WIPF1

WAS/WASL-interacting protein (WIP) is a protein that in humans is encoded by the WIPF1 gene.^[5][6]

WIPF1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2A41
Identifiers
Aliases	WIPF1, PRPL-2, WASPIP, WIP, WAS2, WAS/WASL interacting protein family member 1
External IDs	OMIM: 602357; MGI: 2178801; HomoloGene: 86891; GeneCards: WIPF1; OMA:WIPF1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q31.1 Start 174,559,572 bp[1] End 174,682,916 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 C3|2 43.68 cM Start 73,259,954 bp[2] End 73,360,078 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood monocyte appendix lymph node bone marrow cell trabecular bone granulocyte periodontal fiber tibia inferior ganglion of vagus nerve Top expressed in granulocyte mesenteric lymph nodes spleen blood thymus sciatic nerve aortic valve ascending aorta body of femur stroma of bone marrow More reference expression data BioGPS More reference expression data
Gene ontology Molecular function actin binding profilin binding protein binding SH3 domain binding actin filament binding Cellular component actin cytoskeleton cytoplasm cytosol cell projection ruffle cytoskeleton cytoplasmic vesicle actin filament actin cortical patch Biological process actin polymerization or depolymerization Fc-gamma receptor signaling pathway involved in phagocytosis response to other organism actin filament-based movement protein-containing complex assembly actin cortical patch assembly endocytosis positive regulation of actin nucleation actin cortical patch localization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7456 215280 Ensembl ENSG00000115935 ENSMUSG00000075284 UniProt O43516 Q8K1I7 RefSeq (mRNA) NM_001077269 NM_003387 NM_001289722 NM_001289723 NM_153138 RefSeq (protein) NP_001070737 NP_003378 NP_001362761 NP_001362762 NP_001362763 NP_001362764 NP_001362765 NP_001362766 NP_001362767 NP_001362768 NP_001276651 NP_001276652 NP_694778 Location (UCSC) Chr 2: 174.56 – 174.68 Mb Chr 2: 73.26 – 73.36 Mb PubMed search [3] [4]
Wikidata
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Function

This gene encodes a protein that plays an important role in the organization of the actin cytoskeleton. Overexpression of WIP in mammalian cells has been shown to increase actin polymerization.^[5] The encoded protein binds to a region of Wiskott–Aldrich syndrome protein that is frequently mutated in Wiskott–Aldrich syndrome, an X-linked recessive disorder. Impairment of the interaction between these two proteins may contribute to the disease. Two transcript variants encoding the same protein have been identified for this gene.^[6] In patients lacking the WIPF1 gene WASp protein levels are depleted and WAS symptoms present.^[7]

Interactions

WIP has been shown to interact with Wiskott–Aldrich syndrome protein,^[5][8] N-WASp, Cortactin,^[9] NCK1,^[8] MYO1e^[10] and ITSN1.^[11] While Wiskott–Aldrich syndrome protein (WASp)is expressed only in haematopoetic cells, WIPF1 is expressed ubiquitously.^[5] The majority of the mutations causing Wiskott Aldrich Syndrome are located in the WH1 domain of WASp.^[12] These mutations affect WASp-WIPF1 binding.^[13] WIPF1 has an N-terminal profilin binding domain, two actin binding WH2 domains, a central polyproline stretch, and a C-terminal WASp Binding Domain. WASp protein is degraded in the absence of WIP; but the ubiquitously expressed WASp ortholog N-WASp remains stable in the absence of WIP.

Work in yeast

WIPF1 functions and interactions have been studied in multiple fungal systems including Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans,^[14] and Magnaporthe grisea.^[15]

Yeast Vrp1 is recruited to sites of endocytosis by WASp homologs. Here it interacts with myosin-1 and enhances myosin-1 mediated activation of the Arp2/3 complex.^[16] In addition to a role in endocytosis, Saccharomyces cerevisiae Vrp1 functions in cytokinesis and cell polarization.^[17]

In Schizosaccharomyces pombe, Vrp1 interaction with myosin-1 is believed to help position new actin branches near the membrane, enhancing the amount of force against the membrane. This interaction is disrupted by the yeast specific protein Bbc1/Mti1/SPAC23A1.17, which competes with Vrp1 for binding the Myo1e homolog.^[18]