Protein arginine N-methyltransferase 5 (PRMT5)
The protein contains 637 amino acids for an estimated molecular weight of 72684 Da.
Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503, PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653, PubMed:21258366, PubMed:21917714, PubMed:22269951, PubMed:21081503). Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles (PubMed:12411503, PubMed:11747828, PubMed:17709427). Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890). Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development (By similarity). Methylates histone H3 'Arg-8', which may repress transcription (By similarity). 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 (By similarity). Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylate (updated: April 7, 2021)
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.
(right-click above to access to more options from the contextual menu)
Biological Process
Cell population proliferation
Chromatin organization
Circadian regulation of gene expression
DNA-templated transcription, termination
Endothelial cell activation
Gene expression
Golgi ribbon formation
Histone arginine methylation
Histone H4-R3 methylation
Liver regeneration
NcRNA metabolic process
Negative regulation of cell differentiation
Negative regulation of transcription by RNA polymerase II
Peptidyl-arginine methylation
Peptidyl-arginine methylation, to symmetrical-dimethyl arginine
Peptidyl-arginine N-methylation
Positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway
Positive regulation of oligodendrocyte differentiation
Regulation of DNA methylation
Regulation of ERK1 and ERK2 cascade
Regulation of mitotic nuclear division
Regulation of signal transduction by p53 class mediator
Regulation of transcription, DNA-templated
Spliceosomal snRNP assembly
Transcription, DNA-templated
Cellular Component
Chromatin
Cytoplasm
Cytosol
Golgi apparatus
Histone methyltransferase complex
Methylosome
Nucleoplasm
Nucleus
Protein complex
Molecular Function
Chromatin binding
Core promoter sequence-specific DNA binding
E-box binding
Histone methyltransferase activity (H4-R3 specific)
Histone-arginine N-methyltransferase activity
Identical protein binding
Methyl-CpG binding
Methyltransferase activity
P53 binding
Protein complex binding
Protein heterodimerization activity
Protein-arginine N-methyltransferase activity
Protein-arginine omega-N symmetric methyltransferase activity
Ribonucleoprotein complex binding
Transcription corepressor activity
The reference OMIM entry for this protein is 604045
Protein arginine methyltransferase 5; prmt5
Shk1 kinase-binding protein 1, s. pombe, homolog of; skb1
Icln-binding protein, 72-kd; ibp72
Jak-binding protein 1; jbp1
Histone synthetic lethal 7, s. cerevisiae, homolog of; hsl7
DESCRIPTION
PRMT5 belongs to the methyltransferase enzyme family. Methyltransferases transfer methyl groups from S-adenosylmethionine (AdoMet) to a variety of substrates, including nucleic acids, small molecules, and proteins (summary by Pollack et al., 1999).CLONING
The S. pombe Shk1 gene is a PAK (see 602590) homolog that is essential for cell viability and that plays key roles in morphologic control and mating response pathways. The Skb1 protein is a regulator of Shk1 that appears to positively modulate Shk1 function. Gilbreth et al. (1996) identified partial cDNAs encoding a human Skb1 homolog. Gilbreth et al. (1998) isolated additional clones corresponding to the complete coding region of human SKB1. The predicted 637-amino acid human protein shares 39% identity with S. pombe Skb1. Independently, Krapivinsky et al. (1998) identified SKB1 as a 72-kD protein that coimmunoprecipitated with the ICln (602158) chloride channel and was thus termed IBP72 (ICln-binding protein of 72 kD). Northern blot analysis revealed that the IBP72 gene was widely expressed as a 2.4-kb transcript. The authors suggested that ICln is not a channel itself but rather part of a pathway that is connected to a chloride current, possibly through cytoskeletal rearrangement. IBP72 may provide a link between ICln and cytoskeletal rearrangement because PAKs, such as Shk1, affect cell morphology through interactions with the cytoskeleton. Using mouse Jak2 (147796) as bait in a yeast 2-hybrid screen of a HeLa cell cDNA library, Pollack et al. (1999) cloned PRMT5, which they called JBP1. The deduced 637-amino acid protein has a calculated molecular mass of 72.4 kD. JBP1 contains 3 motifs characteristic of methyltransferases, including a conserved GxGxG motif (GAGRG) within the predicted AdoMet-binding pocket. Northern blot analysis detected variable expression of a 2.5-kb JBP1 transcript in all tissues examined. Database analysis revealed JBP1 orthologs in mouse, nematode, fly, and yeast. Rho et al. (2001) found that fluorescence-tagged human PRMT5 localized predominantly to the cytoplasm of transfected COS-1 cells and human Chang liver cells. In his review, Wolf (2009) reported that 2 splice variants of PRMT5, which differ in their first exons, encode proteins of 637 and 620 amino acids.GENE FUNCTION
Gilbreth et al. (1998) demonstrated that S. pombe Skb1 and Shk1 are dosage-dependent mitotic inhibitors that interact with Cdc2 (116940), the cyclin-dependent kinase that initiates mitosis. When expressed in S. pombe, human SKB1 functionally substituted for the yeast protein, demonstrating that SKB1 protein function has been conserved. Using a protein pull-down assay, Pollack et al. (1999) confirmed that JBP1 interacted with mouse Jak2. The JBP1/Jak2 interaction did not require the Jak2 kinase domain. JBP1 also bound murine Jak1 (147795) and Jak3 (600173) and human TYK2 (176941) following expression in COS-1 cells. Crosslinking studies revealed that epitope-tagged JBP1 bound the universal methyl donor AdoMet in transfected COS cells. JBP1 specifically methylated histones H2A (see 602786) and H4 (see 602822) and myelin basic protein (MBP; 159430), but not cytochrome c (123970) or other histones, using AdoMet as the methyl donor. Lee et al. (2000) found that the yeast ortholog of JBP1, Hsl7, functioned as a protein methyltransferase. Human JBP1 complemented yeast lacking the Hsl7 gene. Rho et al. (2001) found that endogenous PRMT5 formed di ... More on the omim web site
April 10, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 26, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 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 604045 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed