WASHC1

Domain

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

Function

Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) 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:19922874, PubMed:19922875, PubMed:20498093, PubMed:23452853). Involved in endocytic trafficking of EGF (By similarity). Involved in transferrin receptor recycling. Regulates the trafficking of endosomal alpha5beta1 integrin to the plasma membrane and involved in invasive cell migration (PubMed:22114305). 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 (By similarity). 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 (PubMed:24344185). Involved in negative regulation of autophagy independently from its role in endosomal sorting by inhibiting BECN1 ubiquitination to inactivate PIK3C3/Vps34 activity (By similarity).

Post-translational modifications

Ubiquitinated at Lys-220 via 'Lys-63'-linked ubiquitin chains by the TRIM27:MAGEL2 E3 ubiquitin ligase complex, leading to promote endosomal F-actin assembly.

Sequence Similarities

Belongs to the WASH1 family.

Cellular localization

• Early endosome membrane
• Recycling endosome membrane
• Late endosome
• Cytoplasmic vesicle
• Autophagosome
• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Centriole
• Localization to the endosome membrane is mediated via its interaction with WASHC2 (PubMed:19922874). Localizes to MMP14-positive late endosomes and transiently to invadipodia (PubMed:24344185). Localized to Salmonella typhimurium entry sites (By similarity).

Alternative names

FAM39E, WASH1, WASHC1, WASH complex subunit 1, CXYorf1-like protein on chromosome 9, Protein FAM39E, WAS protein family homolog 1

Database links

swissprot:A8K0Z3 entrezGene:100287171 omim:613632 entrezGene:68767