Methylosome protein 50 (WDR77)
The protein contains 342 amino acids for an estimated molecular weight of 36724 Da.
Non-catalytic component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins and histones (PubMed:11756452). This modification targets Sm proteins to the survival of motor neurons (SMN) complex for assembly into small nuclear ribonucleoprotein core particles. Might play a role in transcription regulation. The methylosome complex also methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (PubMed:23071334). (updated: May 23, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs7416672 |
Biological Process
Chromatin organization
Gene expression
NcRNA metabolic process
Negative regulation of epithelial cell proliferation involved in prostate gland development
Pole plasm assembly
Positive regulation of cell population proliferation
Regulation of transcription by RNA polymerase II
Secretory columnal luminar epithelial cell differentiation involved in prostate glandular acinus development
Spliceosomal snRNP assembly
The reference OMIM entry for this protein is 611734
Wd repeat-containing protein 77; wdr77
Methylosome protein, 50-kd; mep50
Androgen receptor-associated protein, 44-kd; p44
DESCRIPTION
WDR77 is a component of the 20S PRMT5 (604045)-containing methyltransferase complex, which modifies specific arginines to dimethylarginines in several spliceosomal Sm proteins (see 601061). This modification targets Sm proteins to the survival of motor neurons (SMN) complex (see 600354) for assembly into small nuclear ribonucleoprotein core particles (Friesen et al., 2002).CLONING
By peptide sequencing of a protein associated with the 20S methyltransferase complex, followed by database analysis, Friesen et al. (2002) obtained a full-length clone encoding WDR77, which they called MEP50. The deduced 342-amino acid protein has 6 WD repeats and has a calculated molecular mass of 36.7 kD. By SDS-PAGE, MEP50 had an apparent molecular mass of 50 kD. Using biochemical cellular fractionation and immunofluorescence analysis, Licciardo et al. (2003) showed that MEP50 localized to both the nucleus and cytoplasm in human cells. Liang et al. (2007) showed that PRMT5 and WDR77, which they called p44, were expressed predominantly as nuclear proteins in fetal Leydig cells and adult human testis, whereas they were predominantly cytoplasmic in fetal germ cells.GENE FUNCTION
Friesen et al. (2002) showed that endogenous MEP50 associated with PRMT5 in the 20S arginine methyltransferase complex in HeLa cells. Protein pull-down assays revealed that MEP50 specifically interacted with SmB (SNRPB; 182282) and SmD2 (SNRPD2; 601061) and more weakly with SmD3 (SNRPD3; 601062) and SmE (SNRPE; 128260). Antibodies directed against MEP50 significantly reduced the arginine methyltransferase activity of the immunopurified complex toward Sm substrates. FCP1 (CTDP1; 604927) is a phosphatase specific for the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A; 180660), which is cyclically phosphorylated during RNA polymerase II transcription. Licciardo et al. (2003) found that FCP1-affinity purified complexes in an FCP1-expressing human lung carcinoma cell line (H1299) contained MEP50 and RNA polymerase II. Glycerol gradient fractionation and Western blot analysis of H1299 whole cell extracts detected MEP50 in protein complexes of 400 kD and more than 800 kD. In nuclear extracts, MEP50 was associated only with the 400-kD complex, which also appeared to contain FCP1 and was distinct from the larger methyltransferase complex containing PRMT5. SUZ12 (606245) belongs to the polycomb group of proteins, which mediate chromatin modification and epigenetic repression of gene expression. Using yeast 2-hybrid, coimmunoprecipitation, and protein pull-down analyses, Furuno et al. (2006) found that SUZ12 interacted with mouse and human MEP50. Human MEP50 interacted with free histone H2a (see 601772) from calf thymus, but not with other histones or with H2A complexed in isolated HeLa cell nucleosomes. PRMT5-mediated transcriptional repression of a reporter gene was dependent on MEP50. Furuno et al. (2006) concluded that MEP50 may be an adaptor between PRMT5 and its H2A substrate and that SUZ12 may have a role in transcriptional regulation through physical interaction with MEP50. Using in vitro assays and in vivo tumor xenograft experiments, Peng et al. (2008) showed that nuclear human p44 inhibits prostate cancer (see 176807) growth, at least in part, through the regulation of cell cycle regulatory genes that include p21 (CDKN1A; 116899). Conversely, cytoplasmic p44 promoted prostate cancer growth through upregulation of ... More on the omim web site
May 26, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 611734 was added.