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Protein

Wiskott-Aldrich syndrome protein

Gene

WAS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

  • actin binding Source: InterPro
  • GTPase regulator activity Source: ProtInc
  • identical protein binding Source: IntAct
  • phospholipase binding Source: BHF-UCL
  • protein kinase binding Source: BHF-UCL
  • Rac GTPase binding Source: CAFA
  • SH3 domain binding Source: UniProtKB
  • small GTPase binding Source: CAFA

GO - Biological processi

  • actin filament-based movement Source: Ensembl
  • actin filament polymerization Source: Ensembl
  • actin polymerization or depolymerization Source: ProtInc
  • blood coagulation Source: ProtInc
  • Cdc42 protein signal transduction Source: CAFA
  • cellular response to interferon-gamma Source: Ensembl
  • defense response Source: ProtInc
  • endosomal transport Source: Ensembl
  • epidermis development Source: ProtInc
  • Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
  • immune response Source: HGNC
  • negative regulation of cell motility Source: CACAO
  • negative regulation of stress fiber assembly Source: CAFA
  • positive regulation of Arp2/3 complex-mediated actin nucleation Source: InterPro
  • protein-containing complex assembly Source: ProtInc
  • regulation of actin polymerization or depolymerization Source: CAFA
  • regulation of lamellipodium assembly Source: CAFA
  • regulation of stress fiber assembly Source: CAFA
  • regulation of T cell antigen processing and presentation Source: CACAO
  • T cell activation Source: Ensembl
  • T cell receptor signaling pathway Source: Reactome

Enzyme and pathway databases

ReactomeiR-HSA-202433 Generation of second messenger molecules
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-5663213 RHO GTPases Activate WASPs and WAVEs
SIGNORiP42768

Names & Taxonomyi

Protein namesi
Recommended name:
Wiskott-Aldrich syndrome protein
Short name:
WASp
Gene namesi
Name:WAS
Synonyms:IMD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000015285.10
HGNCiHGNC:12731 WAS
MIMi300392 gene
neXtProtiNX_P42768

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

Pathology & Biotechi

Involvement in diseasei

Wiskott-Aldrich syndrome (WAS)11 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn X-linked recessive immunodeficiency characterized by eczema, thrombocytopenia, recurrent infections, and bloody diarrhea. Death usually occurs before age 10.
See also OMIM:301000
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00582531E → K in WAS. 2 Publications1
Natural variantiVAR_00810543C → W in WAS; moderate form. 2 Publications1
Natural variantiVAR_01271052Q → H in WAS. 1 Publication1
Natural variantiVAR_02280658P → L in WAS. 1 Publication1
Natural variantiVAR_01271170G → W in WAS. 1 Publication1
Natural variantiVAR_00810773C → R in WAS; severe form. 1 Publication1
Natural variantiVAR_00582982S → P in WAS; attenuated form. 1 PublicationCorresponds to variant dbSNP:rs132630272EnsemblClinVar.1
Natural variantiVAR_00810984F → L in WAS; severe form. 1 Publication1
Natural variantiVAR_00583286R → C in WAS. 3 Publications1
Natural variantiVAR_00583086R → H in WAS. 3 PublicationsCorresponds to variant dbSNP:rs132630268EnsemblClinVar.1
Natural variantiVAR_00583186R → L in WAS. 1 PublicationCorresponds to variant dbSNP:rs132630268EnsemblClinVar.1
Natural variantiVAR_00811089G → D in WAS; mild form. 1 PublicationCorresponds to variant dbSNP:rs139857045Ensembl.1
Natural variantiVAR_00583397W → C in WAS; attenuated form. 1 Publication1
Natural variantiVAR_005834131E → K in WAS; found in a patient with MRT52. 2 PublicationsCorresponds to variant dbSNP:rs146220228EnsemblClinVar.1
Natural variantiVAR_005835133E → K in WAS; severe form. 5 Publications1
Natural variantiVAR_022807134A → T in WAS. 1 Publication1
Natural variantiVAR_005836187G → C in WAS. 1 Publication1
Natural variantiVAR_005838476K → E in WAS. 1 Publication1
Thrombocytopenia 1 (THC1)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionThrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting.
See also OMIM:313900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00582327L → F in THC1. 1 Publication1
Natural variantiVAR_00582430Missing in THC1. 1 Publication1
Natural variantiVAR_00582648T → I in THC1. 1 Publication1
Natural variantiVAR_00582756A → V in THC1. 2 PublicationsCorresponds to variant dbSNP:rs132630269EnsemblClinVar.1
Natural variantiVAR_03325558P → R in THC1. 1 PublicationCorresponds to variant dbSNP:rs132630275EnsemblClinVar.1
Natural variantiVAR_00582875V → M in THC1. 5 PublicationsCorresponds to variant dbSNP:rs782290433EnsemblClinVar.1
Natural variantiVAR_00810883Y → C in THC1. 1 Publication1
Natural variantiVAR_005837236A → E in THC1. 1 Publication1
Natural variantiVAR_005839477R → K in THC1. 1 Publication1
Natural variantiVAR_033257481I → N in THC1. 1 PublicationCorresponds to variant dbSNP:rs132630276EnsemblClinVar.1
Neutropenia, severe congenital, X-linked (XLN)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
See also OMIM:300299
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033256270L → P in XLN; a constitutively activating mutation. 1 PublicationCorresponds to variant dbSNP:rs132630274EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7454
GeneReviewsiWAS
MalaCardsiWAS
MIMi300299 phenotype
301000 phenotype
313900 phenotype
OpenTargetsiENSG00000015285
Orphaneti906 Wiskott-Aldrich syndrome
86788 X-linked severe congenital neutropenia
852 X-linked thrombocytopenia with normal platelets
PharmGKBiPA37342

Chemistry databases

DrugBankiDB01731 (S)-Wiskostatin

Polymorphism and mutation databases

BioMutaiWAS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00001889902 – 502Wiskott-Aldrich syndrome proteinAdd BLAST501

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei221PhosphoserineCombined sources1
Modified residuei291Phosphotyrosine; by FYN and HCKCombined sources2 Publications1
Modified residuei483Phosphoserine; by CK2Combined sources1 Publication1
Modified residuei484Phosphoserine; by CK2Combined sources1 Publication1

Post-translational modificationi

Phosphorylated at Tyr-291 by FYN and HCK, inducing WAS effector activity after TCR engagement. Phosphorylation at Tyr-291 enhances WAS activity in promoting actin polymerization and filopodia formation.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP42768
MaxQBiP42768
PaxDbiP42768
PeptideAtlasiP42768
PRIDEiP42768
ProteomicsDBi55550

PTM databases

iPTMnetiP42768
PhosphoSitePlusiP42768

Expressioni

Tissue specificityi

Expressed predominantly in the thymus. Also found, to a much lesser extent, in the spleen.1 Publication

Gene expression databases

BgeeiENSG00000015285
CleanExiHS_WAS
ExpressionAtlasiP42768 baseline and differential
GenevisibleiP42768 HS

Organism-specific databases

HPAiCAB004290
HPA002022

Interactioni

Subunit structurei

Interacts with NCK1 (via SH3 domains) (By similarity). Interacts with CDC42, RAC, NCK, HCK, FYN, SRC kinase FGR, BTK, ABL1, PSTPIP1, WIP, and to the p85 subunit of PLC-gamma. Binds the Arp2/3 complex. Interacts (via C-terminus) with ALDOA. Interacts with E.coli effector protein EspF(U).By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • actin binding Source: InterPro
  • identical protein binding Source: IntAct
  • phospholipase binding Source: BHF-UCL
  • protein kinase binding Source: BHF-UCL
  • Rac GTPase binding Source: CAFA
  • SH3 domain binding Source: UniProtKB
  • small GTPase binding Source: CAFA

Protein-protein interaction databases

BioGridi113293, 63 interactors
CORUMiP42768
DIPiDIP-431N
ELMiP42768
IntActiP42768, 47 interactors
MINTiP42768
STRINGi9606.ENSP00000365891

Structurei

Secondary structure

1502
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni235 – 237Combined sources3
Beta strandi245 – 250Combined sources6
Turni254 – 256Combined sources3
Turni260 – 262Combined sources3
Helixi265 – 271Combined sources7
Turni272 – 275Combined sources4
Helixi278 – 281Combined sources4
Helixi284 – 296Combined sources13
Helixi299 – 309Combined sources11
Helixi432 – 440Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CEENMR-B230-288[»]
1EJ5NMR-A242-310[»]
A461-492[»]
1T84NMR-A242-310[»]
A461-492[»]
2A3ZX-ray2.08C430-458[»]
2K42NMR-A242-310[»]
2OT0X-ray2.05E/F/G/H488-502[»]
ProteinModelPortaliP42768
SMRiP42768
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42768

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini39 – 148WH1PROSITE-ProRule annotationAdd BLAST110
Domaini238 – 251CRIBPROSITE-ProRule annotationAdd BLAST14
Repeati337 – 346GRSGPLPPXP motif 110
Repeati376 – 385GRSGPLPPXP motif 210
Domaini430 – 447WH2PROSITE-ProRule annotationAdd BLAST18

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi160 – 165Poly-Pro6
Compositional biasi312 – 319Poly-Pro8
Compositional biasi351 – 356Poly-Pro6
Compositional biasi359 – 362Poly-Pro4
Compositional biasi367 – 373Poly-Pro7
Compositional biasi380 – 386Poly-Pro7
Compositional biasi391 – 404Poly-ProAdd BLAST14
Compositional biasi485 – 502Asp/Glu-rich (acidic)Add BLAST18

Domaini

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.

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3671 Eukaryota
ENOG4111M1J LUCA
GeneTreeiENSGT00730000110895
HOGENOMiHOG000143378
HOVERGENiHBG000222
InParanoidiP42768
KOiK05747
OMAiEMRRQEP
OrthoDBiEOG091G0VCD
PhylomeDBiP42768
TreeFamiTF316736

Family and domain databases

CDDicd00132 CRIB, 1 hit
cd01205 EVH1_WASP-like, 1 hit
Gene3Di2.30.29.30, 1 hit
3.90.810.10, 2 hits
InterProiView protein in InterPro
IPR000095 CRIB_dom
IPR036936 CRIB_dom_sf
IPR011993 PH-like_dom_sf
IPR027641 WASP
IPR011026 WASP_C
IPR033927 WASPfam_EVH1
IPR000697 WH1/EVH1_dom
IPR003124 WH2_dom
PANTHERiPTHR23202:SF35 PTHR23202:SF35, 1 hit
PfamiView protein in Pfam
PF00786 PBD, 1 hit
PF00568 WH1, 1 hit
PF02205 WH2, 1 hit
SMARTiView protein in SMART
SM00285 PBD, 1 hit
SM00461 WH1, 1 hit
SM00246 WH2, 1 hit
SUPFAMiSSF47912 SSF47912, 2 hits
PROSITEiView protein in PROSITE
PS50108 CRIB, 1 hit
PS50229 WH1, 1 hit
PS51082 WH2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P42768-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGGPMGGRP GGRGAPAVQQ NIPSTLLQDH ENQRLFEMLG RKCLTLATAV
60 70 80 90 100
VQLYLALPPG AEHWTKEHCG AVCFVKDNPQ KSYFIRLYGL QAGRLLWEQE
110 120 130 140 150
LYSQLVYSTP TPFFHTFAGD DCQAGLNFAD EDEAQAFRAL VQEKIQKRNQ
160 170 180 190 200
RQSGDRRQLP PPPTPANEER RGGLPPLPLH PGGDQGGPPV GPLSLGLATV
210 220 230 240 250
DIQNPDITSS RYRGLPAPGP SPADKKRSGK KKISKADIGA PSGFKHVSHV
260 270 280 290 300
GWDPQNGFDV NNLDPDLRSL FSRAGISEAQ LTDAETSKLI YDFIEDQGGL
310 320 330 340 350
EAVRQEMRRQ EPLPPPPPPS RGGNQLPRPP IVGGNKGRSG PLPPVPLGIA
360 370 380 390 400
PPPPTPRGPP PPGRGGPPPP PPPATGRSGP LPPPPPGAGG PPMPPPPPPP
410 420 430 440 450
PPPPSSGNGP APPPLPPALV PAGGLAPGGG RGALLDQIRQ GIQLNKTPGA
460 470 480 490 500
PESSALQPPP QSSEGLVGAL MHVMQKRSRA IHSSDEGEDQ AGDEDEDDEW

DD
Length:502
Mass (Da):52,913
Last modified:January 23, 2007 - v4
Checksum:i7228428672B7CB78
GO

Sequence cautioni

The sequence AAH02961 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH02961 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti332V → A in AAD26691 (PubMed:10066431).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00582327L → F in THC1. 1 Publication1
Natural variantiVAR_00582430Missing in THC1. 1 Publication1
Natural variantiVAR_00582531E → K in WAS. 2 Publications1
Natural variantiVAR_00810543C → W in WAS; moderate form. 2 Publications1
Natural variantiVAR_00810645T → M in WAS and THC1. 4 PublicationsCorresponds to variant dbSNP:rs132630273EnsemblClinVar.1
Natural variantiVAR_00582648T → I in THC1. 1 Publication1
Natural variantiVAR_01271052Q → H in WAS. 1 Publication1
Natural variantiVAR_07402056A → T Found in a patient with THC1; unknown pathological significance. 1 Publication1
Natural variantiVAR_00582756A → V in THC1. 2 PublicationsCorresponds to variant dbSNP:rs132630269EnsemblClinVar.1
Natural variantiVAR_02280658P → L in WAS. 1 Publication1
Natural variantiVAR_03325558P → R in THC1. 1 PublicationCorresponds to variant dbSNP:rs132630275EnsemblClinVar.1
Natural variantiVAR_01271170G → W in WAS. 1 Publication1
Natural variantiVAR_00810773C → R in WAS; severe form. 1 Publication1
Natural variantiVAR_00582875V → M in THC1. 5 PublicationsCorresponds to variant dbSNP:rs782290433EnsemblClinVar.1
Natural variantiVAR_00582982S → P in WAS; attenuated form. 1 PublicationCorresponds to variant dbSNP:rs132630272EnsemblClinVar.1
Natural variantiVAR_00810883Y → C in THC1. 1 Publication1
Natural variantiVAR_00810984F → L in WAS; severe form. 1 Publication1
Natural variantiVAR_00583286R → C in WAS. 3 Publications1
Natural variantiVAR_00583086R → H in WAS. 3 PublicationsCorresponds to variant dbSNP:rs132630268EnsemblClinVar.1
Natural variantiVAR_00583186R → L in WAS. 1 PublicationCorresponds to variant dbSNP:rs132630268EnsemblClinVar.1
Natural variantiVAR_00811089G → D in WAS; mild form. 1 PublicationCorresponds to variant dbSNP:rs139857045Ensembl.1
Natural variantiVAR_00583397W → C in WAS; attenuated form. 1 Publication1
Natural variantiVAR_005834131E → K in WAS; found in a patient with MRT52. 2 PublicationsCorresponds to variant dbSNP:rs146220228EnsemblClinVar.1
Natural variantiVAR_005835133E → K in WAS; severe form. 5 Publications1
Natural variantiVAR_022807134A → T in WAS. 1 Publication1
Natural variantiVAR_005836187G → C in WAS. 1 Publication1
Natural variantiVAR_005837236A → E in THC1. 1 Publication1
Natural variantiVAR_033256270L → P in XLN; a constitutively activating mutation. 1 PublicationCorresponds to variant dbSNP:rs132630274EnsemblClinVar.1
Natural variantiVAR_005838476K → E in WAS. 1 Publication1
Natural variantiVAR_005839477R → K in THC1. 1 Publication1
Natural variantiVAR_033257481I → N in THC1. 1 PublicationCorresponds to variant dbSNP:rs132630276EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U12707 mRNA Translation: AAA62663.1
U18935 Genomic DNA Translation: AAA60381.1
U19927 mRNA Translation: AAC50140.1
AF115549 Genomic DNA Translation: AAD26691.1
AF196970 Genomic DNA No translation available.
BC002961 mRNA Translation: AAH02961.1 Different initiation.
BC012738 mRNA Translation: AAH12738.1
CCDSiCCDS14303.1
PIRiA54747 A55197
RefSeqiNP_000368.1, NM_000377.2
UniGeneiHs.2157

Genome annotation databases

EnsembliENST00000376701; ENSP00000365891; ENSG00000015285
GeneIDi7454
KEGGihsa:7454
UCSCiuc004dkm.5 human

Similar proteinsi

Entry informationi

Entry nameiWASP_HUMAN
AccessioniPrimary (citable) accession number: P42768
Secondary accession number(s): Q9BU11, Q9UNJ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2007
Last modified: June 20, 2018
This is version 215 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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