Q8CIG8 · ANM5_MOUSE
- ProteinProtein arginine N-methyltransferase 5
- GenePrmt5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids637 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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:15485929, PubMed:19584108, PubMed:19858291, PubMed:21917714, PubMed:23133559, PubMed:28263986).
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. Methylates SUPT5H and may regulate its transcriptional elongation properties (By similarity).
May methylate the N-terminal region of MBD2 (By similarity).
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 (By similarity).
Methylates histone H2A and H4 'Arg-3' during germ cell development (PubMed:16699504).
Methylates histone H3 'Arg-8', which may repress transcription (PubMed:15485929).
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 (PubMed:19584108).
Methylates RPS10 (By similarity).
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. 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. Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (By similarity).
Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (PubMed:23133559).
Methylates GM130/GOLGA2, regulating Golgi ribbon formation. Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner. 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. Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression. Symmetrically methylates NCL. Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity (By similarity).
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 (PubMed:28263986).
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. Methylates SUPT5H and may regulate its transcriptional elongation properties (By similarity).
May methylate the N-terminal region of MBD2 (By similarity).
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 (By similarity).
Methylates histone H2A and H4 'Arg-3' during germ cell development (PubMed:16699504).
Methylates histone H3 'Arg-8', which may repress transcription (PubMed:15485929).
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 (PubMed:19584108).
Methylates RPS10 (By similarity).
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. 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. Methylates and regulates SRGAP2 which is involved in cell migration and differentiation (By similarity).
Acts as a transcriptional corepressor in CRY1-mediated repression of the core circadian component PER1 by regulating the H4R3 dimethylation at the PER1 promoter (PubMed:23133559).
Methylates GM130/GOLGA2, regulating Golgi ribbon formation. Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner. 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. Along with LYAR, binds the promoter of gamma-globin HBG1/HBG2 and represses its expression. Symmetrically methylates NCL. Methylates p53/TP53; methylation might possibly affect p53/TP53 target gene specificity (By similarity).
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 (PubMed:28263986).
Catalytic activity
- L-arginyl-[protein] + 2 S-adenosyl-L-methionine = 2 H+ + N(omega),N(omega)'-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-homocysteine
Activity regulation
Activity is increased by EGF, HGF, FGF1 or FGF2 treatments, and slightly decreased by NGF treatment.
Features
Showing features for binding site, site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 324 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 327 | L-arginine residue (UniProtKB | ChEBI) of a protein (UniProtKB | ChEBI); substrate | ||||
Sequence: F | ||||||
Site | 327 | Critical for specifying symmetric addition of methyl groups | ||||
Sequence: F | ||||||
Binding site | 333-334 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: KY | ||||||
Binding site | 392 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 419-420 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: DM | ||||||
Active site | 435 | Proton donor/acceptor | ||||
Sequence: E | ||||||
Binding site | 435 | L-arginine residue (UniProtKB | ChEBI) of a protein (UniProtKB | ChEBI); substrate | ||||
Sequence: E | ||||||
Active site | 444 | Proton donor/acceptor | ||||
Sequence: E | ||||||
Binding site | 444 | L-arginine residue (UniProtKB | ChEBI) of a protein (UniProtKB | ChEBI); substrate | ||||
Sequence: E |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein arginine N-methyltransferase 5
- EC number
- Short namesPrmt5
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8CIG8
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes to promoter regions of target genes on chromosomes (By similarity).
Localizes to methylated chromatin (By similarity).
Localizes to methylated chromatin (By similarity).
Keywords
- Cellular component
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylalanine | ||||
Sequence: A | ||||||
Chain | PRO_0000212344 | 2-637 | Protein arginine N-methyltransferase 5 | |||
Sequence: AAMAVGGAGGSRVSSGRDLNCVPEIADTLGAVAKQGFDFLCMPVFHPRFKREFIQEPAKNRPGPQTRSDLLLSGRDWNTLIVGKLSPWIHPDSKVEKIRRNSEAAMLQELNFGAYLGLPAFLLPLNQEDNTNLARVLTNHIHTGHHSSMFWMRVPLVAPEDLRDDVIANAPTTHTEEYSGEEKTWMWWHNFRTLCDYSKRIAVALEIGADLPSNHVIDRWLGEPIKAAILPTSIFLTNKKGFPVLSKVQQRLIFRLLKLEVQFIITGTNHHSEKEFCSYLQYLEYLSQNRPPPNAYELFAKGYEDYLQSPLQPLMDNLESQTYEVFEKDPIKYSQYQQAIYKCLLDRVPEEEKETNVQVLMVLGAGRGPLVNASLRAAKQAERRIRLYAVEKNPNAVVTLENWQFEEWGSQVTVVSSDMREWVAPEKADIIVSELLGSFADNELSPECLDGAQHFLKDDGVSIPGEYTSFLAPISSSKLYNEVRACREKDRDPEAQFEMPYVVRLHNFHQLSAPKPCFTFSHPNRDPMIDNNRYCTLEFPVEVNTVLHGFAGYFETVLYRDITLSIRPETHSPGMFSWFPIFFPIKQPITVHEGQNICVRFWRCSNSKKVWYEWAVTAPVCSSIHNPTGRSYTIGL |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Forms, at least, homodimers and homotetramers. Component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A. Found in a complex composed of PRMT5, WDR77 and RIOK1. 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 (By similarity).
Interacts with PRDM1 (PubMed:16699504).
Identified in a complex composed of methylosome and PRMT1 and ERH. Interacts with EGFR; methylates EGFR and stimulates EGFR-mediated ERK activation. Interacts with HOXA9. Interacts with SRGAP2 (By similarity).
Found in a complex with COPRS, RUNX1 and CBFB (PubMed:22193545).
Interacts with CHTOP; the interaction symmetrically methylates CHTOP, but seems to require the presence of PRMT1 (PubMed:19858291, PubMed:22872859).
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. Interacts with COPRS; promoting its recruitment on histone H4. Interacts with CLNS1A/pICln. Identified in a complex with CLNS1A/pICln and Sm proteins. Interacts with RPS10. Interacts with WDR77 (By similarity).
Interacts with IWS1. Interacts with CRY1 (PubMed:23133559).
Interacts with POLR2A. Interacts with SMN1/SMN2. Interacts with LYAR; this interaction is direct. Interacts with TTC5/STRAP; this interaction is DNA damage-dependent and promotes PRMT5 interaction with p53/TP53. Interacts with p53/TP53 in response to DNA damage; the interaction is TTC5/STRAP dependent. Interacts with FAM47E; the interaction is direct, promotes PRMT5 localization to chromatin, and does not disrupt its association with WDR77 or STUB1 (By similarity).
Interacts with TDRD6 (PubMed:28263986).
Interacts with STUB1 (By similarity).
Interacts with MBD2 (By similarity).
Does not interact with MBD3 (By similarity).
Interacts with PRDM1 (PubMed:16699504).
Identified in a complex composed of methylosome and PRMT1 and ERH. Interacts with EGFR; methylates EGFR and stimulates EGFR-mediated ERK activation. Interacts with HOXA9. Interacts with SRGAP2 (By similarity).
Found in a complex with COPRS, RUNX1 and CBFB (PubMed:22193545).
Interacts with CHTOP; the interaction symmetrically methylates CHTOP, but seems to require the presence of PRMT1 (PubMed:19858291, PubMed:22872859).
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. Interacts with COPRS; promoting its recruitment on histone H4. Interacts with CLNS1A/pICln. Identified in a complex with CLNS1A/pICln and Sm proteins. Interacts with RPS10. Interacts with WDR77 (By similarity).
Interacts with IWS1. Interacts with CRY1 (PubMed:23133559).
Interacts with POLR2A. Interacts with SMN1/SMN2. Interacts with LYAR; this interaction is direct. Interacts with TTC5/STRAP; this interaction is DNA damage-dependent and promotes PRMT5 interaction with p53/TP53. Interacts with p53/TP53 in response to DNA damage; the interaction is TTC5/STRAP dependent. Interacts with FAM47E; the interaction is direct, promotes PRMT5 localization to chromatin, and does not disrupt its association with WDR77 or STUB1 (By similarity).
Interacts with TDRD6 (PubMed:28263986).
Interacts with STUB1 (By similarity).
Interacts with MBD2 (By similarity).
Does not interact with MBD3 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8CIG8 | Ccnd1 P25322 | 5 | EBI-2527009, EBI-847243 | |
BINARY | Q8CIG8 | Chtop Q9CY57 | 4 | EBI-2527009, EBI-6393116 | |
BINARY | Q8CIG8 | Cry1 P97784 | 2 | EBI-2527009, EBI-1266607 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 13-292 | TIM barrel | ||||
Sequence: RVSSGRDLNCVPEIADTLGAVAKQGFDFLCMPVFHPRFKREFIQEPAKNRPGPQTRSDLLLSGRDWNTLIVGKLSPWIHPDSKVEKIRRNSEAAMLQELNFGAYLGLPAFLLPLNQEDNTNLARVLTNHIHTGHHSSMFWMRVPLVAPEDLRDDVIANAPTTHTEEYSGEEKTWMWWHNFRTLCDYSKRIAVALEIGADLPSNHVIDRWLGEPIKAAILPTSIFLTNKKGFPVLSKVQQRLIFRLLKLEVQFIITGTNHHSEKEFCSYLQYLEYLSQNRP | ||||||
Domain | 308-615 | SAM-dependent MTase PRMT-type | ||||
Sequence: LQSPLQPLMDNLESQTYEVFEKDPIKYSQYQQAIYKCLLDRVPEEEKETNVQVLMVLGAGRGPLVNASLRAAKQAERRIRLYAVEKNPNAVVTLENWQFEEWGSQVTVVSSDMREWVAPEKADIIVSELLGSFADNELSPECLDGAQHFLKDDGVSIPGEYTSFLAPISSSKLYNEVRACREKDRDPEAQFEMPYVVRLHNFHQLSAPKPCFTFSHPNRDPMIDNNRYCTLEFPVEVNTVLHGFAGYFETVLYRDITLSIRPETHSPGMFSWFPIFFPIKQPITVHEGQNICVRFWRCSNSKKVWYEW | ||||||
Region | 465-637 | Beta barrel | ||||
Sequence: PGEYTSFLAPISSSKLYNEVRACREKDRDPEAQFEMPYVVRLHNFHQLSAPKPCFTFSHPNRDPMIDNNRYCTLEFPVEVNTVLHGFAGYFETVLYRDITLSIRPETHSPGMFSWFPIFFPIKQPITVHEGQNICVRFWRCSNSKKVWYEWAVTAPVCSSIHNPTGRSYTIGL | ||||||
Region | 488-494 | Dimerization | ||||
Sequence: REKDRDP |
Sequence similarities
Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length637
- Mass (Da)72,680
- Last updated2007-01-23 v3
- ChecksumE8014CA172B30543
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2I3BRG2 | A0A2I3BRG2_MOUSE | Prmt5 | 37 | ||
A0A0R4J049 | A0A0R4J049_MOUSE | Prmt5 | 637 | ||
F6QQQ6 | F6QQQ6_MOUSE | Prmt5 | 203 | ||
S4R295 | S4R295_MOUSE | Prmt5 | 63 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 169 | in Ref. 1; BAE21155/BAE38057 | ||||
Sequence: A → E | ||||||
Sequence conflict | 376 | in Ref. 3; AAF04503 | ||||
Sequence: L → F |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK132414 EMBL· GenBank· DDBJ | BAE21155.1 EMBL· GenBank· DDBJ | mRNA | ||
AK165165 EMBL· GenBank· DDBJ | BAE38057.1 EMBL· GenBank· DDBJ | mRNA | ||
BC023905 EMBL· GenBank· DDBJ | AAH23905.1 EMBL· GenBank· DDBJ | mRNA | ||
AF167573 EMBL· GenBank· DDBJ | AAF04503.1 EMBL· GenBank· DDBJ | mRNA |