Tchem PRMT5 Protein arginine N-methyltransferase 5

Protein Summary

Description

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:21258366, PubMed:21917714, PubMed:22269951, PubMed:21081503). 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:12411503, PubMed:11747828, PubMed:17709427). Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890). 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. Methylates histone H3 'Arg-8', which may repress transcription. 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:21917714, PubMed:21258366). 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). This gene encodes an enzyme that belongs to the methyltransferase family. The encoded protein catalyzes the transfer of methyl groups to the amino acid arginine, in target proteins that include histones, transcriptional elongation factors and the tumor suppressor p53. This gene plays a role in several cellular processes, including transcriptional regulation, and the assembly of small nuclear ribonucleoproteins. A pseudogene of this gene has been defined on chromosome 4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

Uniprot Accession IDs

• O14744
• A8MTP3
• A8MZ91
• B4DX49
• B4DY30
• B5BU10
• D3DS33
• E2QRE7
• Q6IBR1
• Q9UKH1

Gene Name

• PRMT5

Ensembl ID

• ENST00000216350
• ENSP00000216350
• ENSG00000100462
• ENST00000324366
• ENSP00000319169
• ENST00000397440
• ENSP00000380582
• ENST00000397441
• ENSP00000380583
• ENST00000553897
• ENSP00000452555

Symbol

• HRMT1L5
• IBP72
• JBP1
• SKB1
• HSL7
• JBP1
• SKB1
• IBP72
• SKB1Hs
• HRMT1L5

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.97
kinase perturbation	0.93
hub protein	0.92
histone modification site profile	0.9
transcription factor binding site profile	0.82

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Protein Arginine N-methyltransferase 5

DTO Classes

Protein / Epigenetic Regulator / Writer / Protein Methyltransferase / Protein Arginine Methyltransferase / Protein Arginine N-methyltransferase 5

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 420.75   (req: < 5)

Gene RIFs: 230   (req: <= 3)

Antibodies: 574   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 420.75   (req: >= 5)

Gene RIFs: 230   (req: > 3)

Antibodies: 574   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 29

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 354

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0