2.1.1.- Protein arginine N-methyltransferases | Enzymes | IUPHAR/BPS Guide to MALARIA PHARMACOLOGY

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2.1.1.- Protein arginine N-methyltransferases

2.1.1.- Protein arginine N-methyltransferases C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Protein arginine N-methyltransferases (PRMT, EC 2.1.1.-) encompass histone arginine N-methyltransferases (PRMT4, PRMT7, EC 2.1.1.125) and myelin basic protein N-methyltransferases (PRMT7, EC 2.1.1.126). They are dimeric or tetrameric enzymes which use S-adenosyl methionine as a methyl donor, generating S-adenosylhomocysteine as a by-product. They generate both mono-methylated and di-methylated products; these may be symmetric (SDMA) or asymmetric (N^G,N^G-dimethyl-L-arginine) versions, where both guanidine nitrogens are monomethylated or one of the two is dimethylated, respectively.

Enzymes

PRMT1 (protein arginine methyltransferase 1 ) Show summary »« Hide summary More detailed page go icon to follow link

PRMT2 (protein arginine methyltransferase 2 ) Show summary »« Hide summary

PRMT3 (protein arginine methyltransferase 3) Show summary »« Hide summary More detailed page go icon to follow link

PRMT4 (coactivator associated arginine methyltransferase 1) Show summary »« Hide summary More detailed page go icon to follow link

PRMT5 (protein arginine methyltransferase 5 ) Show summary »« Hide summary More detailed page go icon to follow link

Target Id

1256

Nomenclature

protein arginine methyltransferase 5

Common abbreviation

PRMT5

Previous and unofficial names

Histone-arginine N-methyltransferase | Jak-binding protein 1 | Jbp1 | HRMT1L5

Genes

PRMT5 (Hs), Prmt5 (Mm), Prmt5 (Rn)

Ensembl ID

ENSG00000100462 (Hs), ENSMUSG00000023110 (Mm), ENSRNOG00000012046 (Rn)

UniProtKB AC

O14744 (Hs), Q8CIG8 (Mm)

Selective inhibitors

EPZ015666 pK_i 8.3

DS-437 pIC₅₀ 5.2 [16]

cmp5 [PMID: 25742700] [1]

Comment

PRMT5 is the only PRMT reported to catalyse symmetrical methylation of arginine residues on histone tails [2], and acts to promote transcriptional silencing of target genes. Aberrant regulation of methylation is reported in disease [18], making the proteins controlling this modification attractive drug discovery targets. For example, PRMT5 is overexpressed in several malignancies [1,4,10,13,20], including mantle cell lymphoma (MCL) [5,12]. PRMT5 inhibition is considered to be a promising strategy for novel lymphoma therapies.

PRMT6 (protein arginine methyltransferase 6) Show summary »« Hide summary More detailed page go icon to follow link

Target Id

1257

Nomenclature

protein arginine methyltransferase 6

Common abbreviation

PRMT6

Previous and unofficial names

HRMT1L6 | HMT1 hnRNP methyltransferase-like 6

Genes

PRMT6 (Hs), Prmt6 (Mm), Prmt6 (Rn)

Ensembl ID

ENSG00000198890 (Hs), ENSMUSG00000049300 (Mm), ENSRNOG00000017187 (Rn)

UniProtKB AC

Q96LA8 (Hs), Q6NZB1 (Mm)

Inhibitors

C21 pIC₅₀ 5.1 [11]

Comment

Catalyses monomethylation and asymmetric dimethylation of arginine residues in histone and/or nonhistone proteins. Required for normal biological processes, and aberrantly expressed in several types of cancer [21].

PRMT7 (protein arginine methyltransferase 7 ) Show summary »« Hide summary More detailed page go icon to follow link

PRMT8 (protein arginine methyltransferase 8) Show summary »« Hide summary

Target Id

1259

Nomenclature

protein arginine methyltransferase 8

Common abbreviation

PRMT8

Previous and unofficial names

Heterogeneous nuclear ribonucleoprotein methyltransferase-like protein 4 | HRMT1L3 | HRMT1L4

Genes

PRMT8 (Hs), Prmt8 (Mm), Prmt8 (Rn)

Ensembl ID

ENSG00000111218 (Hs), ENSMUSG00000030350 (Mm), ENSRNOG00000053804 (Rn)

UniProtKB AC

Q9NR22 (Hs), Q6PAK3 (Mm)

Inhibitors

MS049 pIC₅₀ 5.8 [14]

Sub/family-selective inhibitors

MS023 pK_i 8.9 [6]

PRMT9 (F-box protein 11) Show summary »« Hide summary

Target Id	1260
Nomenclature	F-box protein 11
Common abbreviation	PRMT9
Previous and unofficial names	F-box only protein 11 \| FBXO11 \| VIT-1 \| vitiligo-associated protein 1 \| Jf \| FBX11 \| GENA 104
Genes	FBXO11 (Hs), Fbxo11 (Mm), Fbxo11 (Rn)
Ensembl ID	ENSG00000138081 (Hs), ENSMUSG00000005371 (Mm), ENSRNOG00000016396 (Rn)
UniProtKB AC	Q86XK2 (Hs), Q7TPD1 (Mm), Q7TSL3 (Rn)

PRMT10 (protein arginine methyltransferase 9) Show summary »« Hide summary

PRMT11 (F-box protein 10) Show summary »« Hide summary

References

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1. Alinari L, Mahasenan KV, Yan F, Karkhanis V, Chung JH, Smith EM, Quinion C, Smith PL, Kim L, Patton JT et al.. (2015) Selective inhibition of protein arginine methyltransferase 5 blocks initiation and maintenance of B-cell transformation. Blood, 125 (16): 2530-43. [PMID:25742700]

2. Branscombe TL, Frankel A, Lee JH, Cook JR, Yang Z, Pestka S, Clarke S. (2001) PRMT5 (Janus kinase-binding protein 1) catalyzes the formation of symmetric dimethylarginine residues in proteins. J Biol Chem, 276 (35): 32971-6. [PMID:11413150]

3. Cheng D, Yadav N, King RW, Swanson MS, Weinstein EJ, Bedford MT. (2004) Small molecule regulators of protein arginine methyltransferases. J Biol Chem, 279 (23): 23892-9. [PMID:15056663]

4. Chung J, Karkhanis V, Tae S, Yan F, Smith P, Ayers LW, Agostinelli C, Pileri S, Denis GV, Baiocchi RA et al.. (2013) Protein arginine methyltransferase 5 (PRMT5) inhibition induces lymphoma cell death through reactivation of the retinoblastoma tumor suppressor pathway and polycomb repressor complex 2 (PRC2) silencing. J Biol Chem, 288 (49): 35534-47. [PMID:24189068]

5. Copeland RA. (2013) Molecular pathways: protein methyltransferases in cancer. Clin Cancer Res, 19 (23): 6344-50. [PMID:23958745]

6. Eram MS, Shen Y, Szewczyk MM, Wu H, Senisterra G, Li F, Butler KV, Kaniskan U, Speed BA, dela Sena C et al.. (2015) A Potent, Selective, and Cell-Active Inhibitor of Human Type I Protein Arginine Methyltransferases. ACS Chemical Biology, Just Accepted Manuscript.

7. Ferreira de Freitas R, Eram MS, Smil D, Szewczyk MM, Kennedy S, Brown PJ, Santhakumar V, Barsyte-Lovejoy D, Arrowsmith CH, Vedadi M et al.. (2016) Discovery of a Potent and Selective Coactivator Associated Arginine Methyltransferase 1 (CARM1) Inhibitor by Virtual Screening. J Med Chem, 59 (14): 6838-47. [PMID:27390919]

8. Huynh T, Chen Z, Pang S, Geng J, Bandiera T, Bindi S, Vianello P, Roletto F, Thieffine S, Galvani A et al.. (2009) Optimization of pyrazole inhibitors of Coactivator Associated Arginine Methyltransferase 1 (CARM1). Bioorg Med Chem Lett, 19 (11): 2924-7. [PMID:19419866]

9. Kaniskan HÜ, Szewczyk MM, Yu Z, Eram MS, Yang X, Schmidt K, Luo X, Dai M, He F, Zang I et al.. (2015) A potent, selective and cell-active allosteric inhibitor of protein arginine methyltransferase 3 (PRMT3). Angew Chem Int Ed Engl, 54 (17): 5166-70. [PMID:25728001]

10. Li Y, Chitnis N, Nakagawa H, Kita Y, Natsugoe S, Yang Y, Li Z, Wasik M, Klein-Szanto AJ, Rustgi AK et al.. (2015) PRMT5 Is Required for Lymphomagenesis Triggered by Multiple Oncogenic Drivers. Cancer Discov, 5 (3): 288-303. [PMID:25582697]

11. Obianyo O, Causey CP, Jones JE, Thompson PR. (2011) Activity-based protein profiling of protein arginine methyltransferase 1. ACS Chem Biol, 6 (10): 1127-35. [PMID:21838253]

12. Pal S, Baiocchi RA, Byrd JC, Grever MR, Jacob ST, Sif S. (2007) Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma. EMBO J, 26 (15): 3558-69. [PMID:17627275]

13. Park JH, Szemes M, Vieira GC, Melegh Z, Malik S, Heesom KJ, Von Wallwitz-Freitas L, Greenhough A, Brown KW, Zheng YG et al.. (2015) Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells. Mol Oncol, 9 (3): 617-27. [PMID:25475372]

14. Shen Y, Szewczyk MM, Eram MS, Smil D, Kaniskan HÜ, Ferreira de Freitas R, Senisterra G, Li F, Schapira M, Brown PJ et al.. (2016) Discovery of a Potent, Selective, and Cell-Active Dual Inhibitor of Protein Arginine Methyltransferase 4 and Protein Arginine Methyltransferase 6. J Med Chem, 59 (19): 9124-9139. [PMID:27584694]

15. Siarheyeva A, Senisterra G, Allali-Hassani A, Dong A, Dobrovetsky E, Wasney GA, Chau I, Marcellus R, Hajian T, Liu F et al.. (2012) An allosteric inhibitor of protein arginine methyltransferase 3. Structure, 20 (8): 1425-35. [PMID:22795084]

16. Smil D, Eram MS, Li F, Kennedy S, Szewczyk MM, Brown PJ, Barsyte-Lovejoy D, Arrowsmith CH, Vedadi M, Schapira M. (2015) Discovery of a Dual PRMT5-PRMT7 Inhibitor. ACS Med Chem Lett, 6 (4): 408-12. [PMID:25893041]

17. Spannhoff A, Machmur R, Heinke R, Trojer P, Bauer I, Brosch G, Schüle R, Hanefeld W, Sippl W, Jung M. (2007) A novel arginine methyltransferase inhibitor with cellular activity. Bioorg Med Chem Lett, 17 (15): 4150-3. [PMID:17570663]

18. Stopa N, Krebs JE, Shechter D. (2015) The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond. Cell Mol Life Sci, 72 (11): 2041-59. [PMID:25662273]

19. Wan H, Huynh T, Pang S, Geng J, Vaccaro W, Poss MA, Trainor GL, Lorenzi MV, Gottardis M, Jayaraman L et al.. (2009) Benzo[d]imidazole inhibitors of Coactivator Associated Arginine Methyltransferase 1 (CARM1)--Hit to Lead studies. Bioorg Med Chem Lett, 19 (17): 5063-6. [PMID:19632837]

20. Yang F, Wang J, Ren HY, Jin J, Wang AL, Sun LL, Diao KX, Wang EH, Mi XY. (2015) Proliferative role of TRAF4 in breast cancer by upregulating PRMT5 nuclear expression. Tumour Biol, 36 (8): 5901-11. [PMID:25704480]

21. Yang Y, Bedford MT. (2013) Protein arginine methyltransferases and cancer. Nat Rev Cancer, 13 (1): 37-50. [PMID:23235912]

How to cite this family page

Database page citation:

2.1.1.- Protein arginine N-methyltransferases. Accessed on 07/02/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=254.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.