Q6VEQ5 · WASH2_HUMAN
- ProteinWAS protein family homolog 2
- GeneWASH2P
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids465 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
Function
function
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. Involved in endocytic trafficking of EGF. Involved in transferrin receptor recycling. Regulates the trafficking of endosomal alpha5beta1 integrin to the plasma membrane and involved in invasive cell migration. 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. 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. Involved in negative regulation of autophagy independently from its role in endosomal sorting by inhibiting BECN1 ubiquitination to inactivate PIK3C3/Vps34 activity (By similarity).
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
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
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | autophagosome | |
Cellular Component | centriole | |
Cellular Component | cytosol | |
Cellular Component | early endosome | |
Cellular Component | early endosome membrane | |
Cellular Component | late endosome | |
Cellular Component | recycling endosome | |
Cellular Component | recycling endosome membrane | |
Cellular Component | WASH complex | |
Molecular Function | actin binding | |
Molecular Function | alpha-tubulin binding | |
Molecular Function | gamma-tubulin binding | |
Biological Process | Arp2/3 complex-mediated actin nucleation | |
Biological Process | endocytic recycling | |
Biological Process | endosomal transport | |
Biological Process | exocytosis | |
Biological Process | protein transport | |
Biological Process | regulation of Arp2/3 complex-mediated actin nucleation | |
Biological Process | retrograde transport, endosome to Golgi |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameWAS protein family homolog 2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6VEQ5
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localization to the endosome membrane is mediated via its interaction with WASHC2.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), cross-link.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000257971 | 1-465 | UniProt | WAS protein family homolog 2 | |||
Sequence: MTPVRMQHSLAGQTYAVPLIQPDLRREEAVQQMADALQYLQKVSGDIFSRISQQVEQSRSQVQAIGEKVSLAQAKIEKIKGSKKAIKVFSSAKYPAPERLQEYGSIFTGAQDPGLQRRPRHRIQSKHRPLDERALQEKLKDFPVCVSTKPEPEDDAEEGLGGLPSNISSVSSLLLFNTTENLYKKYVFLDPLAGAVTKTHVMLGAETEEKLFDAPLSISKREQLEQQVPENYFYVPDLGQVPEIDVPSYLPDLPGIANDLMYIADLGPGIAPSAPGTIPELPTFHTEVAEPLKVDLQDGVLTPPPPPPPPPPAPEVLASAPPLPPSTAAPVGQGARQDDSSSSASPSVQGAPREVVDPSGGRATLLESIRQAGGIGKAKLRSMKERKLEKKKQKEQEQVRATSQGGHLMSDLFNKLVMRRKGISGKGPGAGEGPGGAFARVSDSIPPLPPPQQPQAEEDEDDWES | |||||||
Modified residue (large scale data) | 217 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 219 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Cross-link | 220 | UniProt | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 340 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 345 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 368 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Component of the WASH core complex also described as WASH regulatory complex (SHRC) composed of WASH (WASHC1, WASH2P or WASH3P), WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5. 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. Interacts (via WHD1 region) with WASHC2C; the interaction is direct. Interacts with alpha-tubulin. Interacts with BECN1; WASHC1 and AMBRA1 can competitively 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).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-54 | Required for WASH complex assembly | ||||
Sequence: MTPVRMQHSLAGQTYAVPLIQPDLRREEAVQQMADALQYLQKVSGDIFSRISQQ | ||||||
Region | 1-167 | WHD1 | ||||
Sequence: MTPVRMQHSLAGQTYAVPLIQPDLRREEAVQQMADALQYLQKVSGDIFSRISQQVEQSRSQVQAIGEKVSLAQAKIEKIKGSKKAIKVFSSAKYPAPERLQEYGSIFTGAQDPGLQRRPRHRIQSKHRPLDERALQEKLKDFPVCVSTKPEPEDDAEEGLGGLPSNI | ||||||
Region | 297-407 | Disordered | ||||
Sequence: QDGVLTPPPPPPPPPPAPEVLASAPPLPPSTAAPVGQGARQDDSSSSASPSVQGAPREVVDPSGGRATLLESIRQAGGIGKAKLRSMKERKLEKKKQKEQEQVRATSQGGH | ||||||
Compositional bias | 300-328 | Pro residues | ||||
Sequence: VLTPPPPPPPPPPAPEVLASAPPLPPSTA | ||||||
Compositional bias | 333-349 | Polar residues | ||||
Sequence: QGARQDDSSSSASPSVQ | ||||||
Region | 349-465 | VCA | ||||
Sequence: QGAPREVVDPSGGRATLLESIRQAGGIGKAKLRSMKERKLEKKKQKEQEQVRATSQGGHLMSDLFNKLVMRRKGISGKGPGAGEGPGGAFARVSDSIPPLPPPQQPQAEEDEDDWES | ||||||
Domain | 361-383 | WH2 | ||||
Sequence: GRATLLESIRQAGGIGKAKLRSM | ||||||
Compositional bias | 379-398 | Basic and acidic residues | ||||
Sequence: KLRSMKERKLEKKKQKEQEQ | ||||||
Region | 422-465 | Disordered | ||||
Sequence: GISGKGPGAGEGPGGAFARVSDSIPPLPPPQQPQAEEDEDDWES |
Domain
The VCA (verprolin, cofilin, acidic) domain promotes actin polymerization by the Arp2/3 complex in vitro.
Sequence similarities
Belongs to the WASH1 family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length465
- Mass (Da)50,312
- Last updated2010-01-19 v2
- Checksum54FD1BB405E391DF
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 300-328 | Pro residues | ||||
Sequence: VLTPPPPPPPPPPAPEVLASAPPLPPSTA | ||||||
Compositional bias | 333-349 | Polar residues | ||||
Sequence: QGARQDDSSSSASPSVQ | ||||||
Compositional bias | 379-398 | Basic and acidic residues | ||||
Sequence: KLRSMKERKLEKKKQKEQEQ |
Keywords
- Technical term