ID WASP_HUMAN Reviewed; 502 AA.
AC P42768; Q9BU11; Q9UNJ9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 24-JAN-2024, entry version 250.
DE RecName: Full=Actin nucleation-promoting factor WAS {ECO:0000305};
DE AltName: Full=Wiskott-Aldrich syndrome protein;
DE Short=WASp;
GN Name=WAS; Synonyms=IMD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=T-cell;
RX PubMed=8069912; DOI=10.1016/0092-8674(94)90528-2;
RA Derry J.M.J., Ochs H.D., Francke U.;
RT "Isolation of a novel gene mutated in Wiskott-Aldrich syndrome.";
RL Cell 78:635-644(1994).
RN [2]
RP ERRATUM OF PUBMED:8069912.
RX PubMed=8001129;
RA Derry J.M.J., Ochs H.D., Francke U.;
RL Cell 79:923-923(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS WAS TRP-43; MET-45; LEU-58;
RP LYS-133 AND THR-134.
RX PubMed=7753869; DOI=10.1073/pnas.92.10.4706;
RA Kwan S.-P., Hagemann T.L., Radtke B.E., Blaese R.M., Rosen F.S.;
RT "Identification of mutations in the Wiskott-Aldrich syndrome gene and
RT characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent
RT to the disease gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:4706-4710(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10066431; DOI=10.1006/bbrc.1999.0292;
RA Hagemann T.L., Kwan S.-P.;
RT "The identification and characterization of two promoters and the complete
RT genomic sequence for the Wiskott-Aldrich syndrome gene.";
RL Biochem. Biophys. Res. Commun. 256:104-109(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-13.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8625410; DOI=10.1016/s0092-8674(00)81050-8;
RA Symons M., Derry J.M., Karlak B., Jiang S., Lemahieu V., Mccormick F.,
RA Francke U., Abo A.;
RT "Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs,
RT is implicated in actin polymerization.";
RL Cell 84:723-734(1996).
RN [9]
RP INTERACTION WITH CDC42.
RX PubMed=8643625; DOI=10.1073/pnas.93.11.5615;
RA Kolluri R., Tolias K.F., Carpenter C.L., Rosen F.S., Kirchhausen T.;
RT "Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase
RT Cdc42.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:5615-5618(1996).
RN [10]
RP FUNCTION, AND INTERACTION WITH WIP.
RX PubMed=9405671; DOI=10.1073/pnas.94.26.14671;
RA Ramesh N., Anton I.M., Hartwig J.H., Geha R.S.;
RT "WIP, a protein associated with Wiskott-Aldrich syndrome protein, induces
RT actin polymerization and redistribution in lymphoid cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:14671-14676(1997).
RN [11]
RP FUNCTION, PHOSPHORYLATION AT TYR-291 BY HCK, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND INTERACTION WITH HCK.
RX PubMed=12235133; DOI=10.1074/jbc.m203346200;
RA Cory G.O., Garg R., Cramer R., Ridley A.J.;
RT "Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate
RT actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome
RT protein.";
RL J. Biol. Chem. 277:45115-45121(2002).
RN [12]
RP FUNCTION, PHOSPHORYLATION AT SER-483 AND SER-484, AND INTERACTION WITH THE
RP ARP2/3 COMPLEX.
RX PubMed=12769847; DOI=10.1016/s1097-2765(03)00172-2;
RA Cory G.O.C., Cramer R., Blanchoin L., Ridley A.J.;
RT "Phosphorylation of the WASP-VCA domain increases its affinity for the
RT Arp2/3 complex and enhances actin polymerization by WASP.";
RL Mol. Cell 11:1229-1239(2003).
RN [13]
RP PHOSPHORYLATION AT TYR-291 BY FYN.
RX PubMed=14707117; DOI=10.1084/jem.20030976;
RA Badour K., Zhang J., Shi F., Leng Y., Collins M., Siminovitch K.A.;
RT "Fyn and PTP-PEST-mediated regulation of Wiskott-Aldrich syndrome protein
RT (WASp) tyrosine phosphorylation is required for coupling T cell antigen
RT receptor engagement to WASp effector function and T cell activation.";
RL J. Exp. Med. 199:99-112(2004).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-291, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-291; SER-483 AND SER-484, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-291 AND SER-483, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INVOLVEMENT IN WAS.
RX PubMed=20574068; DOI=10.1126/scitranslmed.3000813;
RA Taylor M.D., Sadhukhan S., Kottangada P., Ramgopal A., Sarkar K.,
RA D'Silva S., Selvakumar A., Candotti F., Vyas Y.M.;
RT "Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in
RT human Wiskott-Aldrich syndrome.";
RL Sci. Transl. Med. 2:37RA44-37RA44(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-221, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [22]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=29925947; DOI=10.1038/s41586-018-0237-5;
RA Schrank B.R., Aparicio T., Li Y., Chang W., Chait B.T., Gundersen G.G.,
RA Gottesman M.E., Gautier J.;
RT "Nuclear ARP2/3 drives DNA break clustering for homology-directed repair.";
RL Nature 559:61-66(2018).
RN [23]
RP STRUCTURE BY NMR OF 230-288 IN COMPLEX WITH CDC42.
RX PubMed=10360578; DOI=10.1038/20726;
RA Abdul-Manan N., Aghazadeh B., Liu G.A., Majumdar A., Ouerfelli O.,
RA Siminovitch K.A., Rosen M.K.;
RT "Structure of Cdc42 in complex with the GTPase-binding domain of the
RT 'Wiskott-Aldrich syndrome' protein.";
RL Nature 399:379-383(1999).
RN [24]
RP STRUCTURE BY NMR OF 242-492, AND CONFORMATION CHANGE.
RX PubMed=10724160; DOI=10.1038/35004513;
RA Kim A.S., Kakalis L.T., Abdul-Manan N., Liu G.A., Rosen M.K.;
RT "Autoinhibition and activation mechanisms of the Wiskott-Aldrich syndrome
RT protein.";
RL Nature 404:151-158(2000).
RN [25]
RP STRUCTURE BY NMR OF 242-310 IN COMPLEX WITH WISKOSTATIN.
RX PubMed=15235593; DOI=10.1038/nsmb796;
RA Peterson J.R., Bickford L.C., Morgan D., Kim A.S., Ouerfelli O.,
RA Kirschner M.W., Rosen M.K.;
RT "Chemical inhibition of N-WASP by stabilization of a native autoinhibited
RT conformation.";
RL Nat. Struct. Mol. Biol. 11:747-755(2004).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 430-458 IN COMPLEX WITH ACTIN,
RP FUNCTION, AND SUBUNIT.
RX PubMed=16275905; DOI=10.1073/pnas.0507021102;
RA Chereau D., Kerff F., Graceffa P., Grabarek Z., Langsetmo K., Dominguez R.;
RT "Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology
RT domain 2 and the implications for filament assembly.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:16644-16649(2005).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 488-502 IN COMPLEX WITH ALDOA.
RX PubMed=17329259; DOI=10.1074/jbc.m611505200;
RA St-Jean M., Izard T., Sygusch J.;
RT "A hydrophobic pocket in the active site of glycolytic aldolase mediates
RT interactions with Wiskott-Aldrich syndrome protein.";
RL J. Biol. Chem. 282:14309-14315(2007).
RN [28]
RP STRUCTURE BY NMR OF 242-310, FUNCTION, AND INTERACTION WITH E.COLI ESPF(U).
RX PubMed=18650809; DOI=10.1038/nature07160;
RA Cheng H.C., Skehan B.M., Campellone K.G., Leong J.M., Rosen M.K.;
RT "Structural mechanism of WASP activation by the enterohaemorrhagic E. coli
RT effector EspF(U).";
RL Nature 454:1009-1013(2008).
RN [29]
RP VARIANTS WAS HIS-30 DEL; LYS-31; MET-75; PRO-82; CYS-86; HIS-86; CYS-97;
RP LYS-133 AND GLU-476.
RX PubMed=8528198; DOI=10.1093/hmg/4.7.1119;
RA Kolluri R., Shehabeldin A., Peacocke M., Lamhonwah A.-M.,
RA Teichert-Kuliszewska K., Weissman S.M., Siminovitch K.A.;
RT "Identification of WASP mutations in patients with Wiskott-Aldrich syndrome
RT and isolated thrombocytopenia reveals allelic heterogeneity at the WAS
RT locus.";
RL Hum. Mol. Genet. 4:1119-1126(1995).
RN [30]
RP VARIANTS THC1 PHE-27; ILE-48 AND LYS-477, AND VARIANTS WAS MET-75; LEU-86;
RP HIS-86; LYS-131 AND CYS-187.
RX PubMed=8528199; DOI=10.1093/hmg/4.7.1127;
RA Derry J.M.J., Kerns J.A., Weinberg K.I., Ochs H.D., Volpini V.,
RA Estivill X., Walker A.P., Francke U.;
RT "WASP gene mutations in Wiskott-Aldrich syndrome and X-linked
RT thrombocytopenia.";
RL Hum. Mol. Genet. 4:1127-1135(1995).
RN [31]
RP VARIANTS THC1 VAL-56 AND GLU-236.
RX PubMed=7795648; DOI=10.1038/ng0495-414;
RA Villa A., Notarangelo L., Macchi P., Mantuano E., Cavagni G., Brugnoni D.,
RA Strina D., Patrosso M.C., Ramenghi U., Sacco M.G., Ugazio A., Vezzoni P.;
RT "X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic
RT diseases with mutations in the WASP gene.";
RL Nat. Genet. 9:414-417(1995).
RN [32]
RP VARIANT WAS HIS-86.
RX PubMed=8682510; DOI=10.1007/s004390050162;
RA Schindelhauer D., Weiss M., Hellebrand H., Golla A., Hergersberg M.,
RA Seger R., Belohradsky B.H., Meindl A.;
RT "Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but
RT clustering of missense mutations in the amino-terminal part of the WASP
RT gene product.";
RL Hum. Genet. 98:68-76(1996).
RN [33]
RP VARIANTS WAS TRP-43; MET-45; MET-75 AND CYS-86.
RX PubMed=9126958;
RA Remold-O'Donnell E., Cooley J., Shcherbina A., Hagemann T.L., Kwan S.-P.,
RA Kenney D.M., Rosen F.S.;
RT "Variable expression of WASP in B cell lines of Wiskott-Aldrich syndrome
RT patients.";
RL J. Immunol. 158:4021-4025(1997).
RN [34]
RP VARIANTS WAS LYS-31 AND MET-45.
RX PubMed=9098856; DOI=10.1203/00006450-199704000-00013;
RA Ariga T., Yamada M., Sakiyama Y.;
RT "Mutation analysis of five Japanese families with Wiskott-Aldrich syndrome
RT and determination of the family members' carrier status using three
RT different methods.";
RL Pediatr. Res. 41:535-540(1997).
RN [35]
RP VARIANTS WAS MET-75; LEU-84; ASP-89 AND LYS-133.
RX PubMed=9683546; DOI=10.1006/clin.1998.4557;
RA MacCarthy-Morrogh L., Gaspar H.B., Wang Y.-C., Katz F., Thompson L.,
RA Layton M., Jones A.M., Kinnon C.;
RT "Absence of expression of the Wiskott-Aldrich syndrome protein in
RT peripheral blood cells of Wiskott-Aldrich syndrome patients.";
RL Clin. Immunol. Immunopathol. 88:22-27(1998).
RN [36]
RP VARIANT WAS VAL-56.
RX PubMed=9713366;
RX DOI=10.1002/(sici)1096-9896(199805)185:1<99::aid-path48>3.0.co;2-l;
RA Facchetti F., Blanzuoli L., Vermi W., Notarangelo L.D., Giliani S.,
RA Fiorini M., Fasth A., Stewart D.M., Nelson D.L.;
RT "Defective actin polymerization in EBV-transformed B-cell lines from
RT patients with the Wiskott-Aldrich syndrome.";
RL J. Pathol. 185:99-107(1998).
RN [37]
RP VARIANT WAS LYS-133.
RX PubMed=9445409; DOI=10.1056/nejm199801293380504;
RA Parolini O., Ressmann G., Haas O.A., Pawlowsky J., Gadner H., Knapp W.,
RA Holter W.;
RT "X-linked Wiskott-Aldrich syndrome in a girl.";
RL N. Engl. J. Med. 338:291-295(1998).
RN [38]
RP VARIANT THC1 MET-45.
RX PubMed=11167787; DOI=10.1046/j.1365-2141.2001.02465.x;
RA Ho L.L., Ayling J., Prosser I., Kronenberg H., Iland H., Joshua D.;
RT "Missense C168T in the Wiskott-Aldrich Syndrome protein gene is a common
RT mutation in X-linked thrombocytopenia.";
RL Br. J. Haematol. 112:76-80(2001).
RN [39]
RP VARIANT XLN PRO-270, AND CHARACTERIZATION OF VARIANT XLN PRO-270.
RX PubMed=11242115; DOI=10.1038/85886;
RA Devriendt K., Kim A.S., Mathijs G., Frints S.G.M., Schwartz M.,
RA Van Den Oord J.J., Verhoef G.E.G., Boogaerts M.A., Fryns J.-P., You D.,
RA Rosen M.K., Vandenberghe P.;
RT "Constitutively activating mutation in WASP causes X-linked severe
RT congenital neutropenia.";
RL Nat. Genet. 27:313-317(2001).
RN [40]
RP VARIANTS WAS ARG-73; CYS-86 AND LYS-133, AND VARIANTS THC1 MET-75 AND
RP CYS-83.
RX PubMed=10447259;
RX DOI=10.1002/(sici)1098-1004(1999)14:1<54::aid-humu7>3.0.co;2-e;
RA Lemahieu V., Gastier J.M., Francke U.;
RT "Novel mutations in the Wiskott-Aldrich syndrome protein gene and their
RT effects on transcriptional, translational, and clinical phenotypes.";
RL Hum. Mutat. 14:54-66(1999).
RN [41]
RP VARIANTS THC1 ARG-58 AND ASN-481.
RX PubMed=11877312; DOI=10.1182/blood.v99.6.2268;
RA Notarangelo L.D., Mazza C., Giliani S., D'Aria C., Gandellini F.,
RA Ravelli C., Locatelli M.G., Nelson D.L., Ochs H.D., Notarangelo L.D.;
RT "Missense mutations of the WASP gene cause intermittent X-linked
RT thrombocytopenia.";
RL Blood 99:2268-2269(2002).
RN [42]
RP VARIANTS WAS HIS-52 AND TRP-70.
RX PubMed=11793485; DOI=10.1002/humu.9013;
RA El-Hakeh J., Rosenzweig S., Oleastro M., Basack N., Berozdnik L.,
RA Molina F., Rivas E.M., Zelazko M., Danielian S.;
RT "Wiskott-Aldrich syndrome in Argentina: 17 unique, including nine novel,
RT mutations.";
RL Hum. Mutat. 19:186-187(2002).
RN [43]
RP VARIANT THR-56.
RX PubMed=24115682; DOI=10.1002/pbc.24787;
RA Wada T., Itoh M., Maeba H., Toma T., Niida Y., Saikawa Y., Yachie A.;
RT "Intermittent X-linked thrombocytopenia with a novel WAS gene mutation.";
RL Pediatr. Blood Cancer 61:746-748(2014).
RN [44]
RP VARIANT LYS-131.
RX PubMed=26566883; DOI=10.1136/jmedgenet-2015-103179;
RA Rafiullah R., Aslamkhan M., Paramasivam N., Thiel C., Mustafa G.,
RA Wiemann S., Schlesner M., Wade R.C., Rappold G.A., Berkel S.;
RT "Homozygous missense mutation in the LMAN2L gene segregates with
RT intellectual disability in a large consanguineous Pakistani family.";
RL J. Med. Genet. 53:138-144(2016).
CC -!- FUNCTION: Effector protein for Rho-type GTPases that regulates actin
CC filament reorganization via its interaction with the Arp2/3 complex
CC (PubMed:12235133, PubMed:12769847, PubMed:16275905). Important for
CC efficient actin polymerization (PubMed:8625410, PubMed:12235133,
CC PubMed:16275905). Possible regulator of lymphocyte and platelet
CC function (PubMed:9405671). Mediates actin filament reorganization and
CC the formation of actin pedestals upon infection by pathogenic bacteria
CC (PubMed:18650809). In addition to its role in the cytoplasmic
CC cytoskeleton, also promotes actin polymerization in the nucleus,
CC thereby regulating gene transcription and repair of damaged DNA
CC (PubMed:20574068). Promotes homologous recombination (HR) repair in
CC response to DNA damage by promoting nuclear actin polymerization,
CC leading to drive motility of double-strand breaks (DSBs)
CC (PubMed:29925947). {ECO:0000269|PubMed:12235133,
CC ECO:0000269|PubMed:12769847, ECO:0000269|PubMed:16275905,
CC ECO:0000269|PubMed:18650809, ECO:0000269|PubMed:20574068,
CC ECO:0000269|PubMed:29925947, ECO:0000269|PubMed:8625410,
CC ECO:0000269|PubMed:9405671}.
CC -!- SUBUNIT: Binds the Arp2/3 complex (PubMed:12769847). Interacts with
CC CDC42, RAC, NCK, HCK, FYN, SRC kinase FGR, BTK, ABL1, PSTPIP1, WIP, and
CC to the p85 subunit of PLC-gamma (PubMed:8643625, PubMed:9405671,
CC PubMed:12235133, PubMed:10360578, PubMed:15235593). Interacts (via C-
CC terminus) with ALDOA (PubMed:17329259). Interacts with NCK1 (via SH3
CC domains) (By similarity). Interacts with FCHSD2 (By similarity).
CC {ECO:0000250|UniProtKB:P70315, ECO:0000269|PubMed:10360578,
CC ECO:0000269|PubMed:12235133, ECO:0000269|PubMed:12769847,
CC ECO:0000269|PubMed:15235593, ECO:0000269|PubMed:17329259,
CC ECO:0000269|PubMed:8643625, ECO:0000269|PubMed:9405671}.
CC -!- SUBUNIT: (Microbial infection) Interacts with E.coli effector protein
CC EspF(U). {ECO:0000269|PubMed:18650809}.
CC -!- INTERACTION:
CC P42768; Q9P2A4: ABI3; NbExp=4; IntAct=EBI-346375, EBI-742038;
CC P42768; Q92624: APPBP2; NbExp=3; IntAct=EBI-346375, EBI-743771;
CC P42768; Q06187: BTK; NbExp=4; IntAct=EBI-346375, EBI-624835;
CC P42768; P60953: CDC42; NbExp=12; IntAct=EBI-346375, EBI-81752;
CC P42768; Q14247: CTTN; NbExp=3; IntAct=EBI-346375, EBI-351886;
CC P42768; P08631: HCK; NbExp=9; IntAct=EBI-346375, EBI-346340;
CC P42768; O43639: NCK2; NbExp=3; IntAct=EBI-346375, EBI-713635;
CC P42768; Q8WV41: SNX33; NbExp=3; IntAct=EBI-346375, EBI-2481535;
CC P42768; Q9Y5X1: SNX9; NbExp=2; IntAct=EBI-346375, EBI-77848;
CC P42768; O94875: SORBS2; NbExp=3; IntAct=EBI-346375, EBI-311323;
CC P42768; P11387: TOP1; NbExp=3; IntAct=EBI-346375, EBI-876302;
CC P42768; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-346375, EBI-7353612;
CC P42768; P42768: WAS; NbExp=4; IntAct=EBI-346375, EBI-346375;
CC P42768; O43516: WIPF1; NbExp=25; IntAct=EBI-346375, EBI-346356;
CC P42768; O43516-4: WIPF1; NbExp=3; IntAct=EBI-346375, EBI-12052927;
CC P42768; P0DJ88: espF(U); Xeno; NbExp=3; IntAct=EBI-346375, EBI-10039462;
CC P42768; P08103: Hck; Xeno; NbExp=3; IntAct=EBI-346375, EBI-6248894;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:8625410}. Nucleus {ECO:0000269|PubMed:20574068,
CC ECO:0000269|PubMed:29925947}.
CC -!- TISSUE SPECIFICITY: Expressed predominantly in the thymus. Also found,
CC to a much lesser extent, in the spleen. {ECO:0000269|PubMed:8069912}.
CC -!- DOMAIN: The WH1 (Wasp homology 1) domain may bind a Pro-rich ligand.
CC -!- DOMAIN: The CRIB (Cdc42/Rac-interactive-binding) region binds to the C-
CC terminal WH2 domain in the autoinhibited state of the protein. Binding
CC of Rho-type GTPases to the CRIB induces a conformation change and leads
CC to activation.
CC -!- PTM: Phosphorylated at Tyr-291 by FYN and HCK, inducing WAS effector
CC activity after TCR engagement. Phosphorylation at Tyr-291 enhances WAS
CC activity in promoting actin polymerization and filopodia formation.
CC {ECO:0000269|PubMed:12235133, ECO:0000269|PubMed:12769847,
CC ECO:0000269|PubMed:14707117}.
CC -!- DISEASE: Wiskott-Aldrich syndrome (WAS) [MIM:301000]: An X-linked
CC recessive immunodeficiency characterized by eczema, thrombocytopenia,
CC recurrent infections, and bloody diarrhea. Death usually occurs before
CC age 10. {ECO:0000269|PubMed:10447259, ECO:0000269|PubMed:11793485,
CC ECO:0000269|PubMed:20574068, ECO:0000269|PubMed:7753869,
CC ECO:0000269|PubMed:8528198, ECO:0000269|PubMed:8528199,
CC ECO:0000269|PubMed:8682510, ECO:0000269|PubMed:9098856,
CC ECO:0000269|PubMed:9126958, ECO:0000269|PubMed:9445409,
CC ECO:0000269|PubMed:9683546, ECO:0000269|PubMed:9713366}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Thrombocytopenia 1 (THC1) [MIM:313900]: A form of
CC thrombocytopenia, a hematologic disorder defined by a decrease in the
CC number of platelets in circulating blood, resulting in the potential
CC for increased bleeding and decreased ability for clotting.
CC {ECO:0000269|PubMed:10447259, ECO:0000269|PubMed:11167787,
CC ECO:0000269|PubMed:11877312, ECO:0000269|PubMed:7795648,
CC ECO:0000269|PubMed:8528199}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neutropenia, severe congenital, X-linked (XLN) [MIM:300299]: A
CC disorder of hematopoiesis characterized by maturation arrest of
CC granulopoiesis at the level of promyelocytes with peripheral blood
CC absolute neutrophil counts below 0.5 x 10(9)/l and early onset of
CC severe bacterial infections. {ECO:0000269|PubMed:11242115}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH02961.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH02961.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=WASbase; Note=WAS mutation db;
CC URL="http://structure.bmc.lu.se/idbase/WASbase/";
CC -!- WEB RESOURCE: Name=WASPbase; Note=WAS mutation db;
CC URL="http://pidj.rcai.riken.jp/waspbase/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Wiskott-Aldrich syndrome protein
CC entry;
CC URL="https://en.wikipedia.org/wiki/Wiskott-Aldrich_syndrome_protein";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/42801/WAS";
CC ---------------------------------------------------------------------------
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DR EMBL; U12707; AAA62663.1; -; mRNA.
DR EMBL; U18935; AAA60381.1; -; Genomic_DNA.
DR EMBL; U19927; AAC50140.1; -; mRNA.
DR EMBL; AF115549; AAD26691.1; -; Genomic_DNA.
DR EMBL; AF196970; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002961; AAH02961.1; ALT_INIT; mRNA.
DR EMBL; BC012738; AAH12738.1; -; mRNA.
DR CCDS; CCDS14303.1; -.
DR PIR; A54747; A55197.
DR RefSeq; NP_000368.1; NM_000377.2.
DR PDB; 1CEE; NMR; -; B=230-288.
DR PDB; 1EJ5; NMR; -; A=242-310, A=461-492.
DR PDB; 1T84; NMR; -; A=242-310, A=461-492.
DR PDB; 2A3Z; X-ray; 2.08 A; C=430-458.
DR PDB; 2K42; NMR; -; A=242-310.
DR PDB; 2OT0; X-ray; 2.05 A; E/F/G/H=488-502.
DR PDBsum; 1CEE; -.
DR PDBsum; 1EJ5; -.
DR PDBsum; 1T84; -.
DR PDBsum; 2A3Z; -.
DR PDBsum; 2K42; -.
DR PDBsum; 2OT0; -.
DR AlphaFoldDB; P42768; -.
DR BMRB; P42768; -.
DR SMR; P42768; -.
DR BioGRID; 113293; 82.
DR CORUM; P42768; -.
DR DIP; DIP-431N; -.
DR ELM; P42768; -.
DR IntAct; P42768; 52.
DR MINT; P42768; -.
DR STRING; 9606.ENSP00000365891; -.
DR DrugBank; DB01731; (S)-wiskostatin.
DR iPTMnet; P42768; -.
DR PhosphoSitePlus; P42768; -.
DR BioMuta; WAS; -.
DR EPD; P42768; -.
DR jPOST; P42768; -.
DR MassIVE; P42768; -.
DR MaxQB; P42768; -.
DR PaxDb; 9606-ENSP00000365891; -.
DR PeptideAtlas; P42768; -.
DR ProteomicsDB; 55550; -.
DR Antibodypedia; 701; 565 antibodies from 43 providers.
DR DNASU; 7454; -.
DR Ensembl; ENST00000376701.5; ENSP00000365891.4; ENSG00000015285.12.
DR Ensembl; ENST00000698625.1; ENSP00000513844.1; ENSG00000015285.12.
DR GeneID; 7454; -.
DR KEGG; hsa:7454; -.
DR MANE-Select; ENST00000376701.5; ENSP00000365891.4; NM_000377.3; NP_000368.1.
DR UCSC; uc004dkm.5; human.
DR AGR; HGNC:12731; -.
DR CTD; 7454; -.
DR DisGeNET; 7454; -.
DR GeneCards; WAS; -.
DR GeneReviews; WAS; -.
DR HGNC; HGNC:12731; WAS.
DR HPA; ENSG00000015285; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; WAS; -.
DR MIM; 300299; phenotype.
DR MIM; 300392; gene.
DR MIM; 301000; phenotype.
DR MIM; 313900; phenotype.
DR neXtProt; NX_P42768; -.
DR OpenTargets; ENSG00000015285; -.
DR Orphanet; 906; Wiskott-Aldrich syndrome.
DR Orphanet; 86788; X-linked severe congenital neutropenia.
DR Orphanet; 852; X-linked thrombocytopenia with normal platelets.
DR PharmGKB; PA37342; -.
DR VEuPathDB; HostDB:ENSG00000015285; -.
DR eggNOG; KOG3671; Eukaryota.
DR GeneTree; ENSGT00730000110895; -.
DR HOGENOM; CLU_015385_3_2_1; -.
DR InParanoid; P42768; -.
DR OMA; WIKMVDI; -.
DR OrthoDB; 3837860at2759; -.
DR PhylomeDB; P42768; -.
DR TreeFam; TF316736; -.
DR PathwayCommons; P42768; -.
DR Reactome; R-HSA-202433; Generation of second messenger molecules.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR SignaLink; P42768; -.
DR SIGNOR; P42768; -.
DR BioGRID-ORCS; 7454; 18 hits in 775 CRISPR screens.
DR ChiTaRS; WAS; human.
DR EvolutionaryTrace; P42768; -.
DR GeneWiki; Wiskott%E2%80%93Aldrich_syndrome_protein; -.
DR GenomeRNAi; 7454; -.
DR Pharos; P42768; Tbio.
DR PRO; PR:P42768; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P42768; Protein.
DR Bgee; ENSG00000015285; Expressed in granulocyte and 179 other cell types or tissues.
DR ExpressionAtlas; P42768; baseline and differential.
DR Genevisible; P42768; HS.
DR GO; GO:0015629; C:actin cytoskeleton; TAS:ProtInc.
DR GO; GO:0005884; C:actin filament; IDA:CAFA.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:CAFA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0012506; C:vesicle membrane; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; IEA:InterPro.
DR GO; GO:0030695; F:GTPase regulator activity; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0043274; F:phospholipase binding; IPI:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0017124; F:SH3 domain binding; IPI:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:CAFA.
DR GO; GO:0030041; P:actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0030048; P:actin filament-based movement; IEA:Ensembl.
DR GO; GO:0008154; P:actin polymerization or depolymerization; TAS:ProtInc.
DR GO; GO:0007596; P:blood coagulation; TAS:ProtInc.
DR GO; GO:0032488; P:Cdc42 protein signal transduction; IMP:CAFA.
DR GO; GO:0071346; P:cellular response to type II interferon; IEA:Ensembl.
DR GO; GO:0006952; P:defense response; TAS:ProtInc.
DR GO; GO:0016197; P:endosomal transport; IEA:Ensembl.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; IMP:HGNC-UCL.
DR GO; GO:2000146; P:negative regulation of cell motility; IMP:CACAO.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IMP:CAFA.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:0008064; P:regulation of actin polymerization or depolymerization; IMP:CAFA.
DR GO; GO:0010591; P:regulation of lamellipodium assembly; IGI:CAFA.
DR GO; GO:0051492; P:regulation of stress fiber assembly; IGI:CAFA.
DR GO; GO:0002625; P:regulation of T cell antigen processing and presentation; IMP:CACAO.
DR GO; GO:0042110; P:T cell activation; IEA:Ensembl.
DR CDD; cd00132; CRIB; 1.
DR CDD; cd01205; EVH1_WASP-like; 1.
DR DisProt; DP01171; -.
DR Gene3D; 3.90.810.10; CRIB domain; 2.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR IDEAL; IID00269; -.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR036936; CRIB_dom_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR011026; WAS_C.
DR InterPro; IPR033927; WASPfam_EVH1.
DR InterPro; IPR000697; WH1/EVH1_dom.
DR InterPro; IPR003124; WH2_dom.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00568; WH1; 1.
DR Pfam; PF02205; WH2; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00461; WH1; 1.
DR SMART; SM00246; WH2; 1.
DR SUPFAM; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF47912; Wiscott-Aldrich syndrome protein, WASP, C-terminal domain; 2.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS50229; WH1; 1.
DR PROSITE; PS51082; WH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Disease variant; Nucleus; Phosphoprotein; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801"
FT CHAIN 2..502
FT /note="Actin nucleation-promoting factor WAS"
FT /id="PRO_0000188990"
FT DOMAIN 39..148
FT /note="WH1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00410"
FT DOMAIN 238..251
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT REPEAT 337..346
FT /note="GRSGPLPPXP motif 1"
FT REPEAT 376..385
FT /note="GRSGPLPPXP motif 2"
FT DOMAIN 430..447
FT /note="WH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00406"
FT REGION 146..240
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..502
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..325
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 344..421
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 440..461
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 488..502
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 291
FT /note="Phosphotyrosine; by FYN and HCK"
FT /evidence="ECO:0000269|PubMed:12235133,
FT ECO:0000269|PubMed:14707117, ECO:0007744|PubMed:15592455,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:19690332"
FT MOD_RES 483
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:12769847,
FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:19690332"
FT MOD_RES 484
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:12769847,
FT ECO:0007744|PubMed:18088087"
FT VARIANT 27
FT /note="L -> F (in THC1)"
FT /evidence="ECO:0000269|PubMed:8528199"
FT /id="VAR_005823"
FT VARIANT 30
FT /note="Missing (in THC1)"
FT /evidence="ECO:0000269|PubMed:8528198"
FT /id="VAR_005824"
FT VARIANT 31
FT /note="E -> K (in WAS; dbSNP:rs1557006239)"
FT /evidence="ECO:0000269|PubMed:8528198,
FT ECO:0000269|PubMed:9098856"
FT /id="VAR_005825"
FT VARIANT 43
FT /note="C -> W (in WAS; moderate form)"
FT /evidence="ECO:0000269|PubMed:7753869,
FT ECO:0000269|PubMed:9126958"
FT /id="VAR_008105"
FT VARIANT 45
FT /note="T -> M (in WAS and THC1; dbSNP:rs132630273)"
FT /evidence="ECO:0000269|PubMed:11167787,
FT ECO:0000269|PubMed:7753869, ECO:0000269|PubMed:9098856,
FT ECO:0000269|PubMed:9126958"
FT /id="VAR_008106"
FT VARIANT 48
FT /note="T -> I (in THC1)"
FT /evidence="ECO:0000269|PubMed:8528199"
FT /id="VAR_005826"
FT VARIANT 52
FT /note="Q -> H (in WAS)"
FT /evidence="ECO:0000269|PubMed:11793485"
FT /id="VAR_012710"
FT VARIANT 56
FT /note="A -> T (found in a patient with THC1; uncertain
FT significance)"
FT /evidence="ECO:0000269|PubMed:24115682"
FT /id="VAR_074020"
FT VARIANT 56
FT /note="A -> V (in THC1; dbSNP:rs132630269)"
FT /evidence="ECO:0000269|PubMed:7795648,
FT ECO:0000269|PubMed:9713366"
FT /id="VAR_005827"
FT VARIANT 58
FT /note="P -> L (in WAS)"
FT /evidence="ECO:0000269|PubMed:7753869"
FT /id="VAR_022806"
FT VARIANT 58
FT /note="P -> R (in THC1; dbSNP:rs132630275)"
FT /evidence="ECO:0000269|PubMed:11877312"
FT /id="VAR_033255"
FT VARIANT 70
FT /note="G -> W (in WAS)"
FT /evidence="ECO:0000269|PubMed:11793485"
FT /id="VAR_012711"
FT VARIANT 73
FT /note="C -> R (in WAS; severe form)"
FT /evidence="ECO:0000269|PubMed:10447259"
FT /id="VAR_008107"
FT VARIANT 75
FT /note="V -> M (in THC1; dbSNP:rs782290433)"
FT /evidence="ECO:0000269|PubMed:10447259,
FT ECO:0000269|PubMed:8528198, ECO:0000269|PubMed:8528199,
FT ECO:0000269|PubMed:9126958, ECO:0000269|PubMed:9683546"
FT /id="VAR_005828"
FT VARIANT 82
FT /note="S -> P (in WAS; attenuated form; dbSNP:rs132630272)"
FT /evidence="ECO:0000269|PubMed:8528198"
FT /id="VAR_005829"
FT VARIANT 83
FT /note="Y -> C (in THC1)"
FT /evidence="ECO:0000269|PubMed:10447259"
FT /id="VAR_008108"
FT VARIANT 84
FT /note="F -> L (in WAS; severe form)"
FT /evidence="ECO:0000269|PubMed:9683546"
FT /id="VAR_008109"
FT VARIANT 86
FT /note="R -> C (in WAS)"
FT /evidence="ECO:0000269|PubMed:10447259,
FT ECO:0000269|PubMed:8528198, ECO:0000269|PubMed:9126958"
FT /id="VAR_005832"
FT VARIANT 86
FT /note="R -> H (in WAS; dbSNP:rs132630268)"
FT /evidence="ECO:0000269|PubMed:8528198,
FT ECO:0000269|PubMed:8528199, ECO:0000269|PubMed:8682510"
FT /id="VAR_005830"
FT VARIANT 86
FT /note="R -> L (in WAS; dbSNP:rs132630268)"
FT /evidence="ECO:0000269|PubMed:8528199"
FT /id="VAR_005831"
FT VARIANT 89
FT /note="G -> D (in WAS; mild form; dbSNP:rs139857045)"
FT /evidence="ECO:0000269|PubMed:9683546"
FT /id="VAR_008110"
FT VARIANT 97
FT /note="W -> C (in WAS; attenuated form)"
FT /evidence="ECO:0000269|PubMed:8528198"
FT /id="VAR_005833"
FT VARIANT 131
FT /note="E -> K (in WAS; found in a patient with MRT52;
FT dbSNP:rs146220228)"
FT /evidence="ECO:0000269|PubMed:26566883,
FT ECO:0000269|PubMed:8528199"
FT /id="VAR_005834"
FT VARIANT 133
FT /note="E -> K (in WAS; severe form)"
FT /evidence="ECO:0000269|PubMed:10447259,
FT ECO:0000269|PubMed:7753869, ECO:0000269|PubMed:8528198,
FT ECO:0000269|PubMed:9445409, ECO:0000269|PubMed:9683546"
FT /id="VAR_005835"
FT VARIANT 134
FT /note="A -> T (in WAS)"
FT /evidence="ECO:0000269|PubMed:7753869"
FT /id="VAR_022807"
FT VARIANT 187
FT /note="G -> C (in WAS)"
FT /evidence="ECO:0000269|PubMed:8528199"
FT /id="VAR_005836"
FT VARIANT 236
FT /note="A -> E (in THC1)"
FT /evidence="ECO:0000269|PubMed:7795648"
FT /id="VAR_005837"
FT VARIANT 270
FT /note="L -> P (in XLN; a constitutively activating
FT mutation; dbSNP:rs132630274)"
FT /evidence="ECO:0000269|PubMed:11242115"
FT /id="VAR_033256"
FT VARIANT 476
FT /note="K -> E (in WAS)"
FT /evidence="ECO:0000269|PubMed:8528198"
FT /id="VAR_005838"
FT VARIANT 477
FT /note="R -> K (in THC1)"
FT /evidence="ECO:0000269|PubMed:8528199"
FT /id="VAR_005839"
FT VARIANT 481
FT /note="I -> N (in THC1; dbSNP:rs132630276)"
FT /evidence="ECO:0000269|PubMed:11877312"
FT /id="VAR_033257"
FT CONFLICT 332
FT /note="V -> A (in Ref. 4; AAD26691)"
FT /evidence="ECO:0000305"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:1CEE"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:1CEE"
FT TURN 254..256
FT /evidence="ECO:0007829|PDB:1CEE"
FT TURN 260..262
FT /evidence="ECO:0007829|PDB:1EJ5"
FT HELIX 265..271
FT /evidence="ECO:0007829|PDB:1CEE"
FT TURN 272..275
FT /evidence="ECO:0007829|PDB:1CEE"
FT HELIX 278..281
FT /evidence="ECO:0007829|PDB:1EJ5"
FT HELIX 284..296
FT /evidence="ECO:0007829|PDB:1EJ5"
FT HELIX 299..309
FT /evidence="ECO:0007829|PDB:1EJ5"
FT HELIX 432..440
FT /evidence="ECO:0007829|PDB:2A3Z"
SQ SEQUENCE 502 AA; 52913 MW; 7228428672B7CB78 CRC64;
MSGGPMGGRP GGRGAPAVQQ NIPSTLLQDH ENQRLFEMLG RKCLTLATAV VQLYLALPPG
AEHWTKEHCG AVCFVKDNPQ KSYFIRLYGL QAGRLLWEQE LYSQLVYSTP TPFFHTFAGD
DCQAGLNFAD EDEAQAFRAL VQEKIQKRNQ RQSGDRRQLP PPPTPANEER RGGLPPLPLH
PGGDQGGPPV GPLSLGLATV DIQNPDITSS RYRGLPAPGP SPADKKRSGK KKISKADIGA
PSGFKHVSHV GWDPQNGFDV NNLDPDLRSL FSRAGISEAQ LTDAETSKLI YDFIEDQGGL
EAVRQEMRRQ EPLPPPPPPS RGGNQLPRPP IVGGNKGRSG PLPPVPLGIA PPPPTPRGPP
PPGRGGPPPP PPPATGRSGP LPPPPPGAGG PPMPPPPPPP PPPPSSGNGP APPPLPPALV
PAGGLAPGGG RGALLDQIRQ GIQLNKTPGA PESSALQPPP QSSEGLVGAL MHVMQKRSRA
IHSSDEGEDQ AGDEDEDDEW DD
//
