Protein arginine methyltransferase 5

Protein arginine methyltransferase 5
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4GQB​, 4X60​, 4X61​, 4X63​
Identifiers
Symbols	PRMT5 ; HRMT1L5; IBP72; JBP1; SKB1; SKB1Hs
External IDs	OMIM: 604045 MGI: 1351645 HomoloGene: 4454 ChEMBL: 1795116 GeneCards: PRMT5 Gene
EC number	2.1.1.125
Gene ontology Molecular function • core promoter sequence-specific DNA binding • transcription corepressor activity • protein binding • methyltransferase activity • histone-arginine N-methyltransferase activity • protein complex binding • protein-arginine omega-N symmetric methyltransferase activity • ribonucleoprotein complex binding • protein heterodimerization activity Cellular component • nucleus • nucleoplasm • cytoplasm • cytosol • methylosome • histone methyltransferase complex Biological process • spliceosomal snRNP assembly • chromatin organization • transcription, DNA-templated • regulation of transcription, DNA-templated • regulation of mitotic nuclear division • cell proliferation • gene expression • peptidyl-arginine methylation • peptidyl-arginine methylation, to symmetrical-dimethyl arginine • circadian regulation of gene expression • ncRNA metabolic process • histone arginine methylation • peptidyl-arginine N-methylation • endothelial cell activation • histone H4-R3 methylation • regulation of DNA methylation • negative regulation of cell differentiation • positive regulation of oligodendrocyte differentiation • regulation of ERK1 and ERK2 cascade • liver regeneration • negative regulation of nucleic acid-templated transcription Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	10419	27374
Ensembl	ENSG00000100462	ENSMUSG00000023110
UniProt	O14744	Q8CIG8
RefSeq (mRNA)	NM_001039619	NM_013768
RefSeq (protein)	NP_001034708	NP_038796
Location (UCSC)	Chr 14: 22.92 – 22.93 Mb	Chr 14: 54.51 – 54.52 Mb
PubMed search

Protein arginine N-methyltransferase 5 is an enzyme that in humans is encoded by the PRMT5 gene.^[1][2]

Model organisms

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[3]
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Normal
Salmonella infection	Normal[4]
Citrobacter infection	Normal[5]
All tests and analysis from[6][7]

Model organisms have been used in the study of PRMT5 function. A conditional knockout mouse line, called Prmt5^{tm2a(EUCOMM)Wtsi[8][9]} 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.^[10][11][12]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[6][13] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.^[6] 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.^[6]

Interactions

Protein arginine methyltransferase 5 has been shown to interact with:

• CLNS1A,^[14][15][16]
• Janus kinase 2,^[17]
• SNRPD3,^[16]
• SUPT5H,^[18] and
• WD repeat-containing protein 77.^[14]

References

1. 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.
2. "Entrez Gene: PRMT5 protein arginine methyltransferase 5".
3. "Haematology data for Prmt5". Wellcome Trust Sanger Institute.
4. "Salmonella infection data for Prmt5". Wellcome Trust Sanger Institute.
5. "Citrobacter infection data for Prmt5". Wellcome Trust Sanger Institute.
6. 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.
7. Mouse Resources Portal, Wellcome Trust Sanger Institute.
8. "International Knockout Mouse Consortium".
9. "Mouse Genome Informatics".
10. 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.
11. Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.

Further reading

• 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. PMID 11747828.
• 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.
• 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.
• 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.