Wiskott-Aldrich syndrome protein

Details

Name
Wiskott-Aldrich syndrome protein
Synonyms
  • IMD2
  • WASp
Gene Name
WAS
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004935|Wiskott-Aldrich syndrome protein
MSGGPMGGRPGGRGAPAVQQNIPSTLLQDHENQRLFEMLGRKCLTLATAVVQLYLALPPG
AEHWTKEHCGAVCFVKDNPQKSYFIRLYGLQAGRLLWEQELYSQLVYSTPTPFFHTFAGD
DCQAGLNFADEDEAQAFRALVQEKIQKRNQRQSGDRRQLPPPPTPANEERRGGLPPLPLH
PGGDQGGPPVGPLSLGLATVDIQNPDITSSRYRGLPAPGPSPADKKRSGKKKISKADIGA
PSGFKHVSHVGWDPQNGFDVNNLDPDLRSLFSRAGISEAQLTDAETSKLIYDFIEDQGGL
EAVRQEMRRQEPLPPPPPPSRGGNQLPRPPIVGGNKGRSGPLPPVPLGIAPPPPTPRGPP
PPGRGGPPPPPPPATGRSGPLPPPPPGAGGPPMPPPPPPPPPPPSSGNGPAPPPLPPALV
PAGGLAPGGGRGALLDQIRQGIQLNKTPGAPESSALQPPPQSSEGLVGALMHVMQKRSRA
IHSSDEGEDQAGDEDEDDEWDD
Number of residues
502
Molecular Weight
52912.175
Theoretical pI
6.61
GO Classification
Functions
GTPase regulator activity / identical protein binding / phospholipase binding / protein kinase binding / SH3 domain binding
Processes
actin filament polymerization / actin filament-based movement / actin polymerization or depolymerization / blood coagulation / defense response / endosomal transport / epidermis development / Fc-gamma receptor signaling pathway involved in phagocytosis / immune response / innate immune response / negative regulation of cell motility / positive regulation of Arp2/3 complex-mediated actin nucleation / protein complex assembly / regulation of catalytic activity / regulation of T cell antigen processing and presentation / small GTPase mediated signal transduction / T cell activation / T cell receptor signaling pathway
Components
actin cytoskeleton / cell-cell junction / cytosol / extracellular exosome / vesicle membrane
General Function
Sh3 domain binding
Specific Function
Effector protein for Rho-type GTPases. Regulates actin filament reorganization via its interaction with the Arp2/3 complex. Important for efficient actin polymerization. Possible regulator of lymphocyte and platelet function. Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021676|Wiskott-Aldrich syndrome protein (WAS)
ATGAGTGGGGGCCCAATGGGAGGAAGGCCCGGGGGCCGAGGAGCACCAGCGGTTCAGCAG
AACATACCCTCCACCCTCCTCCAGGACCACGAGAACCAGCGACTCTTTGAGATGCTTGGA
CGAAAATGCTTGACGCTGGCCACTGCAGTTGTTCAGCTGTACCTGGCGCTGCCCCCTGGA
GCTGAGCACTGGACCAAGGAGCATTGTGGGGCTGTGTGCTTCGTGAAGGATAACCCCCAG
AAGTCCTACTTCATCCGCCTTTACGGCCTTCAGGCTGGTCGGCTGCTCTGGGAACAGGAG
CTGTACTCACAGCTTGTCTACTCCACCCCCACCCCCTTCTTCCACACCTTCGCTGGAGAT
GACTGCCAAGCGGGGCTGAACTTTGCAGACGAGGACGAGGCCCAGGCCTTCCGGGCCCTC
GTGCAGGAGAAGATACAAAAAAGGAATCAGAGGCAAAGTGGAGACAGACGCCAGCTACCC
CCACCACCAACACCAGCCAATGAAGAGAGAAGAGGAGGGCTCCCACCCCTGCCCCTGCAT
CCAGGTGGAGACCAAGGAGGCCCTCCAGTGGGTCCGCTCTCCCTGGGGCTGGCGACAGTG
GACATCCAGAACCCTGACATCACGAGTTCACGATACCGTGGGCTCCCAGCACCTGGACCT
AGCCCAGCTGATAAGAAACGCTCAGGGAAGAAGAAGATCAGCAAAGCTGATATTGGTGCA
CCCAGTGGATTCAAGCATGTCAGCCACGTGGGGTGGGACCCCCAGAATGGATTTGACGTG
AACAACCTCGACCCAGATCTGCGGAGTCTGTTCTCCAGGGCAGGAATCAGCGAGGCCCAG
CTCACCGACGCCGAGACCTCTAAACTTATCTACGACTTCATTGAGGACCAGGGTGGGCTG
GAGGCTGTGCGGCAGGAGATGAGGCGCCAGGAGCCACTTCCGCCGCCCCCACCGCCATCT
CGAGGAGGGAACCAGCTCCCCCGGCCCCCTATTGTGGGGGGTAACAAGGGTCGTTCTGGT
CCACTGCCCCCTGTACCTTTGGGGATTGCCCCACCCCCACCAACACCCCGGGGACCCCCA
CCCCCAGGCCGAGGGGGCCCTCCACCACCACCCCCTCCAGCTACTGGACGTTCTGGACCA
CTGCCCCCTCCACCCCCTGGAGCTGGTGGGCCACCCATGCCACCACCACCGCCACCACCG
CCACCGCCGCCCAGCTCCGGGAATGGACCAGCCCCTCCCCCACTCCCTCCTGCTCTGGTG
CCTGCCGGGGGCCTGGCCCCTGGTGGGGGTCGGGGAGCGCTTTTGGATCAAATCCGGCAG
GGAATTCAGCTGAACAAGACCCCTGGGGCCCCAGAGAGCTCAGCGCTGCAGCCACCACCT
CAGAGCTCAGAGGGACTGGTGGGGGCCCTGATGCACGTGATGCAGAAGAGAAGCAGAGCC
ATCCACTCCTCCGACGAAGGGGAGGACCAGGCTGGCGATGAAGATGAAGATGATGAATGG
GATGACTGA
Chromosome Location
X
Locus
Xp11.4-p11.21
External Identifiers
ResourceLink
UniProtKB IDP42768
UniProtKB Entry NameWASP_HUMAN
GenBank Gene IDU12707
GenAtlas IDWAS
HGNC IDHGNC:12731
General References
  1. Derry JM, Ochs HD, Francke U: Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell. 1994 Aug 26;78(4):635-44. [PubMed:8069912]
  2. Derry JM, Ochs HD, Francke U: Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell. 1994 Dec 2;79(5):following 922. [PubMed:8001129]
  3. Kwan SP, Hagemann TL, Radtke BE, Blaese RM, Rosen FS: Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene. Proc Natl Acad Sci U S A. 1995 May 9;92(10):4706-10. [PubMed:7753869]
  4. Hagemann TL, Kwan SP: The identification and characterization of two promoters and the complete genomic sequence for the Wiskott-Aldrich syndrome gene. Biochem Biophys Res Commun. 1999 Mar 5;256(1):104-9. [PubMed:10066431]
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  8. Kolluri R, Tolias KF, Carpenter CL, Rosen FS, Kirchhausen T: Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5615-8. [PubMed:8643625]
  9. Ramesh N, Anton IM, Hartwig JH, Geha RS: WIP, a protein associated with wiskott-aldrich syndrome protein, induces actin polymerization and redistribution in lymphoid cells. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14671-6. [PubMed:9405671]
  10. Cory GO, Garg R, Cramer R, Ridley AJ: Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein. J Biol Chem. 2002 Nov 22;277(47):45115-21. Epub 2002 Sep 15. [PubMed:12235133]
  11. Cory GO, Cramer R, Blanchoin L, Ridley AJ: Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP. Mol Cell. 2003 May;11(5):1229-39. [PubMed:12769847]
  12. Badour K, Zhang J, Shi F, Leng Y, Collins M, Siminovitch KA: Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein (WASp) tyrosine phosphorylation is required for coupling T cell antigen receptor engagement to WASp effector function and T cell activation. J Exp Med. 2004 Jan 5;199(1):99-112. [PubMed:14707117]
  13. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ: Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol. 2005 Jan;23(1):94-101. Epub 2004 Dec 12. [PubMed:15592455]
  14. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [PubMed:18088087]
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  17. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
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  20. Kim AS, Kakalis LT, Abdul-Manan N, Liu GA, Rosen MK: Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome protein. Nature. 2000 Mar 9;404(6774):151-8. [PubMed:10724160]
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  22. Chereau D, Kerff F, Graceffa P, Grabarek Z, Langsetmo K, Dominguez R: Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16644-9. Epub 2005 Nov 7. [PubMed:16275905]
  23. St-Jean M, Izard T, Sygusch J: A hydrophobic pocket in the active site of glycolytic aldolase mediates interactions with Wiskott-Aldrich syndrome protein. J Biol Chem. 2007 May 11;282(19):14309-15. Epub 2007 Feb 27. [PubMed:17329259]
  24. Cheng HC, Skehan BM, Campellone KG, Leong JM, Rosen MK: Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U). Nature. 2008 Aug 21;454(7207):1009-13. doi: 10.1038/nature07160. Epub 2008 Jul 23. [PubMed:18650809]
  25. Kolluri R, Shehabeldin A, Peacocke M, Lamhonwah AM, Teichert-Kuliszewska K, Weissman SM, Siminovitch KA: Identification of WASP mutations in patients with Wiskott-Aldrich syndrome and isolated thrombocytopenia reveals allelic heterogeneity at the WAS locus. Hum Mol Genet. 1995 Jul;4(7):1119-26. [PubMed:8528198]
  26. Derry JM, Kerns JA, Weinberg KI, Ochs HD, Volpini V, Estivill X, Walker AP, Francke U: WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia. Hum Mol Genet. 1995 Jul;4(7):1127-35. [PubMed:8528199]
  27. Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, Strina D, Patrosso MC, Ramenghi U, Sacco MG, et al.: X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene. Nat Genet. 1995 Apr;9(4):414-7. [PubMed:7795648]
  28. Schindelhauer D, Weiss M, Hellebrand H, Golla A, Hergersberg M, Seger R, Belohradsky BH, Meindl A: Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product. Hum Genet. 1996 Jul;98(1):68-76. [PubMed:8682510]
  29. Remold-O'Donnell E, Cooley J, Shcherbina A, Hagemann TL, Kwan SP, Kenney DM, Rosen FS: Variable expression of WASP in B cell lines of Wiskott-Aldrich syndrome patients. J Immunol. 1997 May 1;158(9):4021-5. [PubMed:9126958]
  30. Ariga T, Yamada M, Sakiyama Y: Mutation analysis of five Japanese families with Wiskott-Aldrich syndrome and determination of the family members' carrier status using three different methods. Pediatr Res. 1997 Apr;41(4 Pt 1):535-40. [PubMed:9098856]
  31. MacCarthy-Morrogh L, Gaspar HB, Wang YC, Katz F, Thompson L, Layton M, Jones AM, Kinnon C: Absence of expression of the Wiskott-Aldrich syndrome protein in peripheral blood cells of Wiskott-Aldrich syndrome patients. Clin Immunol Immunopathol. 1998 Jul;88(1):22-7. [PubMed:9683546]
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  33. Parolini O, Ressmann G, Haas OA, Pawlowsky J, Gadner H, Knapp W, Holter W: X-linked Wiskott-Aldrich syndrome in a girl. N Engl J Med. 1998 Jan 29;338(5):291-5. [PubMed:9445409]
  34. Ho LL, Ayling J, Prosser I, Kronenberg H, Iland H, Joshua D: Missense C168T in the Wiskott--Aldrich Syndrome protein gene is a common mutation in X-linked thrombocytopenia. Br J Haematol. 2001 Jan;112(1):76-80. [PubMed:11167787]
  35. Devriendt K, Kim AS, Mathijs G, Frints SG, Schwartz M, Van Den Oord JJ, Verhoef GE, Boogaerts MA, Fryns JP, You D, Rosen MK, Vandenberghe P: Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia. Nat Genet. 2001 Mar;27(3):313-7. [PubMed:11242115]
  36. Lemahieu V, Gastier JM, Francke U: Novel mutations in the Wiskott-Aldrich syndrome protein gene and their effects on transcriptional, translational, and clinical phenotypes. Hum Mutat. 1999;14(1):54-66. [PubMed:10447259]
  37. Notarangelo LD, Mazza C, Giliani S, D'Aria C, Gandellini F, Ravelli C, Locatelli MG, Nelson DL, Ochs HD, Notarangelo LD: Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia. Blood. 2002 Mar 15;99(6):2268-9. [PubMed:11877312]
  38. El-Hakeh J, Rosenzweig S, Oleastro M, Basack N, Berozdnik L, Molina F, Rivas EM, Zelazko M, Danielian S: Wiskott-Aldrich syndrome in Argentina: 17 unique, including nine novel, mutations. Hum Mutat. 2002 Feb;19(2):186-7. [PubMed:11793485]
  39. Wada T, Itoh M, Maeba H, Toma T, Niida Y, Saikawa Y, Yachie A: Intermittent X-linked thrombocytopenia with a novel WAS gene mutation. Pediatr Blood Cancer. 2014 Apr;61(4):746-8. doi: 10.1002/pbc.24787. Epub 2013 Sep 21. [PubMed:24115682]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01731(S)-wiskostatinexperimentalunknownDetails