Alternative titles; symbolsTRANSMEMBRANE PROTEIN 113; TMEM113HGNC Approved Gene Symbol: WDR82Cytogenetic location: 3p21.2 Genomic coordinates (GRCh38): 3:52,...
Alternative titles; symbols
HGNC Approved Gene Symbol: WDR82
Cytogenetic location: 3p21.2 Genomic coordinates (GRCh38): 3:52,254,423-52,278,648 (from NCBI)
WDR82 is a regulatory component of the mammalian SET1A (611052) and SET1B (611055) histone H3 (see 602810) lys4 methyltransferase complexes (Lee and Skalnik, 2005; Lee et al., 2007). WDR82 additionally associates with multiple protein complexes, including a chaperonin-containing TCP1 (186980) complex and a protein phosphatase-1 (PP1; see 176875) complex (Lee et al., 2010).
▼ Cloning and Expression
In their Figure 3, Lee et al. (2010) showed that the WDR82 protein contains 7 WD40 domains distributed throughout the molecule.
Scott (2007) mapped the TMEM113 gene to chromosome 3p21.1 based on an alignment of the TMEM113 sequence (GenBank AC092045) with the genomic sequence (build 36.2).
▼ Gene Function
By mass spectrometric analysis of nuclear proteins that immunoprecipitated with WDR82 from HEK293 cell nuclear extracts, Lee et al. (2010) identified WDR82 as a component of several protein complexes, including 4 distinct histone H3 lys4 methyltransferase complexes, a chaperonin-containing TCP1 complex, and a PP1 complex. They characterized the PP1 complex further and found that it contained PNUTS (PPP1R10; 603771), TOX4 (614032), WDR82, and any 1 of the 3 catalytic subunits of PP1, PP1-alpha (PPP1CA; 176875), PP1-beta (PPP1CB; 600590), or PP1-gamma (PPP1CC; 176914). The complex, which they called PTW/PP1, had an apparent molecular mass of about 200 kD, suggesting that it contains 1 molecule of each subunit. Mutation analysis revealed that human WDR82 interacted with a central domain of mouse Pnuts. WDR82 did not interact directly with any other human PTW/PP1 subunit. The PTW/PP1 complex efficiently dephosphorylated the isolated C-terminal domain of the large subunit of mouse RNA polymerase II (POLR2A; 180660) in vitro. The PTW/PP1 complex was stable throughout the cell cycle in HEK293 cells, but its association with chromatin was regulated. PTW/PP1 associated with chromatin during interphase, was excluded from condensed chromosomes during early mitosis, and was reloaded onto chromosomes at late telophase.
Using coimmunoprecipitation analysis, Austenaa et al. (2021) identified ZC3H4 and WDR82 as interacting partners in mouse bone marrow-derived macrophages and HeLa cells. WDR82 and ZC3H4 interacted through the C terminus of ZC3H4 to form a complex that functioned as a repressor of extragenic transcription. Chromatin immunoprecipitation-sequencing analysis showed that the genomic distribution of Wdr82 and Zc3h4 overlapped and that both proteins were recruited to sites of high RNA polymerase II occupancy in mouse macrophages. Further analysis in mouse macrophages and HeLa cells demonstrated that WDR82 and ZC3H4 suppressed long noncoding RNAs (lncRNAs) transcribed from cis-regulatory elements, such as enhancers and promoters, and that transcription termination by the complex required the first exon of those lncRNAs.