Reviewed, UniProtKB/Swiss-Prot P42768 (WASP_HUMAN)

Names and origin

Protein names

Recommended name:
    Wiskott-Aldrich syndrome protein
      Short name=WASp

Gene names

Name:	WAS
Synonyms:	IMD2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	502 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Cytoplasm › cytoskeleton.
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.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton
Disease	Disease mutation
Domain	Repeat
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	blood coagulation Ref.1 Traceable author statement. Source: ProtInc defense response Ref.1 Traceable author statement. Source: ProtInc epidermis development Ref.1 Traceable author statement. Source: ProtInc immune response Ref.1 Inferred from mutant phenotype. Source: HGNC
Cellular component	actin cytoskeleton Traceable author statement. Source: ProtInc cytoplasm Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay. Source: HPA
Molecular function	identical protein binding Ref.11 Inferred from physical interaction. Source: IntAct small GTPase regulator activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-346375,EBI-346375
CDC42	P60953	6	EBI-346375,EBI-81752
Cdc42	P60766	1	EBI-346375,EBI-81763	From a different organism.
HCK	P08631	2	EBI-346375,EBI-346340
WIPF1	O43516	6	EBI-346375,EBI-346356

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 502

501

Wiskott-Aldrich syndrome protein

PRO_0000188990

Regions

Domain

39 – 148

110

WH1

Domain

238 – 251

14

CRIB

Repeat

337 – 346

10

GRSGPLPPXP motif 1

Repeat

376 – 385

10

GRSGPLPPXP motif 2

Domain

430 – 447

18

WH2

Compositional bias

160 – 165

6

Poly-Pro

Compositional bias

312 – 319

8

Poly-Pro

Compositional bias

351 – 356

6

Poly-Pro

Compositional bias

359 – 362

4

Poly-Pro

Compositional bias

367 – 373

7

Poly-Pro

Compositional bias

380 – 386

7

Poly-Pro

Compositional bias

391 – 404

14

Poly-Pro

Compositional bias

485 – 502

18

Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue

291

1

Phosphotyrosine

Modified residue

483

1

Phosphoserine; by CK2

Modified residue

484

1

Phosphoserine; by CK2

Natural variations

Natural variant

27

1

L → F in XLT.

VAR_005823

Natural variant

30

1

Missing in XLT.

VAR_005824

Natural variant

31

1

E → K in WAS.

VAR_005825

Natural variant

43

1

C → W in WAS; moderate form.

VAR_008105

Natural variant

45

1

T → M in WAS and XLT.

VAR_008106

Natural variant

48

1

T → I in XLT.

VAR_005826

Natural variant

52

1

Q → H in WAS.

VAR_012710

Natural variant

56

1

A → V in XLT.

VAR_005827

Natural variant

58

1

P → L in WAS.

VAR_022806

Natural variant

58

1

P → R in XLT.

VAR_033255

Natural variant

70

1

G → W in WAS.

VAR_012711

Natural variant

73

1

C → R in WAS; severe form.

VAR_008107

Natural variant

75

1

V → M in XLT.

VAR_005828

Natural variant

82

1

S → P in WAS; attenuated form.

VAR_005829

Natural variant

83

1

Y → C in XLT.

VAR_008108

Natural variant

84

1

F → L in WAS; severe form.

VAR_008109

Natural variant

86

1

R → C in WAS.

VAR_005832

Natural variant

86

1

R → H in WAS.

VAR_005830

Natural variant

86

1

R → L in WAS.

VAR_005831

Natural variant

89

1

G → D in WAS; mild form.

VAR_008110

Natural variant

97

1

W → C in WAS; attenuated form.

VAR_005833

Natural variant

131

1

E → K in WAS.

VAR_005834

Natural variant

133

1

E → K in WAS; severe form.

VAR_005835

Natural variant

134

1

A → T in WAS.

VAR_022807

Natural variant

187

1

G → C in WAS.

VAR_005836

Natural variant

236

1

A → E in XLT.

VAR_005837

Natural variant

270

1

L → P in XLN; a constitutively activating mutation.

VAR_033256

Natural variant

476

1

K → E in WAS.

VAR_005838

Natural variant

477

1

R → K in XLT.

VAR_005839

Natural variant

481

1

I → N in XLT.

VAR_033257

Experimental info

Sequence conflict

332

1

V → A in AAD26691. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

502

Helix Strand Turn

Details...

Turn

235 – 237

3

Beta strand

245 – 250

6

Turn

254 – 256

3

Helix

265 – 271

7

Turn

272 – 275

4

Helix

289 – 296

8

Helix

300 – 307

8

Beta strand

315 – 317

3

Helix

432 – 440

9

Sequences

	Sequence		Length	Mass (Da)
	P42768-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 7228428672B7CB78	FASTA	502	52,913
	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

References

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[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. , 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.