PRMT1

Protein arginine N-methyltransferase 1 is an enzyme that in humans is encoded by the PRMT1 gene.[5]

PRMT1
Identifiers
Aliases	PRMT1, ANM1, HCP1, HRMT1L2, IR1B4, protein arginine methyltransferase 1
External IDs	OMIM: 602950 MGI: 107846 HomoloGene: 21477 GeneCards: PRMT1
EC number	2.1.1.321
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.33 Start 49,675,786 bp[1] End 49,689,029 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 B3|7 29.07 cM Start 44,975,989 bp[2] End 44,986,568 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • methyltransferase activity • histone methyltransferase activity • transferase activity • histone methyltransferase activity (H4-R3 specific) • methyl-CpG binding • mitogen-activated protein kinase p38 binding • GO:0001948 protein binding • identical protein binding • enzyme binding • N-methyltransferase activity • protein-arginine omega-N asymmetric methyltransferase activity • RNA binding • protein methyltransferase activity • protein-arginine N-methyltransferase activity • histone-arginine N-methyltransferase activity • protein-arginine omega-N monomethyltransferase activity • S-adenosyl-L-methionine binding Cellular component • cytoplasm • nucleoplasm • methylosome • cell nucleus • cytosol Biological process • positive regulation of p38MAPK cascade • positive regulation of hemoglobin biosynthetic process • histone H4-R3 methylation • positive regulation of erythrocyte differentiation • negative regulation of megakaryocyte differentiation • cell surface receptor signaling pathway • methylation • peptidyl-arginine methylation • histone methylation • neuron projection development • peptidyl-arginine N-methylation • peptidyl-arginine methylation, to asymmetrical-dimethyl arginine • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest • regulation of transcription, DNA-templated • protein methylation • positive regulation of cell proliferation • regulation of megakaryocyte differentiation • in utero embryonic development • histone arginine methylation • protein homooligomerization Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3276	15469
Ensembl	ENSG00000126457	ENSMUSG00000109324
UniProt	Q99873	Q9JIF0
RefSeq (mRNA)	NM_001207042 NM_001536 NM_198318 NM_198319	NM_001252476 NM_001252477 NM_019830
RefSeq (protein)	NP_001193971 NP_001527 NP_938074	NP_001239405 NP_001239406 NP_062804
Location (UCSC)	Chr 19: 49.68 – 49.69 Mb	Chr 7: 44.98 – 44.99 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The HRMT1L2 gene encodes a protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4.[6]

Model organisms

Prmt1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal[7]
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
All tests and analysis from[8][9]

Model organisms have been used in the study of PRMT1 function. A conditional knockout mouse line, called Prmt1^{tm1a(EUCOMM)Wtsi}[10][11] was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[12][13][14]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty three tests were carried out on mutant mice and three significant abnormalities were observed.[8] No homozygous mutant embryos were identified during gestation, and thus none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and females displayed increased circulating creatinine levels.[8]

Interactions

PRMT1 has been shown to interact with:

• BTG1,[16][17]
• BTG2,[16][17]
• DHX9,[18]
• FUS,[19][20][21]
• HNRNPR,[20][21]
• HNRPK,[20][22]
• IFNAR1,[23]
• ILF3,[19][24]
• KHDRBS1,[22] and
• SUPT5H.[25]

References

1. GRCh38: Ensembl release 89: ENSG00000126457 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000109324 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Scott HS, Antonarakis SE, Lalioti MD, Rossier C, Silver PA, Henry MF (June 1998). "Identification and characterization of two putative human arginine methyltransferases (HRMT1L1 and HRMT1L2)". Genomics. 48 (3): 330–40. doi:10.1006/geno.1997.5190. PMID 9545638.
6. "Entrez Gene: PRMT1 protein arginine methyltransferase 1".
7. "Clinical chemistry data for Prmt1". Wellcome Trust Sanger Institute.
8. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
9. Mouse Resources Portal, Wellcome Trust Sanger Institute.
10. "International Knockout Mouse Consortium".
11. "Mouse Genome Informatics".
12. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
13. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
14. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
15. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
16. Lin WJ, Gary JD, Yang MC, Clarke S, Herschman HR (June 1996). "The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase". J. Biol. Chem. 271 (25): 15034–44. doi:10.1074/jbc.271.25.15034. PMID 8663146.
17. Berthet C, Guéhenneux F, Revol V, Samarut C, Lukaszewicz A, Dehay C, Dumontet C, Magaud JP, Rouault JP (January 2002). "Interaction of PRMT1 with BTG/TOB proteins in cell signalling: molecular analysis and functional aspects". Genes Cells. 7 (1): 29–39. doi:10.1046/j.1356-9597.2001.00497.x. PMID 11856371.
18. Smith WA, Schurter BT, Wong-Staal F, David M (May 2004). "Arginine methylation of RNA helicase a determines its subcellular localization". J. Biol. Chem. 279 (22): 22795–8. doi:10.1074/jbc.C300512200. PMID 15084609.
19. Lee J, Bedford MT (March 2002). "PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays". EMBO Rep. 3 (3): 268–73. doi:10.1093/embo-reports/kvf052. PMC 1084016. PMID 11850402.
20. Wada K, Inoue K, Hagiwara M (August 2002). "Identification of methylated proteins by protein arginine N-methyltransferase 1, PRMT1, with a new expression cloning strategy". Biochim. Biophys. Acta. 1591 (1–3): 1–10. doi:10.1016/s0167-4889(02)00202-1. PMID 12183049.
21. Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. hdl:11858/00-001M-0000-0010-8592-0. PMID 16169070.
22. Côté J, Boisvert FM, Boulanger MC, Bedford MT, Richard S (January 2003). "Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1". Mol. Biol. Cell. 14 (1): 274–87. doi:10.1091/mbc.E02-08-0484. PMC 140244. PMID 12529443.
23. Abramovich C, Yakobson B, Chebath J, Revel M (January 1997). "A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor". EMBO J. 16 (2): 260–6. doi:10.1093/emboj/16.2.260. PMC 1169633. PMID 9029147.
24. Tang J, Kao PN, Herschman HR (June 2000). "Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3". J. Biol. Chem. 275 (26): 19866–76. doi:10.1074/jbc.M000023200. PMID 10749851.
25. Kwak YT, Guo J, Prajapati S, Park KJ, Surabhi RM, Miller B, Gehrig P, Gaynor RB (April 2003). "Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties". Mol. Cell. 11 (4): 1055–66. doi:10.1016/s1097-2765(03)00101-1. PMID 12718890.

Further reading

• Kim S, Park GH, Paik WK (1999). "Recent advances in protein methylation: enzymatic methylation of nucleic acid binding proteins". Amino Acids. 15 (4): 291–306. doi:10.1007/BF01320895. PMID 9891755.
• Baldwin GS, Carnegie PR (1971). "Specific enzymic methylation of an arginine in the experimental allergic encephalomyelitis protein from human myelin". Science. 171 (3971): 579–81. doi:10.1126/science.171.3971.579. PMID 4924231.
• Rajpurohit R, Lee SO, Park JO, Paik WK, Kim S (1994). "Enzymatic methylation of recombinant heterogeneous nuclear RNP protein A1. Dual substrate specificity for S-adenosylmethionine:histone-arginine N-methyltransferase". J. Biol. Chem. 269 (2): 1075–82. PMID 8288564.
• Lin WJ, Gary JD, Yang MC, Clarke S, Herschman HR (1996). "The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase". J. Biol. Chem. 271 (25): 15034–44. doi:10.1074/jbc.271.25.15034. PMID 8663146.
• Nikawa J, Nakano H, Ohi N (1996). "Structural and functional conservation of human and yeast HCP1 genes which can suppress the growth defect of the Saccharomyces cerevisiae ire15 mutant". Gene. 171 (1): 107–11. doi:10.1016/0378-1119(96)00073-X. PMID 8675017.
• Abramovich C, Yakobson B, Chebath J, Revel M (1997). "A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor". EMBO J. 16 (2): 260–6. doi:10.1093/emboj/16.2.260. PMC 1169633. PMID 9029147.
• Klein S, Carroll JA, Chen Y, Henry MF, Henry PA, Ortonowski IE, Pintucci G, Beavis RC, Burgess WH, Rifkin DB (2000). "Biochemical analysis of the arginine methylation of high molecular weight fibroblast growth factor-2". J. Biol. Chem. 275 (5): 3150–7. doi:10.1074/jbc.275.5.3150. PMID 10652299.
• Tang J, Kao PN, Herschman HR (2000). "Protein-arginine methyltransferase I, the predominant protein-arginine methyltransferase in cells, interacts with and is regulated by interleukin enhancer-binding factor 3". J. Biol. Chem. 275 (26): 19866–76. doi:10.1074/jbc.M000023200. PMID 10749851.
• Nichols RC, Wang XW, Tang J, Hamilton BJ, High FA, Herschman HR, Rigby WF (2000). "The RGG domain in hnRNP A2 affects subcellular localization". Exp. Cell Res. 256 (2): 522–32. doi:10.1006/excr.2000.4827. PMID 10772824.
• Zhang X, Zhou L, Cheng X (2000). "Crystal structure of the conserved core of protein arginine methyltransferase PRMT3". EMBO J. 19 (14): 3509–19. doi:10.1093/emboj/19.14.3509. PMC 313989. PMID 10899106.
• Koh SS, Chen D, Lee YH, Stallcup MR (2001). "Synergistic enhancement of nuclear receptor function by p160 coactivators and two coactivators with protein methyltransferase activities". J. Biol. Chem. 276 (2): 1089–98. doi:10.1074/jbc.M004228200. PMID 11050077.
• Scorilas A, Black MH, Talieri M, Diamandis EP (2001). "Genomic organization, physical mapping, and expression analysis of the human protein arginine methyltransferase 1 gene". Biochem. Biophys. Res. Commun. 278 (2): 349–59. doi:10.1006/bbrc.2000.3807. PMID 11097842.
• Rho J, Choi S, Seong YR, Cho WK, Kim SH, Im DS (2001). "Prmt5, which forms distinct homo-oligomers, is a member of the protein-arginine methyltransferase family". J. Biol. Chem. 276 (14): 11393–401. doi:10.1074/jbc.M008660200. PMID 11152681.
• Mowen KA, Tang J, Zhu W, Schurter BT, Shuai K, Herschman HR, David M (2001). "Arginine methylation of STAT1 modulates IFNalpha/beta-induced transcription". Cell. 104 (5): 731–41. doi:10.1016/S0092-8674(01)00269-0. PMID 11257227.
• Wang H, Huang ZQ, Xia L, Feng Q, Erdjument-Bromage H, Strahl BD, Briggs SD, Allis CD, Wong J, Tempst P, Zhang Y (2001). "Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor". Science. 293 (5531): 853–7. doi:10.1126/science.1060781. PMID 11387442.
• Strahl BD, Briggs SD, Brame CJ, Caldwell JA, Koh SS, Ma H, Cook RG, Shabanowitz J, Hunt DF, Stallcup MR, Allis CD (2001). "Methylation of histone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1". Curr. Biol. 11 (12): 996–1000. doi:10.1016/S0960-9822(01)00294-9. PMID 11448779.
• Rho J, Choi S, Seong YR, Choi J, Im DS (2001). "The Arginine-1493 Residue in QRRGRTGR1493G Motif IV of the Hepatitis C Virus NS3 Helicase Domain Is Essential for NS3 Protein Methylation by the Protein Arginine Methyltransferase 1". J. Virol. 75 (17): 8031–44. doi:10.1128/JVI.75.17.8031-8044.2001. PMC 115047. PMID 11483748.
• Lee J, Bedford MT (2002). "PABP1 identified as an arginine methyltransferase substrate using high-density protein arrays". EMBO Rep. 3 (3): 268–73. doi:10.1093/embo-reports/kvf052. PMC 1084016. PMID 11850402.

External links

• Overview of all the structural information available in the PDB for UniProt: Q99873 (Protein arginine N-methyltransferase 1) at the PDBe-KB.