Gene Symbol: WASHC2C
Description: WASH complex subunit 2C
Alias: FAM21A, FAM21C, VPEF, WASH complex subunit 2C, WASH complex subunit FAM21C, family with sequence similarity 21 member C, vaccinia virus penetration factor
Species: human
Products:     WASHC2C

Top Publications

  1. Harbour M, Breusegem S, Antrobus R, Freeman C, Reid E, Seaman M. The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics. J Cell Sci. 2010;123:3703-17 pubmed publisher
  2. Jia D, Gomez T, Billadeau D, Rosen M. Multiple repeat elements within the FAM21 tail link the WASH actin regulatory complex to the retromer. Mol Biol Cell. 2012;23:2352-61 pubmed publisher
    ..We propose that multivalency enables FAM21 to sense the density of retromer on membranes, allowing coordination of SHRC recruitment, and consequent actin polymerization, with retromer sorting domain organization/maturation. ..
  3. Gomez T, Billadeau D. A FAM21-containing WASH complex regulates retromer-dependent sorting. Dev Cell. 2009;17:699-711 pubmed publisher
  4. Derivery E, Sousa C, Gautier J, Lombard B, Loew D, Gautreau A. The Arp2/3 activator WASH controls the fission of endosomes through a large multiprotein complex. Dev Cell. 2009;17:712-23 pubmed publisher
    ..Together, these data suggest that the WASH molecular machine, integrating CP with a NPF, controls the fission of endosomes through an interplay between the forces generated by microtubule motors and actin polymerization. ..
  5. Jia D, Gomez T, Metlagel Z, Umetani J, Otwinowski Z, Rosen M, et al. WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes. Proc Natl Acad Sci U S A. 2010;107:10442-7 pubmed publisher
    ..Strumpellin is mutated in the human disease hereditary spastic paraplegia, and its link to WASH suggests that misregulation of actin dynamics on endosomes may play a role in this disorder. ..
  6. Harbour M, Breusegem S, Seaman M. Recruitment of the endosomal WASH complex is mediated by the extended 'tail' of Fam21 binding to the retromer protein Vps35. Biochem J. 2012;442:209-20 pubmed publisher
    ..Additionally, overexpression of the Fam21-tail results in cell-spreading defects, implicating the activity of the WASH complex in regulating the mobilization of membrane into the endosome-to-cell surface pathway. ..
  7. Helfer E, Harbour M, Henriot V, Lakisic G, Sousa Blin C, Volceanov L, et al. Endosomal recruitment of the WASH complex: active sequences and mutations impairing interaction with the retromer. Biol Cell. 2013;105:191-207 pubmed publisher
    ..The interaction between these two endosomal machineries, the WASH complex and the retromer, is likely to play a critical role in forming platforms at the surface of endosomes for efficient sorting of cargoes. ..
  8. Freeman C, Hesketh G, Seaman M. RME-8 coordinates the activity of the WASH complex with the function of the retromer SNX dimer to control endosomal tubulation. J Cell Sci. 2014;127:2053-70 pubmed publisher
  9. Deng Z, Gomez T, Osborne D, Phillips Krawczak C, Zhang J, Billadeau D. Nuclear FAM21 participates in NF-κB-dependent gene regulation in pancreatic cancer cells. J Cell Sci. 2015;128:373-84 pubmed publisher
    ..Thus, FAM21 not only functions as an integral component of the cytoplasmic WASH complex, but also modulates NF-κB gene transcription in the nucleus. ..

More Information


  1. Hernandez Valladares M, Kim T, Kannan B, Tung A, Aguda A, Larsson M, et al. Structural characterization of a capping protein interaction motif defines a family of actin filament regulators. Nat Struct Mol Biol. 2010;17:497-503 pubmed publisher
    ..Peptides comprising these CPI motifs are able to inhibit CP and to uncap CP-bound actin filaments. ..
  2. Vincendeau M, Kramer S, Hadian K, Rothenaigner I, Bell J, Hauck S, et al. Control of HIV replication in astrocytes by a family of highly conserved host proteins with a common Rev-interacting domain (Risp). AIDS. 2010;24:2433-42 pubmed publisher
    ..We conclude that the Risp family represents a novel family of host factors that can control HIV replication and may be important for the containment of HIV infection in brain reservoirs. ..
  3. Zavodszky E, Seaman M, Moreau K, Jimenez Sanchez M, Breusegem S, Harbour M, et al. Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy. Nat Commun. 2014;5:3828 pubmed publisher
    ..Thus, the PD-causing D620N mutation in VPS35 restricts WASH complex recruitment to endosomes, and reveals a novel role for the WASH complex in autophagosome formation. ..
  4. McGough I, Steinberg F, Gallon M, Yatsu A, Ohbayashi N, Heesom K, et al. Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-to-plasma-membrane recycling. J Cell Sci. 2014;127:4940-53 pubmed publisher
    ..Overall, these data reveal hidden complexities in retromer-mediated sorting and open up new directions in our molecular understanding of this essential sorting complex. ..
  5. Huang C, Lu T, Bair C, Chang Y, Jwo J, Chang W. A novel cellular protein, VPEF, facilitates vaccinia virus penetration into HeLa cells through fluid phase endocytosis. J Virol. 2008;82:7988-99 pubmed publisher
    ..Moreover, virus penetration required a novel cellular protein, vaccinia virus penetration factor (VPEF)...
  6. Phillips Krawczak C, Singla A, Starokadomskyy P, Deng Z, Osborne D, Li H, et al. COMMD1 is linked to the WASH complex and regulates endosomal trafficking of the copper transporter ATP7A. Mol Biol Cell. 2015;26:91-103 pubmed publisher
    ..This work provides a mechanistic explanation for the role of COMMD1 in copper homeostasis and uncovers additional genes involved in the regulation of copper transporter recycling. ..
  7. Kramer Hammerle S, Ceccherini Silberstein F, Bickel C, Wolff H, Vincendeau M, Werner T, et al. Identification of a novel Rev-interacting cellular protein. BMC Cell Biol. 2005;6:20 pubmed
    ..4.1 may act as a modulator of Rev activity. The experimental strategies outlined in this study are applicable to the identification and biological characterization of further novel Rev-interacting cellular factors. ..
  8. Follett J, Bugarcic A, Yang Z, Ariotti N, Norwood S, Collins B, et al. Parkinson Disease-linked Vps35 R524W Mutation Impairs the Endosomal Association of Retromer and Induces ?-Synuclein Aggregation. J Biol Chem. 2016;291:18283-98 pubmed publisher