FAM21C - WASH complex subunit FAM21C - human protein (Function)
 
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FAM21C »  WASH complex subunit FAM21C
 
Protein also known as:  Vaccinia virus penetration factor (VPEF).
Gene name:  FAM21C
Family name: FAM21
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Acts at least in part as component of the WASH core complex whose assembly at the surface of endosomes inhibits WASH nucleation-promoting factor (NPF) activity in recruiting and activating the Arp2/3 complex to induce actin polymerization and is involved in the fission of tubules that serve as transport intermediates during endosome sorting. Mediates the recruitment of the WASH core complex to endosome membranes via binding to phospholipids and VPS35 of the retromer CSC. Mediates the recruitment of the F-actin-capping protein dimer to the WASH core complex probably promoting localized F-actin polymerization needed for vesicle scission (PubMed19922874, PubMed20498093, PubMed22513087, PubMed23331060). Via its C-terminus binds various phospholipids, most strongly phosphatidylinositol 4-phosphate (PtdIns-(4)P), phosphatidylinositol 5-phosphate (PtdIns-(5)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2). Involved in the endosome-to-plasma membrane trafficking and recycling of SNX27-retromer-dependent cargo proteins, such as GLUT1 (PubMed25278552). Required for the association of DNAJC13, SDCCAG3, ANKRD50 with retromer CSC subunit VPS35 (PubMed24980502). Required for the endosomal recruitment of CCC complex subunits COMMD1, CCDC93 AND C16orf62 (PubMed25355947). Plays a role in fluid-phase endocytosis, a process exploited by vaccinia intracellular mature virus (IMV) to enter cells. As a result, may facilitate the penetration of IMV into cells (PubMed18550675).  
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  • UniProtKB
GO molecular function 
Phosphatidylinositol-3,4,5-trisphosphate bindingdefinition[GO:0005547]  
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Phosphatidylinositol-3,4-bisphosphate bindingdefinition[GO:0043325]  
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  • UniProtKB
Phosphatidylinositol-3,5-bisphosphate bindingdefinition[GO:0080025]  
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  • UniProtKB
Phosphatidylinositol-3-phosphate bindingdefinition[GO:0032266]  
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  • UniProtKB
Phosphatidylinositol-4,5-bisphosphate bindingdefinition[GO:0005546]  
1
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Phosphatidylinositol-4-phosphate bindingdefinition[GO:0070273]  
1
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Phosphatidylinositol-5-phosphate bindingdefinition[GO:0010314]  
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Protein bindingdefinition[GO:0005515]  
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GO biological process 
Negative regulation of barbed-end actin filament cappingdefinition[GO:2000813]  
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Protein transportdefinition[GO:0015031]  
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  • UniProtKB KW
Regulation of substrate adhesion-dependent cell spreadingdefinition[GO:1900024]  
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  • UniProtKB
Retrograde transport, endosome to Golgidefinition[GO:0042147]  
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Retrograde transport, endosome to plasma membranedefinition[GO:1990126]  
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Note 
In human, FAM21 has undergone evolutionary duplication, with 4 highly homologous family members existing, including FAM21A, FAM21B, FAM21C, and an N-terminally truncated FAM21D form.  
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  • UniProtKB
Caution 
A FAM21C construct with FAM21A-specific sequence insertions of 2 aa and 21 aa resulting in a construct length of 1341 aa similar to FAM21A length has been used for a number of experiments; a part of this construct covering the FAM21A-specific 21 aa insert has been used to produce an anti-FAM21 antibody (PubMed:19922874, PubMed:22513087, PubMed:20498093).  
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  • UniProtKB
The function of the WASH complex is debated. One study using partially purified samples reported a nucleation-promoting factor (NPF) activity (PubMed:19922875). In another study, the reconstituted and highly purified recombinant WASH core complex did not show activity toward Arp2/3 complex suggesting a rather inhibitory role towards WASH NPF activity (PubMed:20498093).  
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Keywords

Biological process 
Protein transport  definition   [KW-0653]
Transport  definition   [KW-0813]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: FAM21C
GenomeRNAi: 253725
PRO: PR:Q9Y4E1