O00401 (WASL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neural Wiskott-Aldrich syndrome protein
Short name=N-WASP

Gene names

Name:

WASL

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	505 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulates actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex. Binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression. Ref.12
Subunit structure	Binds actin and the Arp2/3 complex. Interacts with CDC42. Binds to SH3 domains of GRB2. Interacts with the C-terminal SH3 domain of DNMBP. Interacts with SNX9. Interacts with the WW domains of PRPF40A/FBP11. Interacts with PTK2/FAK1 By similarity. Interacts with NOSTRIN. Interacts with Shigella flexneri protein IcsA. The interaction with IcsA enhances the affinity of WASL for Arp2/3, thus assembling a tight complex which has maximal activity in actin assembly. Interacts with E.coli effector protein EspF(U). Identified in a complex containing at least WASL, BAIAP2L1 and E.coli EspF(U). Binds to TNK2. Ref.4 Ref.5 Ref.6 Ref.7 Ref.12
Subcellular location	Cytoplasm › cytoskeleton By similarity. Nucleus By similarity. Note: Preferentially localized in the cytoplasm when phosphorylated and in the nucleus when unphosphorylated By similarity.
Post-translational modification	Phosphorylation at Ser-242, Tyr-256, Ser-484 and Ser-485 enhances actin polymerization activity.
Sequence similarities	Contains 1 CRIB domain. Contains 1 WH1 domain. Contains 2 WH2 domains.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Cytoskeleton Nucleus
Domain	Repeat
Ligand	Actin-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	actin polymerization or depolymerization Traceable author statement. Source: ProtInc axon guidance Traceable author statement. Source: Reactome cellular component movement Traceable author statement. Source: ProtInc nitric oxide metabolic process Traceable author statement. Source: Reactome protein complex assembly Traceable author statement. Source: ProtInc regulation of nitric-oxide synthase activity Traceable author statement. Source: Reactome regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	actin cytoskeleton Traceable author statement. Source: ProtInc cytosol Traceable author statement. Source: Reactome endocytic vesicle membrane Traceable author statement. Source: Reactome nucleolus Inferred from direct assay. Source: HPA plasma membrane Traceable author statement. Source: Reactome
Molecular function	actin binding Inferred from electronic annotation. Source: UniProtKB-KW small GTPase regulator activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC42	P60953	3	EBI-957615,EBI-81752
Fnbp1	Q8R511	2	EBI-957615,EBI-1111424	From a different organism.
GRB2	P62993	3	EBI-957615,EBI-401755
SORBS3	O60504-2	2	EBI-957615,EBI-1222956

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 505

505

Neural Wiskott-Aldrich syndrome protein

PRO_0000189000

Regions

Domain

34 – 141

108

WH1

Domain

203 – 216

14

CRIB

Domain

405 – 422

18

WH2 1

Domain

433 – 450

18

WH2 2

Compositional bias

277 – 392

116

Pro-rich

Compositional bias

485 – 505

21

Asp-rich

Amino acid modifications

Modified residue

242

1

Phosphoserine; by TNK2 Ref.6

Modified residue

256

1

Phosphotyrosine; by FAK1 and TNK2 Ref.6 Ref.8 Ref.9 Ref.11

Modified residue

484

1

Phosphoserine Ref.10

Modified residue

485

1

Phosphoserine Ref.10

Experimental info

Sequence conflict

76

1

Y → H in BAA20128. Ref.1

Sequence conflict

201

1

A → G in BAA20128. Ref.1

Sequence conflict

223

1

F → S in BAA20128. Ref.1

Sequence conflict

242

1

S → L in BAA20128. Ref.1

Sequence conflict

248

1

D → E in BAA20128. Ref.1

Sequence conflict

252

1

S → L in BAA20128. Ref.1

Sequence conflict

296

1

N → S in BAA20128. Ref.1

Sequence conflict

333

1

A → E in BAA20128. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

505

Helix Strand Turn

Details...

Helix

9 – 11

3

Beta strand

21 – 23

3

Beta strand

38 – 52

15

Turn

53 – 55

3

Beta strand

56 – 70

15

Turn

71 – 74

4

Beta strand

75 – 82

8

Turn

83 – 85

3

Beta strand

90 – 93

4

Beta strand

105 – 111

7

Beta strand

113 – 120

8

Helix

124 – 140

17

Sequences

	Sequence		Length	Mass (Da)
	O00401 [UniParc]. Last modified February 1, 2005. Version 2. Checksum: B5895C6055E23049	FASTA	505	54,827
	10 20 30 40 50 60 MSSVQQQPPP PRRVTNVGSL LLTPQENESL FTFLGKKCVT MSSAVVQLYA ADRNCMWSKK 70 80 90 100 110 120 CSGVACLVKD NPQRSYFLRI FDIKDGKLLW EQELYNNFVY NSPRGYFHTF AGDTCQVALN 130 140 150 160 170 180 FANEEEAKKF RKAVTDLLGR RQRKSEKRRD PPNGPNLPMA TVDIKNPEIT TNRFYGPQVN 190 200 210 220 230 240 NISHTKEKKK GKAKKKRLTK ADIGTPSNFQ HIGHVGWDPN TGFDLNNLDP ELKNLFDMCG 250 260 270 280 290 300 ISEAQLKDRE TSKVIYDFIE KTGGVEAVKN ELRRQAPPPP PPSRGGPPPP PPPPHNSGPP 310 320 330 340 350 360 PPPARGRGAP PPPPSRAPTA APPPPPPSRP SVAVPPPPPN RMYPPPPPAL PSSAPSGPPP 370 380 390 400 410 420 PPPSVLGVGP VAPPPPPPPP PPPGPPPPPG LPSDGDHQVP TTAGNKAALL DQIREGAQLK 430 440 450 460 470 480 KVEQNSRPVS CSGRDALLDQ IRQGIQLKSV ADGQESTPPT PAPTSGIVGA LMEVMQKRSK 490 500 AIHSSDEDED EDDEEDFEDD DEWED

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of N-WASP homologs in human and rat brain." Fukuoka M., Miki H., Takenawa T. Gene 196:43-48(1997) [PubMed: 9322739] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri." Suzuki T., Miki H., Takenawa T., Sasakawa C. EMBO J. 17:2767-2776(1998) [PubMed: 9582270] [Abstract] Cited for: INTERACTION WITH SHIGELLA FLEXNERI ICSA.
[5]	"Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility." Egile C., Loisel T.P., Laurent V., Li R., Pantaloni D., Sansonetti P.J., Carlier M.-F. J. Cell Biol. 146:1319-1332(1999) [PubMed: 10491394] [Abstract] Cited for: INTERACTION WITH SHIGELLA FLEXNERI ICSA.
[6]	"Phosphorylation of WASP by the Cdc42-associated kinase ACK1: dual hydroxyamino acid specificity in a tyrosine kinase." Yokoyama N., Lougheed J., Miller W.T. J. Biol. Chem. 280:42219-42226(2005) [PubMed: 16257963] [Abstract] Cited for: PHOSPHORYLATION AT SER-242 AND TYR-256 BY TNK2, INTERACTION WITH WASL.
[7]	"NOSTRIN functions as a homotrimeric adaptor protein facilitating internalization of eNOS." Icking A., Matt S., Opitz N., Wiesenthal A., Mueller-Esterl W., Schilling K. J. Cell Sci. 118:5059-5069(2005) [PubMed: 16234328] [Abstract] Cited for: INTERACTION WITH NOSTRIN.
[8]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-256, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[9]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-256, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[10]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484 AND SER-485, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-256, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[12]	"Insulin receptor tyrosine kinase substrate links the E. coli O157:H7 actin assembly effectors Tir and EspF(U) during pedestal formation." Vingadassalom D., Kazlauskas A., Skehan B., Cheng H.C., Magoun L., Robbins D., Rosen M.K., Saksela K., Leong J.M. Proc. Natl. Acad. Sci. U.S.A. 106:6754-6759(2009) [PubMed: 19366662] [Abstract] Cited for: FUNCTION, INTERACTION WITH E.COLI EFFECTOR PROTEIN ESPF(U), IDENTIFICATION IN A COMPLEX WITH BAIAP2L1 AND E.COLI EFFECTOR PROTEIN ESPF(U).
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"The structural basis of actin interaction with multiple WH2/beta-thymosin motif-containing proteins." Aguda A.H., Xue B., Irobi E., Preat T., Robinson R.C. Structure 14:469-476(2006) [PubMed: 16531231] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 451-465.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D88460 mRNA. Translation: BAA20128.1.
AC006333 Genomic DNA. Translation: AAQ96857.1.
BC052955 mRNA. Translation: AAH52955.1.

IPI

IPI00011676.

RefSeq

NP_003932.3. NM_003941.2.

UniGene

Hs.143728.
Hs.83916.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FF3	X-ray	2.00	C	451-465	[»]
2VCP	X-ray	3.20	D/E	392-484	[»]

ProteinModelPortal

O00401.

SMR

O00401. Positions 29-150, 195-253, 403-450, 466-491.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29042N.

IntAct

O00401. 16 interactions.

MINT

MINT-157215.

STRING

O00401.

PTM databases

PhosphoSite

O00401.

Proteomic databases

PRIDE

O00401.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000223023; ENSP00000223023; ENSG00000106299.

GeneID

8976.

KEGG

hsa:8976.

UCSC

uc003vkz.1. human.

Organism-specific databases

CTD

8976.

GeneCards

GC07M123321.

H-InvDB

HIX0007039.

HGNC

HGNC:12735. WASL.

HPA

CAB005399.
HPA005750.

MIM

605056. gene.

neXtProt

NX_O00401.

PharmGKB

PA37346.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG717283.

HOVERGEN

HBG000222.

InParanoid

O00401.

OMA

SAIRSYF.

OrthoDB

EOG4JM7Q1.

PhylomeDB

O00401.

Enzyme and pathway databases

Pathway_Interaction_DB

ephbfwdpathway. EPHB forward signaling.

Reactome

REACT_111045. Developmental Biology.
REACT_111155. Cell-Cell communication.
REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

O00401.

Bgee

O00401.

CleanEx

HS_WASL.

Genevestigator

O00401.

GermOnline

ENSG00000106299. Homo sapiens.

Family and domain databases

InterPro

IPR000697. EVH1.
IPR000095. PAK_box_Rho-bd.
IPR011993. PH_type.
IPR011026. WASP_C.
IPR003124. WH2_actin-bd.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.

KO

K05747.

Pfam

PF00786. PBD. 1 hit.
PF00568. WH1. 1 hit.
PF02205. WH2. 2 hits.
[Graphical view]

SMART

SM00285. PBD. 1 hit.
SM00461. WH1. 1 hit.
SM00246. WH2. 2 hits.
[Graphical view]

SUPFAM

SSF47912. WASP_C. 2 hits.

PROSITE

PS50108. CRIB. 1 hit.
PS50229. WH1. 1 hit.
PS51082. WH2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

NextBio

33689.

SOURCE

Search...

Entry information

Entry name

WASL_HUMAN

Accession

Primary (citable) accession number: O00401
Secondary accession number(s): Q7Z746

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	February 1, 2005
Last modified:	January 25, 2012
This is version 117 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.