PRMT5

| Available structures

PDB| Ortholog search: PDBe RCSB
| List of PDB id codes

4GQB, 4X60, 4X61, 4X63, 5EML, 5FA5, 5EMJ, 5EMK, 5EMM, 5C9Z

Identifiers
Aliases| PRMT5, HRMT1L5, IBP72, JBP1, SKB1, SKB1Hs, Protein arginine methyltransferase 5, HSL7
External IDs| OMIM: 604045 MGI: 1351645 HomoloGene: 4454 GeneCards: PRMT5
EC number| 2.1.1.321
| Gene location (Human)

Chr.| Chromosome 14 (human)[1]

Band| 14q11.2| Start| 22,920,525 bp[1]
End| 22,929,408 bp[1]
| Gene location (Mouse)

Chr.| Chromosome 14 (mouse)[2]

Band| 14|14 C2| Start| 54,507,187 bp[2]
End| 54,517,525 bp[2]
| RNA expression pattern

More reference expression data
| Gene ontology

Molecular function| • methyltransferase activity
• transferase activity
• histone methyltransferase activity (H4-R3 specific)
• GO:0001106 transcription corepressor activity
• methyl-CpG binding
• core promoter sequence-specific DNA binding
• GO:0001948 protein binding
• protein heterodimerization activity
• ribonucleoprotein complex binding
• histone-arginine N-methyltransferase activity
• protein-arginine N-methyltransferase activity
• protein-arginine omega-N symmetric methyltransferase activity
• identical protein binding
• GO:0032403 protein-containing complex binding
• E-box binding

Cellular component| • cytoplasm
• cytosol
• Golgi apparatus
• nucleoplasm
• methylosome
• nucleus
• histone methyltransferase complex
• protein-containing complex

Biological process| • regulation of mitotic nuclear division
• positive regulation of oligodendrocyte differentiation
• regulation of transcription, DNA-templated
• histone H4-R3 methylation
• rhythmic process
• DNA-templated transcription, termination
• negative regulation of cell differentiation
• peptidyl-arginine N-methylation
• endothelial cell activation
• circadian regulation of gene expression
• transcription, DNA-templated
• spliceosomal snRNP assembly
• liver regeneration
• methylation
• peptidyl-arginine methylation
• regulation of ERK1 and ERK2 cascade
• regulation of DNA methylation
• cell population proliferation
• Golgi ribbon formation
• protein methylation
• negative regulation of nucleic acid-templated transcription
• positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway
• regulation of signal transduction by p53 class mediator
• peptidyl-arginine methylation, to symmetrical-dimethyl arginine
• chromatin organization
• histone arginine methylation

Sources:Amigo / QuickGO
Orthologs
Species| Human| Mouse
Entrez| |

10419

27374

Ensembl| |

ENSG00000100462

ENSMUSG00000023110

UniProt| |

O14744

Q8CIG8

RefSeq (mRNA)| | NM_001039619
NM_001282953
NM_001282954
NM_001282955
NM_001282956

NM_006109

NM_013768
NM_001313906
NM_001313907

RefSeq (protein)| | NP_001034708
NP_001269882
NP_001269883
NP_001269884
NP_001269885

NP_006100

NP_001300835
NP_001300836
NP_038796

Location (UCSC)| Chr 14: 22.92 – 22.93 Mb| Chr 14: 54.51 – 54.52 Mb
PubMed search| [3]| [4]
Wikidata
| View/Edit Human| View/Edit Mouse

|

Protein arginine N-methyltransferase 5 is an enzyme that in humans is encoded by the PRMT5 gene.[5][6] PRMT5 symmetrically dimethylates H2AR3, H4R3, H3R2, and H3R8 in vivo, all of which are linked to a range of transcriptional regulatory events.[7]

PRMT5 is a highly conserved arginine methyltransferase that translocated from the cytoplasm to the nucleus at embryonic day ~E8.5, and during preimplantation development at the ~4-cell stage.[8]

## Contents

* 1 Model organisms
* 2 Interactions
* 3 References
* 4 Further reading

## Model organisms[edit]

Prmt5 knockout mouse phenotype  Characteristic | Phenotype

|

Homozygote viability | Abnormal
Recessive lethal study | Abnormal
Fertility | Normal
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 | Normal
Plasma immunoglobulins | Normal
Haematology | Normal[9]
Peripheral blood lymphocytes | Normal
Micronucleus test | Normal
Heart weight | Normal
Brain histopathology | Normal
Salmonella infection | Normal[10]
Citrobacter infection | Normal[11]
All tests and analysis from[12][13]

Model organisms have been used in the study of PRMT5 function. A conditional knockout mouse line, called Prmt5tm2a(EUCOMM)Wtsi[14][15] 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.[16][17][18]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[12] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice but no further abnormalities were observed.[12]

A conditional allele of Prmt5 in the mouse limb shows that it is essential for maintaining a progenitor population, as conditional mutants have limb defects [20]

## Interactions[edit]

Protein arginine methyltransferase 5 has been shown to interact with:

* CLNS1A,[21][22][23][24]
* Janus kinase 2,[25]
* SNRPD3,[23]
* SUPT5H,[26]
* WD repeat-containing protein 77,[21]
* RIOK1, [27][24]
* COPR5. [24][28]

PRMT5 has been shown to interact with CLNS1A, RIOK1 and COPR5 through an interface created by a shallow groove located on the TIM barrel domain of PRMT5 and the consensus sequence GQF[D/E]DA[E/D] located in the terminal regions of the adaptor proteins.[24][29]

## References[edit]

1. ^ a b c GRCh38: Ensembl release 89: ENSG00000100462 \- Ensembl, May 2017
2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023110 \- 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. ^ Gilbreth M, Yang P, Bartholomeusz G, Pimental RA, Kansra S, Gadiraju R, Marcus S (Jan 1999). "Negative regulation of mitosis in fission yeast by the shk1 interacting protein skb1 and its human homolog, Skb1Hs". Proc Natl Acad Sci U S A. 95 (25): 14781–6. doi:10.1073/pnas.95.25.14781. PMC 24526. PMID 9843966.
6. ^ "Entrez Gene: PRMT5 protein arginine methyltransferase 5".
7. ^ Stopa N, Krebs JE, Shechter D (June 2015). "The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond". Cellular and Molecular Life Sciences. 72 (11): 2041–59. doi:10.1007/s00018-015-1847-9. PMC 4430368. PMID 25662273.
8. ^ Kim S, Gunesdogan, U, Zylicz JJ, Hackett, JA, Cougot, D, Bao, S, Lee, C, Dietmann, S, Allen, GE, Sngupta, R, Surani MA (Nov 2014). "PRMT5 Protects Genomic Integrity during Global DNA Demethylation in Primordial Germ Cells and Preimplantation Embryos". Molecular Cell. 56 (4): 564–579. doi:10.1016/j.molcel.2014.10.003. PMC 4250265. PMID 25457166.
9. ^ "Haematology data for Prmt5". Wellcome Trust Sanger Institute.
10. ^ "Salmonella infection data for Prmt5". Wellcome Trust Sanger Institute.
11. ^ "Citrobacter infection data for Prmt5". Wellcome Trust Sanger Institute.
12. ^ a b c d 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.
13. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
14. ^ "International Knockout Mouse Consortium".
15. ^ "Mouse Genome Informatics".
16. ^ 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.
17. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
18. ^ 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.
19. ^ 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.
20. ^ Norrie JL, Li Q, Co S, Huang BL, Ding D, Uy JC, et al. (December 2016). "PRMT5 is essential for the maintenance of chondrogenic progenitor cells in the limb bud". Development. 143 (24): 4608–4619. doi:10.1242/dev.140715. PMC 5201029. PMID 27827819.
21. ^ a b Friesen WJ, Wyce A, Paushkin S, Abel L, Rappsilber J, Mann M, Dreyfuss G (Mar 2002). "A novel WD repeat protein component of the methylosome binds Sm proteins". J. Biol. Chem. 277 (10): 8243–7. doi:10.1074/jbc.M109984200. PMID 11756452.
22. ^ Krapivinsky G, Pu W, Wickman K, Krapivinsky L, Clapham DE (May 1998). "pICln binds to a mammalian homolog of a yeast protein involved in regulation of cell morphology". J. Biol. Chem. 273 (18): 10811–4. doi:10.1074/jbc.273.18.10811. PMID 9556550.
23. ^ a b Friesen WJ, Paushkin S, Wyce A, Massenet S, Pesiridis GS, Van Duyne G, Rappsilber J, Mann M, Dreyfuss G (Dec 2001). "The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins". Mol. Cell. Biol. 21 (24): 8289–300. doi:10.1128/MCB.21.24.8289-8300.2001. PMC 99994. PMID 11713266.
24. ^ a b c d Krzyzanowski A, Gasper R, Adihou H, 't Hart P, Waldmann H (Feb 2021). "Biochemical Investigation of the Interaction of pICln, RioK1 and COPR5 with the PRMT5‐MEP50 Complex". ChemBioChem. 22 (11): 1908–1914. doi:10.1002/cbic.202100079. PMC 8252068. PMID 33624332.
25. ^ Pollack BP, Kotenko SV, He W, Izotova LS, Barnoski BL, Pestka S (Oct 1999). "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity". J. Biol. Chem. 274 (44): 31531–42. doi:10.1074/jbc.274.44.31531. PMID 10531356.
26. ^ Kwak YT, Guo J, Prajapati S, Park KJ, Surabhi RM, Miller B, Gehrig P, Gaynor RB (Apr 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.
27. ^ Guderian G, Peter C, Wiesner J, Sickmann A, Schulze-Osthoff K, Fischer U, Grimmler M (Jan 2011). "RioK1, a new interactor of protein arginine methyltransferase 5 (PRMT5), competes with pICln for binding and modulates PRMT5 complex composition and substrate specificity". J Biol Chem. 286 (3): 1976–86. doi:10.1074/jbc.M110.148486. PMC 3023494. PMID 21081503.
28. ^ Lacroix M, Messaoudi SM, Rodier G, Cam AL, Sardet C, Fabbrizio E (May 2008). "The histone‐binding protein COPR5 is required for nuclear functions of the protein arginine methyltransferase PRMT5". EMBO. 9 (5): 452–8. doi:10.1038/embor.2008.45. PMC 2373370. PMID 18404153.
29. ^ Mulvaney KM, Blomquis C, Acharya N, Li R, O'Keefe M, Ranaghan M, Stokes M, Nelson AJ, Jain SS, Columbus J, Bozal FK, Skepner A, Raymond D, McKinney DC, Freyzon Y, Baidi Y, Porter D, Ianari A, McMillan B, Sellers WR (Aug 2020). "Molecular basis for substrate recruitment to the PRMT5 methylosome (preprint)". bioRxiv 10.1101/2020.08.22.256347.

## Further reading[edit]

* Krapivinsky G, Pu W, Wickman K, Krapivinsky L, Clapham DE (1998). "pICln binds to a mammalian homolog of a yeast protein involved in regulation of cell morphology". J. Biol. Chem. 273 (18): 10811–4. doi:10.1074/jbc.273.18.10811. PMID 9556550.
* Pollack BP, Kotenko SV, He W, Izotova LS, Barnoski BL, Pestka S (1999). "The human homologue of the yeast proteins Skb1 and Hsl7p interacts with Jak kinases and contains protein methyltransferase activity". J. Biol. Chem. 274 (44): 31531–42. doi:10.1074/jbc.274.44.31531. PMID 10531356.
* Schwärzler A, Kreienkamp HJ, Richter D (2000). "Interaction of the somatostatin receptor subtype 1 with the human homolog of the Shk1 kinase-binding protein from yeast". J. Biol. Chem. 275 (13): 9557–62. doi:10.1074/jbc.275.13.9557. PMID 10734105.
* 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.
* Friesen WJ, Paushkin S, Wyce A, Massenet S, Pesiridis GS, Van Duyne G, Rappsilber J, Mann M, Dreyfuss G (2001). "The methylosome, a 20S complex containing JBP1 and pICln, produces dimethylarginine-modified Sm proteins". Mol. Cell. Biol. 21 (24): 8289–300. doi:10.1128/MCB.21.24.8289-8300.2001. PMC 99994. PMID 11713266.
* Brahms H, Meheus L, de Brabandere V, Fischer U, Lührmann R (2001). "Symmetrical dimethylation of arginine residues in spliceosomal Sm protein B/B' and the Sm-like protein LSm4, and their interaction with the SMN protein". RNA. 7 (11): 1531–42. doi:10.1017/S135583820101442X. PMC 1370196. PMID 11720283.
* Meister G, Eggert C, Bühler D, Brahms H, Kambach C, Fischer U (2002). "Methylation of Sm proteins by a complex containing PRMT5 and the putative U snRNP assembly factor pICln". Curr. Biol. 11 (24): 1990–4. doi:10.1016/S0960-9822(01)00592-9. hdl:11858/00-001M-0000-0012-F501-7. PMID 11747828. S2CID 14742376.
* Friesen WJ, Wyce A, Paushkin S, Abel L, Rappsilber J, Mann M, Dreyfuss G (2002). "A novel WD repeat protein component of the methylosome binds Sm proteins". J. Biol. Chem. 277 (10): 8243–7. doi:10.1074/jbc.M109984200. PMID 11756452.
* Fabbrizio E, El Messaoudi S, Polanowska J, Paul C, Cook JR, Lee JH, Negre V, Rousset M, Pestka S, Le Cam A, Sardet C (2003). "Negative regulation of transcription by the type II arginine methyltransferase PRMT5". EMBO Rep. 3 (7): 641–5. doi:10.1093/embo-reports/kvf136. PMC 1084190. PMID 12101096.
* Jiang LQ, Wen SJ, Wang HY, Chen LY (2003). "Screening the proteins that interact with calpain in a human heart cDNA library using a yeast two-hybrid system". Hypertens. Res. 25 (4): 647–52. doi:10.1291/hypres.25.647. PMID 12358155.
* Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (2004). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801. S2CID 23783563.
* Kwak YT, Guo J, Prajapati S, Park KJ, Surabhi RM, Miller B, Gehrig P, Gaynor RB (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.
* Pal S, Yun R, Datta A, Lacomis L, Erdjument-Bromage H, Kumar J, Tempst P, Sif S (2003). "mSin3A/histone deacetylase 2- and PRMT5-containing Brg1 complex is involved in transcriptional repression of the Myc target gene cad". Mol. Cell. Biol. 23 (21): 7475–87. doi:10.1128/MCB.23.21.7475-7487.2003. PMC 207647. PMID 14559996.
* Yanagida M, Hayano T, Yamauchi Y, Shinkawa T, Natsume T, Isobe T, Takahashi N (2004). "Human fibrillarin forms a sub-complex with splicing factor 2-associated p32, protein arginine methyltransferases, and tubulins alpha 3 and beta 1 that is independent of its association with preribosomal ribonucleoprotein complexes". J. Biol. Chem. 279 (3): 1607–14. doi:10.1074/jbc.M305604200. PMID 14583623.
* Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, Metalnikov P, O'Donnell P, Taylor P, Taylor L, Zougman A, Woodgett JR, Langeberg LK, Scott JD, Pawson T (2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Curr. Biol. 14 (16): 1436–50. doi:10.1016/j.cub.2004.07.051. PMID 15324660. S2CID 2371325.
* Miranda TB, Khusial P, Cook JR, Lee JH, Gunderson SI, Pestka S, Zieve GW, Clarke S (2004). "Spliceosome Sm proteins D1, D3, and B/B' are asymmetrically dimethylated at arginine residues in the nucleus". Biochem. Biophys. Res. Commun. 323 (2): 382–7. doi:10.1016/j.bbrc.2004.08.107. PMID 15369763.
* Pal S, Vishwanath SN, Erdjument-Bromage H, Tempst P, Sif S (2004). "Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes". Mol. Cell. Biol. 24 (21): 9630–45. doi:10.1128/MCB.24.21.9630-9645.2004. PMC 522266. PMID 15485929.