Reviewed, UniProtKB/Swiss-Prot O00401 (WASL_HUMAN)

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.
Sequence processing	The displayed sequence is not processed.
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.
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 the WW domains of PRPF40A/FBP11 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.
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.
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
Gene Ontology (GO)
Biological process	actin polymerization or depolymerization Traceable author statement. Source: ProtInc cell motion Traceable author statement. Source: ProtInc protein complex assembly Traceable author statement. Source: ProtInc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	actin cytoskeleton Traceable author statement. Source: ProtInc cytoplasm Inferred from direct assay. Source: HPA nucleolus Inferred from direct assay. Source: HPA
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
ACTR3	P61157	1	EBI-957615,EBI-351419	From a different organism.
Fnbp1	Q8R511	2	EBI-957615,EBI-1111424	From a different organism.
GRB2	P62993	1	EBI-957615,EBI-401755
LCK	P06239	1	EBI-957615,EBI-1348
NCK1	P16333	1	EBI-957615,EBI-389883
PTPN2	P17706	1	EBI-957615,EBI-984930

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

256

1

Phosphotyrosine Ref.7

Modified residue

484

1

Phosphoserine Ref.8

Modified residue

485

1

Phosphoserine Ref.8

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)
	O00401-1 [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]	"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.
[7]	"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.
[8]	"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.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"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

EMBLGenBankDDBJ

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

IPI

IPI00011676.

RefSeq

NP_003932.3.

UniGene

Hs.143728
Hs.708402
Hs.83916

3D structure databases

PDBPDBe

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

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:29042N.

IntAct

O00401. 8 interactions.

PTM databases

PhosphoSite

O00401.

Proteomic databases

PRIDE

O00401.

Genome annotation databases

Ensembl

ENSG00000106299. Homo sapiens. [Contig view]

GeneID

8976.

KEGG

hsa:8976.

Organism-specific databases

GeneCards

GC07M123109.

H-InvDB

HIX0007039.

HGNC

HGNC:12735. WASL.

HPA

CAB005399.
HPA005750.

MIM

605056. gene.

PharmGKB

PA37346.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O00401.

HOVERGEN

O00401.

OMA

O00401. PTPAGNK.

Enzyme and pathway databases

Pathway_Interaction_DB

ephbfwdpathway. EPHB forward signaling.

Reactome

REACT_12508. Metabolism of nitric oxide.

Gene expression databases

ArrayExpress

O00401.

Bgee

O00401.

CleanEx

HS_WASL.

GermOnline

ENSG00000106299. Homo sapiens.

Family and domain databases

InterPro

IPR000697. EVH1.
IPR000095. PAK_box_Rho_bd.
IPR011993. PH_type.
IPR003124. WH2_actin_bd.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.

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]

PROSITE

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

ProtoNet

Search...

Other Resources

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:	June 16, 2009
This is version 89 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)