Protein arginine N-methyltransferase 5

CovInDB Protein

O14744

Name

Protein arginine N-methyltransferase 5

Encoding Gene

PRMT5

Synonyms

• 72 kDa ICln-binding protein
• Histone-arginine N-methyltransferase PRMT5
• Jak-binding protein 1
• Shk1 kinase-binding protein 1 homolog (SKB1 homolog; SKB1Hs)

Taxonomy

Homo sapiens (Human)

Description

  Show details

Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503, PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653, PubMed:21081503, PubMed:21258366, PubMed:21917714, PubMed:22269951).
Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles (PubMed:11747828, PubMed:12411503, PubMed:17709427).
Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890).
May methylate the N-terminal region of MBD2 (PubMed:16428440).
Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development (By similarity).
Methylates histone H3 'Arg-8', which may repress transcription (By similarity).
Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (By similarity).
Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation (PubMed:21258366, PubMed:21917714).
Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714).
Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9 (PubMed:22269951).
Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (PubMed:20810653).
Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (By similarity).
Methylates GM130/GOLGA2, regulating Golgi ribbon formation (PubMed:20421892).
Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789).
Symmetrically methylates POLR2A, a modification that allows the recruitment to POLR2A of proteins including SMN1/SMN2 and SETX. This is required for resolving RNA-DNA hybrids created by RNA polymerase II, that form R-loop in transcription terminal regions, an important step in proper transcription termination (PubMed:26700805).
Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression (PubMed:25092918).
Symmetrically methylates NCL (PubMed:21081503).
Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity (PubMed:19011621).
Involved in spliceosome maturation and mRNA splicing in prophase I spermatocytes through the catalysis of the symmetrical arginine dimethylation of SNRPB (small nuclear ribonucleoprotein-associated protein) and the interaction with tudor domain-containing protein TDRD6 (By similarity).

Sequence

  Show details

MAAMAVGGAGGSRVSSGRDLNCVPEIADTLGAVAKQGFDFLCMPVFHPRFKREFIQEPAKNRPGPQTRSDLLLSGRDWNTLIVGKLSPWIRPDSKVEKIRRNSEAAMLQELNFGAYLGLPAFLLPLNQEDNTNLARVLTNHIHTGHHSSMFWMRVPLVAPEDLRDDIIENAPTTHTEEYSGEEKTWMWWHNFRTLCDYSKRIAVALEIGADLPSNHVIDRWLGEPIKAAILPTSIFLTNKKGFPVLSKMHQRLIFRLLKLEVQFIITGTNHHSEKEFCSYLQYLEYLSQNRPPPNAYELFAKGYEDYLQSPLQPLMDNLESQTYEVFEKDPIKYSQYQQAIYKCLLDRVPEEEKDTNVQVLMVLGAGRGPLVNASLRAAKQADRRIKLYAVEKNPNAVVTLENWQFEEWGSQVTVVSSDMREWVAPEKADIIVSELLGSFADNELSPECLDGAQHFLKDDGVSIPGEYTSFLAPISSSKLYNEVRACREKDRDPEAQFEMPYVVRLHNFHQLSAPQPCFTFSHPNRDPMIDNNRYCTLEFPVEVNTVLHGFAGYFETVLYQDITLSIRPETHSPGMFSWFPILFPIKQPITVREGQTICVRFWRCSNSKKVWYEWAVTAPVCSAIHNPTGRSYTIGL

Active Site

Feature Key	Position(s)	Description
Binding site	324	S-adenosyl-L-methionine
Binding site	327	L-arginine residue
Site	327	Critical for specifying symmetric addition of methyl groups
Binding site	333-334	S-adenosyl-L-methionine
Binding site	392	S-adenosyl-L-methionine
Binding site	419-420	S-adenosyl-L-methionine
Active site	435	Proton donor/acceptor
Binding site	435	L-arginine residue
Active site	444	Proton donor/acceptor
Binding site	444	L-arginine residue

Structure

Check covalent ligand-protein complexes.

PDB:  6V0P

Show Surface

Site View

Reference

UniProt

  Download