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Identification
HMDB Protein ID HMDBP13357
Secondary Accession Numbers None
Name Protein arginine N-methyltransferase 5
Synonyms
  1. Prmt5
  2. Histone-arginine N-methyltransferase PRMT5
  3. Jak-binding protein 1
  4. Shk1 kinase-binding protein 1 homolog
  5. SKB1 homolog
Gene Name PRMT5
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function 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:15485929, PubMed:19584108, PubMed:19858291, PubMed:21917714, PubMed:23133559, PubMed:28263986). 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. Methylates SUPT5H and may regulate its transcriptional elongation properties. 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 (By similarity). Methylates histone H2A and H4 'Arg-3' during germ cell development (PubMed:16699504). Methylates histone H3 'Arg-8', which may repress transcription (PubMed:15485929). 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:19584108). Methylates RPS10 (By similarity). Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation. Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714). Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9. Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (By similarity). Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (PubMed:23133559). Methylates GM130/GOLGA2, regulating Golgi ribbon formation. Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (By similarity). Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (By similarity). Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression (By similarity). Symmetrically methylates NCL (By similarity). Methylates TP53; methylation might possibly affect TP53 target gene specificity (By similarity). Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through the catalysis of the symmetrical arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-associated protein) and the interaction with tudor domain-containing protein TDRD6 (PubMed:28263986).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
peptidyl-arginine methylation
histone arginine methylation
DNA-templated transcription, termination
Golgi ribbon formation
negative regulation of cell differentiation
peptidyl-arginine N-methylation
positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway
protein methylation
regulation of ERK1 and ERK2 cascade
endothelial cell activation
histone H4-R3 methylation
negative regulation of transcription from RNA polymerase II promoter
spliceosomal snRNP assembly
positive regulation of oligodendrocyte differentiation
regulation of transcription, DNA-dependent
circadian regulation of gene expression
regulation of DNA methylation
Cellular Component
cytosol
methylosome
protein-containing complex
cytoplasm
Golgi apparatus
nucleus
nucleoplasm
histone methyltransferase complex
Molecular Function
protein-arginine N-methyltransferase activity
protein-containing complex binding
methyl-CpG binding
histone methyltransferase activity (H4-R3 specific)
histone-arginine N-methyltransferase activity
chromatin binding
protein-arginine omega-N symmetric methyltransferase activity
ribonucleoprotein complex binding
p53 binding
E-box binding
transcription corepressor activity
identical protein binding
methyltransferase activity
protein heterodimerization activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 618
Molecular Weight 72679.22
Theoretical pI 6.495
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q8CIG8
UniProtKB/Swiss-Prot Entry Name ANM5_MOUSE
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  2. Pollack BP, Kotenko SV, He W, Izotova LS, Barnoski BL, Pestka S: The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity. J Biol Chem. 1999 Oct 29;274(44):31531-42. [PubMed:10531356 ]
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  4. Pal S, Vishwanath SN, Erdjument-Bromage H, Tempst P, Sif S: Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes. Mol Cell Biol. 2004 Nov;24(21):9630-45. [PubMed:15485929 ]
  5. Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001. [PubMed:21183079 ]
  6. Ancelin K, Lange UC, Hajkova P, Schneider R, Bannister AJ, Kouzarides T, Surani MA: Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nat Cell Biol. 2006 Jun;8(6):623-30. doi: 10.1038/ncb1413. Epub 2006 May 14. [PubMed:16699504 ]
  7. Vagin VV, Wohlschlegel J, Qu J, Jonsson Z, Huang X, Chuma S, Girard A, Sachidanandam R, Hannon GJ, Aravin AA: Proteomic analysis of murine Piwi proteins reveals a role for arginine methylation in specifying interaction with Tudor family members. Genes Dev. 2009 Aug 1;23(15):1749-62. doi: 10.1101/gad.1814809. Epub 2009 Jul 7. [PubMed:19584108 ]
  8. van Dijk TB, Gillemans N, Stein C, Fanis P, Demmers J, van de Corput M, Essers J, Grosveld F, Bauer UM, Philipsen S: Friend of Prmt1, a novel chromatin target of protein arginine methyltransferases. Mol Cell Biol. 2010 Jan;30(1):260-72. doi: 10.1128/MCB.00645-09. [PubMed:19858291 ]
  9. Fanis P, Gillemans N, Aghajanirefah A, Pourfarzad F, Demmers J, Esteghamat F, Vadlamudi RK, Grosveld F, Philipsen S, van Dijk TB: Five friends of methylated chromatin target of protein-arginine-methyltransferase[prmt]-1 (chtop), a complex linking arginine methylation to desumoylation. Mol Cell Proteomics. 2012 Nov;11(11):1263-73. doi: 10.1074/mcp.M112.017194. Epub 2012 Aug 7. [PubMed:22872859 ]
  10. Paul C, Sardet C, Fabbrizio E: The histone- and PRMT5-associated protein COPR5 is required for myogenic differentiation. Cell Death Differ. 2012 May;19(5):900-8. doi: 10.1038/cdd.2011.193. Epub 2011 Dec 23. [PubMed:22193545 ]
  11. Na J, Lee K, Kim HG, Shin JY, Na W, Jeong H, Lee JW, Cho S, Kim WS, Ju BG: Role of type II protein arginine methyltransferase 5 in the regulation of Circadian Per1 gene. PLoS One. 2012;7(10):e48152. doi: 10.1371/journal.pone.0048152. Epub 2012 Oct 25. [PubMed:23133559 ]
  12. Akpinar M, Lesche M, Fanourgakis G, Fu J, Anastassiadis K, Dahl A, Jessberger R: TDRD6 mediates early steps of spliceosome maturation in primary spermatocytes. PLoS Genet. 2017 Mar 6;13(3):e1006660. doi: 10.1371/journal.pgen.1006660. eCollection 2017 Mar. [PubMed:28263986 ]