Protein arginine methyltransferase 5

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

Protein arginine N-methyltransferase 5 is an enzyme that in humans is encoded by the PRMT5 gene. PRMT5 symmetrically dimethylates H2AR3, H4R3, H3R2, and H3R8 in vivo, all of which are linked to a range of transcriptional regulatory events (Cell. Mol. Life Sci. (2015) 72:2041–2059 DOI 10.1007/s00018-015-1847-9)

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.

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
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Brain histopathology	Normal
Salmonella infection	Normal
Citrobacter infection	Normal
All tests and analysis from

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

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

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

Interactions

Protein arginine methyltransferase 5 has been shown to interact with:

• CLNS1A,
• Janus kinase 2,
• SNRPD3,
• SUPT5H, and
• WD repeat-containing protein 77.

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.