kappaB by IkappaBalpha, these results define a novel signaling network whereby JAK2/STAT3 signaling creates a feed-forward loop to raise activated WASF3 levels that promote cancer cell motility., Upregulated WAVE3 expression is essential for TGF-beta-mediated EMT and metastasis of triple-negative breast cancer cells., miR-217 functions as a tumor-suppressive miRNA and inhibits the osteosarcoma tumorigenesis through targeting WASF3., We show that WAVE3-mediated modulation of NFkappaB is required for invadopodia formation as well as MMP9 expression and activity that are needed for cancer cells to degrade the ECM, WAVE3 promotes epithelial-mesenchymal transition of gastric cancer through upregulation of Snail., WAVE3 is pivotal in controlling oncogenic phenotypes of human hepatocellular carcinoma cells., stabilization of WASF3 function occurs through its interaction with ATAD3A and GRP78, which may provide a bridge between the ER and mitochondria, allowing communication between the two organelles,
SP_COMMENT domain:Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain., function:Downstream effector molecules involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton., similarity:Belongs to the SCAR/WAVE family., similarity:Contains 1 WH2 domain., subunit:Binds actin and the Arp2/3 complex., tissue specificity:Expressed in ovary and brain.,