PRMT1

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]
End	49,689,029 bp[1]
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)[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
	3276
	15469
	ENSG00000126457
	ENSMUSG00000109324
	Q99873
	Q9JIF0
	NM_001207042; NM_001536; NM_198318; NM_198319
	NM_001252476; NM_001252477; NM_019830
	NP_001193971; NP_001527; NP_938074
	NP_001239405; NP_001239406; NP_062804
	Wikidata
View/Edit Human	View/Edit Mouse

Protein arginine N-methyltransferase 1 is an enzyme that in humans is encoded by the PRMT1 gene.[5] The HRMT1L2 gene encodes a protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4.[6]

Function

PRMT1 gene encodes for the protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4 in eukaryotic cells.[6] Specifically altering histone H4 in eukaryotes gives it the ability to remodel chromatin acting as a post-translational modifier.[7]

Through regulation of gene expression, arginine methyltransferases control the cell cycle and death of eukaryotic cells.[7]

Reaction pathway

While all PRMT enzymes catalyze the methylation of arginine residues in proteins, PRMT1 is unique in that is catalyzes the formation of asymmetrically dimethylated arginine as opposed to the PRMT2 that catalyzes the formation of symmetrically dimethylated arginine.[8] Individual PRMT utilize S-adenosyl-L-methionine (SAM) as the methyl donor and catalyze methyl group transfer to the ω-nitrogen of an arginine residue.[8]

Clinical significance

In humans, these enzymes regulate gene expression and hence are involved in pathogenesis of many human diseases.[9] Using enzyme inhibitors for arginine methyltransferase 1, studies were able to demonstrate the enzyme's potential as an early catalyst of various cancers.[9][8][10]

Interactions

PRMT1 has been shown to interact with:

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[21]
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[22][23]

Model organisms have been used to study PRMT1 function and structure.

A conditional knockout mouse line, called Prmt1^{tm1a(EUCOMM)Wtsi}[24][25] 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.[26][27][28]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[22][29] Twenty three tests were carried out on mutant mice and three significant abnormalities were observed.[22] 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.[22]

References

GRCh38: Ensembl release 89: ENSG00000126457 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000109324 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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.
"Entrez Gene: PRMT1 protein arginine methyltransferase 1".
Qian K, Zhen G (2016-01-01). "Chapter 8 - Current Development of Protein Arginine Methyltransferase Inhibitors". In Medina-Franco JL (ed.). Epi-Informatics. Boston: Academic Press. pp. 231–256. doi:10.1016/b978-0-12-802808-7.00008-3. ISBN 978-0-12-802808-7.
Obianyo O, Osborne TC, Thompson PR (September 2008). "Kinetic mechanism of protein arginine methyltransferase 1". Biochemistry. 47 (39): 10420–7. doi:10.1021/bi800904m. PMC 2933744. PMID 18771293.
Zeng H, Xu W (2015-01-01). "Chapter 16 - Enzymatic Assays of Histone Methyltransferase Enzymes". In Zheng YG (ed.). Epigenetic Technological Applications. Boston: Academic Press. pp. 333–361. doi:10.1016/b978-0-12-801080-8.00016-8. ISBN 978-0-12-801080-8.
Carbone F, Montecucco F, Xu S, Banach M, Jamialahmadi T, Sahebkar A (August 2020). "Epigenetics in atherosclerosis: key features and therapeutic implications". Expert Opinion on Therapeutic Targets. 24 (8): 719–721. doi:10.1080/14728222.2020.1764535. PMID 32354276.
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.
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. S2CID 15016952.
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.
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.
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.
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. S2CID 8235923.
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.
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.
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.
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.
"Clinical chemistry data for Prmt1". Wellcome Trust Sanger Institute.
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. S2CID 85911512.
Mouse Resources Portal, Wellcome Trust Sanger Institute.
"International Knockout Mouse Consortium".
"Mouse Genome Informatics".
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.
Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
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. S2CID 18872015.
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.

External links

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000126457 - Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid9545638-5] 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.

[entrez-6] "Entrez Gene: PRMT1 protein arginine methyltransferase 1".

[Qian_2016-7] Qian K, Zhen G (2016-01-01). "Chapter 8 - Current Development of Protein Arginine Methyltransferase Inhibitors". In Medina-Franco JL (ed.). Epi-Informatics. Boston: Academic Press. pp. 231–256. doi:10.1016/b978-0-12-802808-7.00008-3. ISBN 978-0-12-802808-7.

[Obianyo_2008-8] Obianyo O, Osborne TC, Thompson PR (September 2008). "Kinetic mechanism of protein arginine methyltransferase 1". Biochemistry. 47 (39): 10420–7. doi:10.1021/bi800904m. PMC 2933744. PMID 18771293.

[Zeng_2015-9] Zeng H, Xu W (2015-01-01). "Chapter 16 - Enzymatic Assays of Histone Methyltransferase Enzymes". In Zheng YG (ed.). Epigenetic Technological Applications. Boston: Academic Press. pp. 333–361. doi:10.1016/b978-0-12-801080-8.00016-8. ISBN 978-0-12-801080-8.

[10] Carbone F, Montecucco F, Xu S, Banach M, Jamialahmadi T, Sahebkar A (August 2020). "Epigenetics in atherosclerosis: key features and therapeutic implications". Expert Opinion on Therapeutic Targets. 24 (8): 719–721. doi:10.1080/14728222.2020.1764535. PMID 32354276.

[pmid8663146-11] 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.

[pmid11856371-12] 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. S2CID 15016952.

[pmid15084609-13] 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.

[pmid11850402-14] 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.

[pmid12183049-15] 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.

[pmid16169070-16] 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. S2CID 8235923.

[pmid12529443-17] 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.

[pmid9029147-18] 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.

[pmid10749851-19] 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.

[pmid12718890-20] 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.

[Clinical_chemistry-21] "Clinical chemistry data for Prmt1". Wellcome Trust Sanger Institute.

[mgp_reference-22] 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. S2CID 85911512.

[23] Mouse Resources Portal, Wellcome Trust Sanger Institute.

[allele_ref-24] "International Knockout Mouse Consortium".

[mgi_allele_ref-25] "Mouse Genome Informatics".

[pmid21677750-26] 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.

[mouse_library-27] Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-28] 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. S2CID 18872015.

[pmid21722353-29] 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.