Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

PRMT5 (O14744) - Overview - Molecular Target Synopsis


PRMT5, Protein arginine N-methyltransferase 5
Enzyme Classification
UniProt O14744

Also Known as ANM5_HUMAN, PRMT5, HRMT1L5, IBP72, JBP1, SKB1

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). Methylates TP53; methylation might possibly affect TP53 target gene specificity (PubMed:19011621). Forms, at least, homodimers and homotetramers (PubMed:11152681). Component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A (PubMed:21081503). Found in a complex composed of PRMT5, WDR77 and RIOK1 (PubMed:21081503). RIOK1 and CLNS1A associate with PRMT5 in a mutually exclusive fashion, which allows the recruitment of distinct methylation substrates, such as nucleolin/NCL and Sm proteins, respectively (PubMed:21081503). Interacts with PRDM1 (By similarity). Identified in a complex composed of methylosome and PRMT1 and ERH (PubMed:25284789). Interacts with EGFR; methylates EGFR and stimulates EGFR-mediated ERK activation. Interacts with HOXA9. Interacts with SRGAP2. Found in a complex with COPRS, RUNX1 AND CBFB. Interacts with CHTOP; the interaction symmetrically methylates CHTOP, but seems to require the presence of PRMT1 (PubMed:25284789). Interacts with EPB41L3; this modulates methylation of target proteins. Component of a high molecular weight E2F-pocket protein complex, CERC (cyclin E1 repressor complex). Associates with SWI/SNF remodeling complexes containing SMARCA2 and SMARCA4. Interacts with JAK2, SSTR1, SUPT5H, BRAF and with active RAF1. Interacts with LSM11, PRMT7 and SNRPD3 (PubMed:17709427, PubMed:16087681). Interacts with COPRS; promoting its recruitment on histone H4. Interacts with CLNS1A/pICln (PubMed:21081503, PubMed:9556550). Identified in a complex with CLNS1A/pICln and Sm proteins. Interacts with RPS10 (PubMed:20159986). Interacts with WDR77. Interacts with IWS1. Interacts with CRY1. Interacts with POLR2A (PubMed:26700805). Interacts with SMN1/SMN2 (PubMed:26700805). Interacts with LYAR; this interaction is direct (PubMed:25092918). Interacts with STRAP (PubMed:19011621). Interacts with TP53 in response to DNA damage; the interaction is STRAP dependent (PubMed:19011621).

Inspect Structure
See all 3D Structures for PRMT5

Isoforms / Transcripts (Protein Coding)

Sub-cellular localization

UniProt: PRMT5 is active in the following subcellular-locations: cytoplasm, golgi apparatus, nucleus.
GO terms: PRMT5 is active in the following subcellular-locations: cytoplasm, cytosol, Golgi apparatus, histone methyltransferase complex, methylosome, nucleoplasm, nucleus.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project PRMT5 has gain in 3 cell-lines, loss in 1 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: K_562, NCI_ADR_RES, PC_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: CAL-12T, Hs 746T, NCI-H1581

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, HSMM, HeLa-S3

(see details)

3D Structures

For PRMT5 there are:
12 structures (12 chains) solved
12 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

PRMT5 has been screened with 669 compounds (1016 bioactivities), 354 compounds have bioactivities that show binding affinity of <= 500nM (563 bioactivities). (see details)