Skip Header

 
Contribute Send feedback

Reviewed, UniProtKB/Swiss-Prot P42768 (WASP_HUMAN)

Last modified November 25, 2008. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Wiskott-Aldrich syndrome protein
      Short name=WASp
Gene names
Name: WAS
Synonyms: IMD2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length502 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Effector protein for Rho-type GTPases, providing a link with the Arp2/3 complex that regulates the structure and dynamics of the actin cytoskeleton. Important for efficient actin polymerization. Possible regulator of lymphocyte and platelet function.

Subunit structure

Binds to CDC42, RAC, NCK, FYN, SRC kinase FGR, BTK, ABL, PSTPIP1, WIP, and to the p85 subunit of PLC-gamma. Binds the Arp2/3 complex.

Subcellular location

Cytoplasmcytoskeleton.

Tissue specificity

Expressed predominantly in the thymus. Also found, to a much lesser extent, in the spleen.

Domain

The WH1 (Wasp homology 1) domain may bind a Pro-rich ligand.

The CRIB (Cdc42/Rac-interactive-binding) region binds to the C-terminal WH2 domain in the autoinhibited state of the protein. Binding of Rho-type GTPases to the CRIB induces a conformation change and leads to activation.

Involvement in disease

Defects in WAS are the cause of Wiskott-Aldrich syndrome (WAS) [MIM:301000]; also known as eczema-thrombocytopenia-immunodeficiency syndrome. WAS is an X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, recurrent infections, and bloody diarrhea. Death usually occurs before age 10.

Defects in WAS are the cause of isolated X-linked thrombocytopenia (XLT) [MIM:313900]. XLT is clinically mild with small platelets and subclinical leukocyte abnormalities.

Defects in WAS are a cause of X-linked severe congenital neutropenia (XLN) [MIM:300299]. XLN is an X-linked immunodeficiency syndrome characterized by recurrent major bacterial infections, severe congenital neutropenia, and monocytopenia.

Sequence similarities

Contains 1 CRIB domain.

Contains 1 WH1 domain.

Contains 1 WH2 domain.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed
Chain2 – 502501Wiskott-Aldrich syndrome protein
PRO_0000188990

Regions

Domain39 – 148110WH1
Domain238 – 25114CRIB
Repeat337 – 34610GRSGPLPPXP motif 1
Repeat376 – 38510GRSGPLPPXP motif 2
Domain430 – 44718WH2
Compositional bias160 – 1656Poly-Pro
Compositional bias312 – 3198Poly-Pro
Compositional bias351 – 3566Poly-Pro
Compositional bias359 – 3624Poly-Pro
Compositional bias367 – 3737Poly-Pro
Compositional bias380 – 3867Poly-Pro
Compositional bias391 – 40414Poly-Pro
Compositional bias485 – 50218Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue2911Phosphotyrosine
Modified residue4831Phosphoserine; by CK2
Modified residue4841Phosphoserine; by CK2

Natural variations

Natural variant271L → F in XLT.
VAR_005823
Natural variant301Missing in XLT.
VAR_005824
Natural variant311E → K in WAS.
VAR_005825
Natural variant431C → W in WAS; moderate form.
VAR_008105
Natural variant451T → M in WAS and XLT.
VAR_008106
Natural variant481T → I in XLT.
VAR_005826
Natural variant521Q → H in WAS.
VAR_012710
Natural variant561A → V in XLT.
VAR_005827
Natural variant581P → L in WAS.
VAR_022806
Natural variant581P → R in XLT.
VAR_033255
Natural variant701G → W in WAS.
VAR_012711
Natural variant731C → R in WAS; severe form.
VAR_008107
Natural variant751V → M in XLT.
VAR_005828
Natural variant821S → P in WAS; attenuated form.
VAR_005829
Natural variant831Y → C in XLT.
VAR_008108
Natural variant841F → L in WAS; severe form.
VAR_008109
Natural variant861R → C in WAS.
VAR_005832
Natural variant861R → H in WAS.
VAR_005830
Natural variant861R → L in WAS.
VAR_005831
Natural variant891G → D in WAS; mild form.
VAR_008110
Natural variant971W → C in WAS; attenuated form.
VAR_005833
Natural variant1311E → K in WAS.
VAR_005834
Natural variant1331E → K in WAS; severe form.
VAR_005835
Natural variant1341A → T in WAS.
VAR_022807
Natural variant1871G → C in WAS.
VAR_005836
Natural variant2361A → E in XLT.
VAR_005837
Natural variant2701L → P in XLN; a constitutively activating mutation.
VAR_033256
Natural variant4761K → E in WAS.
VAR_005838
Natural variant4771R → K in XLT.
VAR_005839
Natural variant4811I → N in XLT.
VAR_033257

Experimental info

Sequence conflict3321V → A in AAD26691. Ref.4

Secondary structure

.................. 502
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P42768-1 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 7228428672B7CB78

FASTA50252,913
        10         20         30         40         50         60 
MSGGPMGGRP GGRGAPAVQQ NIPSTLLQDH ENQRLFEMLG RKCLTLATAV VQLYLALPPG 

        70         80         90        100        110        120 
AEHWTKEHCG AVCFVKDNPQ KSYFIRLYGL QAGRLLWEQE LYSQLVYSTP TPFFHTFAGD 

       130        140        150        160        170        180 
DCQAGLNFAD EDEAQAFRAL VQEKIQKRNQ RQSGDRRQLP PPPTPANEER RGGLPPLPLH 

       190        200        210        220        230        240 
PGGDQGGPPV GPLSLGLATV DIQNPDITSS RYRGLPAPGP SPADKKRSGK KKISKADIGA 

       250        260        270        280        290        300 
PSGFKHVSHV GWDPQNGFDV NNLDPDLRSL FSRAGISEAQ LTDAETSKLI YDFIEDQGGL 

       310        320        330        340        350        360 
EAVRQEMRRQ EPLPPPPPPS RGGNQLPRPP IVGGNKGRSG PLPPVPLGIA PPPPTPRGPP 

       370        380        390        400        410        420 
PPGRGGPPPP PPPATGRSGP LPPPPPGAGG PPMPPPPPPP PPPPSSGNGP APPPLPPALV 

       430        440        450        460        470        480 
PAGGLAPGGG RGALLDQIRQ GIQLNKTPGA PESSALQPPP QSSEGLVGAL MHVMQKRSRA 

       490        500 
IHSSDEGEDQ AGDEDEDDEW DD 

« Hide

References

« Hide 'large scale' references
[1]"Isolation of a novel gene mutated in Wiskott-Aldrich syndrome."
Derry J.M.J., Ochs H.D., Francke U.
Cell 78:635-644(1994) [PubMed: 8069912] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY.
Tissue: T-cell.
[2]Erratum
Derry J.M.J., Ochs H.D., Francke U.
Cell 79:923-923(1994) [PubMed: 8001129] [Abstract]
[3]"Identification of mutations in the Wiskott-Aldrich syndrome gene and characterization of a polymorphic dinucleotide repeat at DXS6940, adjacent to the disease gene."
Kwan S.-P., Hagemann T.L., Radtke B.E., Blaese R.M., Rosen F.S.
Proc. Natl. Acad. Sci. U.S.A. 92:4706-4710(1995) [PubMed: 7753869] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS WAS TRP-43; MET-45; LEU-58; LYS-133 AND THR-134.
[4]"The identification and characterization of two promoters and the complete genomic sequence for the Wiskott-Aldrich syndrome gene."
Hagemann T.L., Kwan S.-P.
Biochem. Biophys. Res. Commun. 256:104-109(1999) [PubMed: 10066431] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed: 15772651] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res.