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Protein

Putative WAS protein family homolog 3

Gene

WASH3P

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a nucleation-promoting factor at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting (PubMed:18159949, PubMed:20175130). Involved in endocytic trafficking of EGF (PubMed:20175130). Its assembly in the WASH core complex seems to inhibit its NPF activity and via FAM21 is required for its membrane targeting. Involved in transferrin receptor recycling. Regulates the trafficking of endosomal alpha5beta1 integrin to the plasma membrane and involved in invasive cell migration (By similarity). In T-cells involved in endosome-to-membrane recycling of receptors including T-cell receptor (TCR), CD28 and ITGAL; proposed to be implicated in T cell proliferation and effector function. In dendritic cells involved in endosome-to-membrane recycling of major histocompatibility complex (MHC) class II probably involving retromer and subsequently allowing antigen sampling, loading and presentation during T-cell activation. Involved in Arp2/3 complex-dependent actin assembly driving Salmonella typhimurium invasion independent of ruffling (By similarity). Involved in the exocytosis of MMP14 leading to matrix remodeling during invasive migration and implicating late endosome-to-plasma membrane tubular connections and cooperation with the exocyst complex (By similarity). Involved in negative regulation of autophagy independently from its role in endosomal sorting by inhibiting BECN1 ubiquitination to inactivate PIK3C3/Vps34 activity (By similarity).By similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • Arp2/3 complex-mediated actin nucleation Source: UniProtKB
  • early endosome to late endosome transport Source: UniProtKB
  • endosomal transport Source: UniProtKB
  • endosome organization Source: UniProtKB
  • protein targeting to lysosome Source: UniProtKB
  • retrograde transport, endosome to Golgi Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Transport

Keywords - Ligandi

Actin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Putative WAS protein family homolog 3
Alternative name(s):
Protein FAM39DP
Gene namesi
Name:WASH3P
Synonyms:FAM39DP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:24362. WASH3P.

Subcellular locationi

GO - Cellular componenti

  • autophagosome Source: UniProtKB-SubCell
  • centriole Source: UniProtKB-SubCell
  • cytoplasmic vesicle Source: UniProtKB-KW
  • cytosol Source: GOC
  • early endosome Source: UniProtKB
  • early endosome membrane Source: UniProtKB-SubCell
  • filopodium Source: UniProtKB
  • lamellipodium Source: UniProtKB
  • recycling endosome Source: UniProtKB
  • recycling endosome membrane Source: UniProtKB-SubCell
  • WASH complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoplasmic vesicle, Cytoskeleton, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi461 – 4611W → A: No effect on WASH complex assembly. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 463463Putative WAS protein family homolog 3PRO_0000390962Add
BLAST

Proteomic databases

EPDiC4AMC7.
MaxQBiC4AMC7.
PaxDbiC4AMC7.
PRIDEiC4AMC7.

Expressioni

Organism-specific databases

HPAiHPA002689.

Interactioni

Subunit structurei

Component of the WASH core complex also known as WASH regulatory complex SHRC composed of WASH (WASH1, WASH2P or WASH3P), FAM21 (FAM21A or FAM21C), KIAA1033/SWIP, KIAA0196/Strumpellin and CCDC53. The WASH core complex associates with the F-actin-capping protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric manner which was initially described as WASH complex (PubMed:20498093). Interacts (via WHD1 region) with FAM21C; the interaction is direct (By similarity). Interacts with alpha-tubulin. Interacts with BECN1; WASH1 and AMBRA1 can competetively interact with BECN1. Interacts with BLOC1S2; may associate with the BLOC-1 complex. Interacts with tubulin gamma chain (TUBG1 or TUBG2). Interacts with EXOC1, EXOC4, EXOC8; in MMP14-positive endosomes in breast tumor cells; indicative for an association with the exocyst complex (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiC4AMC7. 1 interaction.
STRINGi9606.ENSP00000352498.

Structurei

3D structure databases

ProteinModelPortaliC4AMC7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini359 – 38123WH2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 165165WHD1Add
BLAST
Regioni1 – 5454Required for WASH complex assembly1 PublicationAdd
BLAST
Regioni347 – 463117VCA1 PublicationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi266 – 32863Pro-richAdd
BLAST
Compositional biasi338 – 3458Poly-Ser

Domaini

The VCA (verprolin, cofilin, acidic) domain promotes actin polymerization by the Arp2/3 complex in vitro.2 Publications

Sequence similaritiesi

Belongs to the WASH1 family.Curated
Contains 1 WH2 domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IFZ4. Eukaryota.
ENOG410YN2V. LUCA.
InParanoidiC4AMC7.

Family and domain databases

InterProiIPR021854. WASH1_WAHD.
IPR003124. WH2_dom.
[Graphical view]
PfamiPF11945. WASH_WAHD. 1 hit.
[Graphical view]
PROSITEiPS51082. WH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

C4AMC7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTPVRMQHSL AGQTYAVPLI QPDLRREEAV QQMADALQYL QKVSGDIFSR
60 70 80 90 100
ISQQVEQSRS QVQAIGEKVS LAQAKIEKIK GSKKAIKVFS SAKYPAPERL
110 120 130 140 150
QEYGSIFTGA QDPGLQRRPR HRIQSKHRPL DERALQEKDF PVCVSTKPEP
160 170 180 190 200
EDDAEEGLGG LPSNISSVSS LLLFNTTENL GKKYVFLDPL AGAVTKTHVM
210 220 230 240 250
LGAETEEKLF DAPLSISKRE QLEQQVPENY FYVPDLGQVP EIDVPSYLPD
260 270 280 290 300
LPGITNDLMY IADLGPGIAP SAPGTIPELP TFHTEVAEPL KVDLQDGVLT
310 320 330 340 350
PPPPPPPPPP APEVLASAPP LPPSTAAPVG QGARQDDSSS SASPSVQGAP
360 370 380 390 400
REVVDPSGGR ATLLESIRQA GGIGKAKLRS MKERKLEKKQ QKEQEQVRAT
410 420 430 440 450
SQGGHLMSDL FNKLVMRRKG ISGKGPGAGE GPGGAFARVS DSIPPLPPPQ
460
QPQAEEDEDD WES
Length:463
Mass (Da):49,995
Last modified:November 3, 2009 - v2
Checksum:iFD6B57565AFDAB82
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti54 – 541Q → R in BC048328 (PubMed:15489334).Curated
Sequence conflicti119 – 1191P → S in BC048328 (PubMed:15489334).Curated
Sequence conflicti139 – 1391D → LKY in BC048328 (PubMed:15489334).Curated
Sequence conflicti181 – 1811G → Y in BC048328 (PubMed:15489334).Curated
Sequence conflicti255 – 2551T → A in BC048328 (PubMed:15489334).Curated
Sequence conflicti261 – 2611I → S in BC048328 (PubMed:15489334).Curated
Sequence conflicti292 – 2921V → A in BC048328 (PubMed:15489334).Curated
Sequence conflicti300 – 3001T → TAPP in BC048328 (PubMed:15489334).Curated
Sequence conflicti319 – 3191P → S in BC048328 (PubMed:15489334).Curated
Sequence conflicti381 – 3811M → V in BC048328 (PubMed:15489334).Curated
Sequence conflicti390 – 3901Q → K in BC048328 (PubMed:15489334).Curated
Sequence conflicti405 – 4051H → D in BC048328 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC140725 Genomic DNA. No translation available.
BC048328 mRNA. No translation available.
UniGeneiHs.459573.
Hs.585931.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC140725 Genomic DNA. No translation available.
BC048328 mRNA. No translation available.
UniGeneiHs.459573.
Hs.585931.

3D structure databases

ProteinModelPortaliC4AMC7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiC4AMC7. 1 interaction.
STRINGi9606.ENSP00000352498.

Proteomic databases

EPDiC4AMC7.
MaxQBiC4AMC7.
PaxDbiC4AMC7.
PRIDEiC4AMC7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

GeneCardsiWASH3P.
HGNCiHGNC:24362. WASH3P.
HPAiHPA002689.
neXtProtiNX_C4AMC7.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFZ4. Eukaryota.
ENOG410YN2V. LUCA.
InParanoidiC4AMC7.

Miscellaneous databases

PROiC4AMC7.

Family and domain databases

InterProiIPR021854. WASH1_WAHD.
IPR003124. WH2_dom.
[Graphical view]
PfamiPF11945. WASH_WAHD. 1 hit.
[Graphical view]
PROSITEiPS51082. WH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "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].
    Tissue: Brain.
  3. Cited for: GENE DUPLICATION, FUNCTION, DOMAIN, SUBCELLULAR LOCATION.
  4. "Human subtelomeric WASH genes encode a new subclass of the WASP family."
    Linardopoulou E.V., Parghi S.S., Friedman C., Osborn G.E., Parkhurst S.M., Trask B.J.
    PLoS Genet. 3:E237-E237(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: GENE DUPLICATION.
  5. "WASH and the Arp2/3 complex regulate endosome shape and trafficking."
    Duleh S.N., Welch M.D.
    Cytoskeleton 67:193-206(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  6. "WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes."
    Jia D., Gomez T.S., Metlagel Z., Umetani J., Otwinowski Z., Rosen M.K., Billadeau D.D.
    Proc. Natl. Acad. Sci. U.S.A. 107:10442-10447(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT, FUNCTION OF THE WASH CORE COMPLEX, MUTAGENESIS OF TRP-461, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiWASH3_HUMAN
AccessioniPrimary (citable) accession number: C4AMC7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 19, 2010
Last sequence update: November 3, 2009
Last modified: June 8, 2016
This is version 48 of the entry and version 2 of the sequence. [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

Miscellaneous

WASH genes duplicated to multiple chromosomal ends during primate evolution, with highest copy number reached in humans, whose WASH repertoires probably vary extensively among individuals (PubMed:18159949). It is therefore difficult to determine which gene is functional or not. The telomeric region of chromosome 9p is paralogous to the pericentromeric regions of chromosome 9 as well as to 2q. Paralogous regions contain 7 transcriptional units. Duplicated WASH genes are also present in the Xq/Yq pseudoautosomal region, as well as on chromosome 1 and 15. The chromosome 16 copy seems to be a pseudogene.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.