Q9Y6W5 (WASF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Wiskott-Aldrich syndrome protein family member 2
Short name=WASP family protein member 2

Alternative name(s):
Protein WAVE-2
Verprolin homology domain-containing protein 2

Gene names

Name:	WASF2
Synonyms:	WAVE2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	498 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex. Ref.1 Ref.9
Subunit structure	Binds actin and the Arp2/3 complex. Interacts with BAIAP2. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 and WASF2/WAVE2. Directly interacts with BRK1. Ref.1 Ref.5 Ref.6 Ref.7 Ref.9
Subcellular location	Cytoplasm › cytoskeleton By similarity. Cell projection › lamellipodium By similarity. Note: At the interface between the lamellipodial actin meshwork and the membrane By similarity.
Tissue specificity	Expressed in all tissues with strongest expression in placenta, lung, and peripheral blood leukocytes, but not in skeletal muscle. Ref.1
Domain	Binds and activates the Arp2/3 complex via the C-terminal domain. Interacts with actin via the WH2 domain. Ref.1 Ref.9
Sequence similarities	Belongs to the SCAR/WAVE family. Contains 1 WH2 domain.

Ontologies

Keywords
Cellular component	Cell projection Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing
Ligand	Actin-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Rac protein signal transduction Inferred from electronic annotation. Source: Compara actin cytoskeleton organization Traceable author statement PubMed 9732292. Source: ProtInc actin filament-based movement Inferred from electronic annotation. Source: Compara adenylate cyclase-modulating G-protein coupled receptor signaling pathway Traceable author statement PubMed 9732292. Source: ProtInc ameboidal cell migration Inferred from electronic annotation. Source: Compara angiogenesis Inferred from electronic annotation. Source: Compara endocytosis Inferred from electronic annotation. Source: Compara lamellipodium assembly Inferred from electronic annotation. Source: Compara
Cellular_component	actin cytoskeleton Traceable author statement PubMed 10970852. Source: ProtInc early endosome Inferred from electronic annotation. Source: Compara lamellipodium Inferred from direct assay PubMed 17101133. Source: MGI ruffle Inferred from electronic annotation. Source: Compara
Molecular_function	actin binding Traceable author statement PubMed 10970852. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BAIAP2	Q9UQB8-4	5	EBI-4290615,EBI-6174091

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y6W5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9Y6W5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     275-281: SYPVDNQ → RFSAAQG
     282-498: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 498

498

Wiskott-Aldrich syndrome protein family member 2

PRO_0000188994

Regions

Domain

436 – 453

18

WH2

Compositional bias

268 – 271

4

Poly-Pro

Compositional bias

318 – 328

11

Poly-Pro

Compositional bias

333 – 338

6

Poly-Pro

Compositional bias

347 – 350

4

Poly-Pro

Compositional bias

364 – 371

8

Poly-Pro

Compositional bias

379 – 382

4

Poly-Pro

Compositional bias

391 – 406

16

Poly-Pro

Natural variations

Alternative sequence

275 – 281

7

SYPVDNQ → RFSAAQG in isoform 2.

VSP_042514

Alternative sequence

282 – 498

217

Missing in isoform 2.

VSP_042515

Experimental info

Mutagenesis

40

1

L → D: Decreased interaction with WAVE complex; when associated with D-51. Ref.7

Mutagenesis

50

1

I → D: Decreased interaction with WAVE complex; when associated with D-54. Ref.7

Mutagenesis

51

1

F → D: Decreased interaction with WAVE complex; when associated with D-40. Ref.7

Mutagenesis

54

1

L → D: Decreased interaction with WAVE complex; when associated with D-50. Ref.7

Mutagenesis

124

1

Y → D: Constitutive induction of the formation of actin filaments. Strongly enhances formation of lamellipodia. Ref.9

Mutagenesis

150

1

Y → D: Constitutive induction of the formation of actin filaments. Strongly enhances formation of lamellipodia. Ref.9

Mutagenesis

160 – 161

2

WK → ED: Constitutive induction of the formation of actin filaments. Strongly enhances formation of lamellipodia.

Secondary structure

1

.

.

.

498

Helix Strand Turn

Details...

Helix

436 – 446

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 2005. Version 3. Checksum: C737CE963016DE94	FASTA	498	54,284
	10 20 30 40 50 60 MPLVTRNIEP RHLCRQTLPS VRSELECVTN ITLANVIRQL GSLSKYAEDI FGELFTQANT 70 80 90 100 110 120 FASRVSSLAE RVDRLQVKVT QLDPKEEEVS LQGINTRKAF RSSTIQDQKL FDRNSLPVPV 130 140 150 160 170 180 LETYNTCDTP PPLNNLTPYR DDGKEALKFY TDPSYFFDLW KEKMLQDTKD IMKEKRKHRK 190 200 210 220 230 240 EKKDNPNRGN VNPRKIKTRK EEWEKMKMGQ EFVESKEKLG TSGYPPTLVY QNGSIGCVEN 250 260 270 280 290 300 VDASSYPPPP QSDSASSPSP SFSEDNLPPP PAEFSYPVDN QRGSGLAGPK RSSVVSPSHP 310 320 330 340 350 360 PPAPPLGSPP GPKPGFAPPP APPPPPPPMI GIPPPPPPVG FGSPGTPPPP SPPSFPPHPD 370 380 390 400 410 420 FAAPPPPPPP PAADYPTLPP PPLSQPTGGA PPPPPPPPPP GPPPPPFTGA DGQPAIPPPL 430 440 450 460 470 480 SDTTKPKSSL PAVSDARSDL LSAIRQGFQL RRVEEQREQE KRDVVGNDVA TILSRRIAVE 490 YSDSEDDSSE FDEDDWSD
	Isoform 2 [UniParc]. Checksum: C5E79110854FAF56	FASTA	281	31,979
	10 20 30 40 50 60 MPLVTRNIEP RHLCRQTLPS VRSELECVTN ITLANVIRQL GSLSKYAEDI FGELFTQANT 70 80 90 100 110 120 FASRVSSLAE RVDRLQVKVT QLDPKEEEVS LQGINTRKAF RSSTIQDQKL FDRNSLPVPV 130 140 150 160 170 180 LETYNTCDTP PPLNNLTPYR DDGKEALKFY TDPSYFFDLW KEKMLQDTKD IMKEKRKHRK 190 200 210 220 230 240 EKKDNPNRGN VNPRKIKTRK EEWEKMKMGQ EFVESKEKLG TSGYPPTLVY QNGSIGCVEN 250 260 270 280 VDASSYPPPP QSDSASSPSP SFSEDNLPPP PAEFRFSAAQ G

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of two human WAVE/SCAR homologues as general actin regulatory molecules which associate with the Arp2/3 complex." Suetsugu S., Miki H., Takenawa T. Biochem. Biophys. Res. Commun. 260:296-302(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH ACTIN AND THE ARP2/3 COMPLEX, SUBUNIT, DOMAIN, TISSUE SPECIFICITY. Tissue: T-cell lymphoma.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lymph.
[5]	"IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling." Miki H., Yamaguchi H., Suetsugu S., Takenawa T. Nature 408:732-735(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BAIAP2.
[6]	"Purification and architecture of the ubiquitous Wave complex." Gautreau A., Ho H.-Y., Li J., Steen H., Gygi S.P., Kirschner M.W. Proc. Natl. Acad. Sci. U.S.A. 101:4379-4383(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH C3ORF10.
[7]	"Structure and control of the actin regulatory WAVE complex." Chen Z., Borek D., Padrick S.B., Gomez T.S., Metlagel Z., Ismail A.M., Umetani J., Billadeau D.D., Otwinowski Z., Rosen M.K. Nature 468:533-538(2010) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LEU-40; ILE-50; PHE-51 AND LEU-54, SUBUNIT.
[8]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly." Chereau D., Kerff F., Graceffa P., Grabarek Z., Langsetmo K., Dominguez R. Proc. Natl. Acad. Sci. U.S.A. 102:16644-16649(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 433-464 IN COMPLEX WITH ACTIN, FUNCTION, DOMAIN, MUTAGENESIS OF TYR-124; TYR-150 AND 160-TRP-LYS-161, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB026542 mRNA. Translation: BAA81795.1.
AK303011 mRNA. Translation: BAG64142.1.
AL096774 Genomic DNA. Translation: CAC18518.1.
AL663122 Genomic DNA. No translation available.
BX293535 Genomic DNA. No translation available.
BC040943 mRNA. Translation: AAH40943.1.

IPI

IPI00472164.
IPI00976656.

RefSeq

NP_001188333.1. NM_001201404.1.
NP_008921.1. NM_006990.3.

UniGene

Hs.469244.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2A40	X-ray	1.80	C/F	433-464	[»]

ProteinModelPortal

Q9Y6W5.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9Y6W5. 2 interactions.

MINT

MINT-5005787.

STRING

9606.ENSP00000396211.

PTM databases

PhosphoSite

Q9Y6W5.

Polymorphism databases

DMDM

59800456.

Proteomic databases

PaxDb

Q9Y6W5.

PeptideAtlas

Q9Y6W5.

PRIDE

Q9Y6W5.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000430629; ENSP00000396211; ENSG00000158195.
ENST00000536657; ENSP00000439883; ENSG00000158195.

GeneID

10163.

KEGG

hsa:10163.

UCSC

uc001bof.2. human.

Organism-specific databases

CTD

10163.

GeneCards

GC01M027730.

HGNC

HGNC:12733. WASF2.

HPA

CAB022632.

MIM

605875. gene.

neXtProt

NX_Q9Y6W5.

PharmGKB

PA37344.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG299696.

HOGENOM

HOG000021456.

HOVERGEN

HBG058482.

InParanoid

Q9Y6W5.

KO

K05748.

OMA

VASANNT.

OrthoDB

EOG49W2GB.

PhylomeDB

Q9Y6W5.

Gene expression databases

ArrayExpress

Q9Y6W5.

Bgee

Q9Y6W5.

CleanEx

HS_WASF2.

Genevestigator

Q9Y6W5.

GermOnline

ENSG00000158195. Homo sapiens.

Family and domain databases

InterPro

IPR003124. WH2_dom.
[Graphical view]

Pfam

PF02205. WH2. 1 hit.
[Graphical view]

SMART

SM00246. WH2. 1 hit.
[Graphical view]

PROSITE

PS51082. WH2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

WASF2. human.

EvolutionaryTrace

Q9Y6W5.

GenomeRNAi

10163.

NextBio

38478.

PMAP-CutDB

Q9Y6W5.

SOURCE

Search...

Entry information

Entry name

WASF2_HUMAN

Accession

Primary (citable) accession number: Q9Y6W5
Secondary accession number(s): B4DZN0, O60794, Q9UDY7

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	February 1, 2005
Last modified:	May 1, 2013
This is version 116 of the entry and version 3 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.