WIPF1
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
WAS/WASL-interacting protein (WIP) is a protein that in humans is encoded by the WIPF1 gene.[5][6]
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]