Q9JIF0 · ANM1_MOUSE
- ProteinProtein arginine N-methyltransferase 1
- GenePrmt1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids371 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in proteins such as ESR1, histone H2, H3 and H4, FMR1, ILF3, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15, EWS, HABP4, SERBP1, RBM15, FOXO1, CHTOP, MAP3K5/ASK1, MICU1 and NPRL2 (PubMed:15327772, PubMed:19858291, PubMed:38006878).
Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation (By similarity).
May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estrogen receptor (ER)-mediated transactivation, play a key role in neurite outgrowth and act as a negative regulator of megakaryocytic differentiation, by modulating p38 MAPK pathway (By similarity).
Methylates RBM15, promoting ubiquitination and degradation of RBM15 (By similarity).
Methylates MRE11 and TP53BP1, promoting the DNA damage response (By similarity).
Methylates FOXO1 and retains it in the nucleus increasing its transcriptional activity. Methylates CHTOP and this methylation is critical for its 5-hydroxymethylcytosine (5hmC)-binding activity (PubMed:19858291).
Methylates MAP3K5/ASK1 at 'Arg-85' and 'Arg-87' which promotes association of MAP3K5 with thioredoxin and negatively regulates MAP3K5 association with TRAF2, inhibiting MAP3K5 stimulation and MAP3K5-induced activation of JNK (By similarity).
Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (By similarity).
Plays a role in regulating alternative splicing in the heart (PubMed:30321814).
Methylates NPRL2 at 'Arg-78' leading to inhibition of its GTPase activator activity and then the GATOR1 complex and consequently inducing timely mTORC1 activation under methionine-sufficient conditions (PubMed:38006878).
Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation (By similarity).
May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estrogen receptor (ER)-mediated transactivation, play a key role in neurite outgrowth and act as a negative regulator of megakaryocytic differentiation, by modulating p38 MAPK pathway (By similarity).
Methylates RBM15, promoting ubiquitination and degradation of RBM15 (By similarity).
Methylates MRE11 and TP53BP1, promoting the DNA damage response (By similarity).
Methylates FOXO1 and retains it in the nucleus increasing its transcriptional activity. Methylates CHTOP and this methylation is critical for its 5-hydroxymethylcytosine (5hmC)-binding activity (PubMed:19858291).
Methylates MAP3K5/ASK1 at 'Arg-85' and 'Arg-87' which promotes association of MAP3K5 with thioredoxin and negatively regulates MAP3K5 association with TRAF2, inhibiting MAP3K5 stimulation and MAP3K5-induced activation of JNK (By similarity).
Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (By similarity).
Plays a role in regulating alternative splicing in the heart (PubMed:30321814).
Methylates NPRL2 at 'Arg-78' leading to inhibition of its GTPase activator activity and then the GATOR1 complex and consequently inducing timely mTORC1 activation under methionine-sufficient conditions (PubMed:38006878).
Catalytic activity
- L-arginyl-[protein] + 2 S-adenosyl-L-methionine = 2 H+ + N(omega),N(omega)-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-homocysteineThis reaction proceeds in the forward direction.
- L-arginyl-[protein] + S-adenosyl-L-methionine = H+ + N(omega)-methyl-L-arginyl-[protein] + S-adenosyl-L-homocysteineThis reaction proceeds in the forward direction.
- N(omega)-methyl-L-arginyl-[protein] + S-adenosyl-L-methionine = H+ + N(omega),N(omega)-dimethyl-L-arginyl-[protein] + S-adenosyl-L-homocysteineThis reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
10 μM | S-adenosyl-L-methionine |
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 63 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 72 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 96 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 118 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 147 | S-adenosyl-L-methionine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Active site | 162 | |||||
Sequence: E | ||||||
Active site | 171 | |||||
Sequence: E |
GO annotations
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameProtein arginine N-methyltransferase 1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ9JIF0
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Conditional knockout in cardiomyocytes results in dilated cardiomyopathy in juveniles and death within 60 days of birth with aberrant splicing occurring in a number of genes including Ktn1, Lmo7, Mef2a, Tmed2, Snap23, Sorbs1 and Ttn.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 98 | Inhibits methionine-stimulated mTORC1signaling pathway. | ||||
Sequence: G → R | ||||||
Mutagenesis | 145 | Increased stability of the protein caused by impaired ubiquitination by the SCF(FBXL17) complex. | ||||
Sequence: K → R | ||||||
Mutagenesis | 162 | Inhibits methionine-stimulated mTORC1 signaling pathway. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 212 | Increased stability of the protein. | ||||
Sequence: K → R | ||||||
Mutagenesis | 227 | Slightly reduced degradation, probably caused by reduced ubiquitination by the SCF(FBXL17) complex. | ||||
Sequence: I → D | ||||||
Mutagenesis | 228 | Mimicks residue acetylation; impaired interaction with FBXL17, leading to decreased ubiquitination by the SCF(FBXL17) complex. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 228 | Increased interaction with FBXL17, leading to increased ubiquitination by the SCF(FBXL17) complex. | ||||
Sequence: K → R | ||||||
Mutagenesis | 232 | Slightly reduced degradation, probably caused by reduced ubiquitination by the SCF(FBXL17) complex. | ||||
Sequence: I → D | ||||||
Mutagenesis | 233 | Mimicks residue acetylation; increased interaction with FBXL17, leading to increased ubiquitination by the SCF(FBXL17) complex. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 233 | Impaired interaction with FBXL17, leading to decreased ubiquitination by the SCF(FBXL17) complex. | ||||
Sequence: K → R | ||||||
Mutagenesis | 356 | Increased stability of the protein. | ||||
Sequence: K → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 12 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000212322 | 1-371 | Protein arginine N-methyltransferase 1 | |||
Sequence: MAAAEAANCIMENFVATLANGMSLQPPLEEVSCGQAESSEKPNAEDMTSKDYYFDSYAHFGIHEEMLKDEVRTLTYRNSMFHNRHLFKDKVVLDVGSGTGILCMFAAKAGARKVIGIECSSISDYAVKIVKANKLDHVVTIIKGKVEEVELPVEKVDIIISEWMGYCLFYESMLNTVLHARDKWLAPDGLIFPDRATLYVTAIEDRQYKDYKIHWWENVYGFDMSCIKDVAIKEPLVDVVDPKQLVTNACLIKEVDIYTVKVEDLTFTSPFCLQVKRNDYVHALVAYFNIEFTRCHKRTGFSTSPESPYTHWKQTVFYMEDYLTVKTGEEIFGTIGMRPNAKNNRDLDFTIDLDFKGQLCELSCSTDYRMR | ||||||
Modified residue | 134 | N6-succinyllysine | ||||
Sequence: K | ||||||
Cross-link | 145 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | ||||
Sequence: K | ||||||
Modified residue | 228 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 233 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 304 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 307 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Polyubiquitinated at Lys-145 by the SCF(FBXL17) complex, leading to its subsequent degradation (PubMed:28883095).
Ubiquitination is regulated by acetylation at Lys-228 and Lys-233 (PubMed:28883095).
Polyubiquitinated by E3 ubiquitin-protein ligase TRIM48, leading to suppression of MAP3K5/ASK1 methylation and subsequent MAP3K5 activation (By similarity).
Ubiquitination is regulated by acetylation at Lys-228 and Lys-233 (PubMed:28883095).
Polyubiquitinated by E3 ubiquitin-protein ligase TRIM48, leading to suppression of MAP3K5/ASK1 methylation and subsequent MAP3K5 activation (By similarity).
Acetylation at Lys-228 and Lys-233 regulates ubiquitination by the SCF(FBXL17) complex. Acetylated at Lys-233 by p300/EP300. Deacetylated at Lys-228 and Lys-233 by SIRT1.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the heart where it is detected in both cardiomyocytes and non-myocytes (at protein level).
Gene expression databases
Interaction
Subunit
Homodimer and heterodimer with PRMT8. Homooctamer; individual homodimers associates to form a homooctamer. Individual homodimers can associate to form a homohexamer. Interacts with BTG1, BTG2 and IFNAR1. Interacts with ILF3 and SUPT5H. Interacts with and methylates FOXO1, leading to the nuclear retention of FOXO1 and the stimulation of FOXO1 transcriptional activity. Methylation of FOXO1 is increased upon oxidative stress (By similarity).
Interacts with NFATC2IP. Interacts with and methylates CHTOP, thereby enabling the interaction of CHTOP with the 5FMC complex. Interacts with and probably methylates ATXN2L (By similarity).
Component of the methylosome, a 20S complex containing at least CLNS1A/pICln, PRMT5/SKB1, WDR77/MEP50, PRMT1 and ERH (By similarity).
Interacts with DHX9 (via RGG region) (By similarity).
Interacts (via N-terminus) with HABP4 (By similarity).
Interacts with MAP3K5/ASK1; the interaction results in MAP3K5 methylation by PRMT1 which inhibits MAP3K5 activation (By similarity).
Interacts with TRIM48; the interaction results in ubiquitination of PRMT1 by TRIM48, leading to PRMT1 proteasomal degradation and activation of MAP3K5 (By similarity).
Interacts with GATOR1 complex; this interaction is S-adenosyl-L-methionine (SAM) dependent and is perturbated by BMT2/SAMTOR in a SAM-sensitive manner (PubMed:38006878).
Interacts with GFI1; promoting recognition and binding of MRE11 and TP53BP1 substrates by PRMT1 (By similarity).
Interacts with NFATC2IP. Interacts with and methylates CHTOP, thereby enabling the interaction of CHTOP with the 5FMC complex. Interacts with and probably methylates ATXN2L (By similarity).
Component of the methylosome, a 20S complex containing at least CLNS1A/pICln, PRMT5/SKB1, WDR77/MEP50, PRMT1 and ERH (By similarity).
Interacts with DHX9 (via RGG region) (By similarity).
Interacts (via N-terminus) with HABP4 (By similarity).
Interacts with MAP3K5/ASK1; the interaction results in MAP3K5 methylation by PRMT1 which inhibits MAP3K5 activation (By similarity).
Interacts with TRIM48; the interaction results in ubiquitination of PRMT1 by TRIM48, leading to PRMT1 proteasomal degradation and activation of MAP3K5 (By similarity).
Interacts with GATOR1 complex; this interaction is S-adenosyl-L-methionine (SAM) dependent and is perturbated by BMT2/SAMTOR in a SAM-sensitive manner (PubMed:38006878).
Interacts with GFI1; promoting recognition and binding of MRE11 and TP53BP1 substrates by PRMT1 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9JIF0 | Axin1 Q14DJ8 | 3 | EBI-519055, EBI-4312125 | |
BINARY | Q9JIF0 | Chtop Q9CY57 | 8 | EBI-519055, EBI-6393116 | |
BINARY | Q9JIF0 | Khdrbs1 Q60749 | 2 | EBI-519055, EBI-519077 | |
BINARY | Q9JIF0 | Smad6 O35182 | 3 | EBI-519055, EBI-4321242 | |
BINARY | Q9JIF0-1 | Axin1 Q14DJ8 | 2 | EBI-4312217, EBI-4312125 | |
BINARY | Q9JIF0-3 | Axin1 Q14DJ8 | 2 | EBI-4422829, EBI-4312125 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 50-371 | SAM-dependent MTase PRMT-type | ||||
Sequence: KDYYFDSYAHFGIHEEMLKDEVRTLTYRNSMFHNRHLFKDKVVLDVGSGTGILCMFAAKAGARKVIGIECSSISDYAVKIVKANKLDHVVTIIKGKVEEVELPVEKVDIIISEWMGYCLFYESMLNTVLHARDKWLAPDGLIFPDRATLYVTAIEDRQYKDYKIHWWENVYGFDMSCIKDVAIKEPLVDVVDPKQLVTNACLIKEVDIYTVKVEDLTFTSPFCLQVKRNDYVHALVAYFNIEFTRCHKRTGFSTSPESPYTHWKQTVFYMEDYLTVKTGEEIFGTIGMRPNAKNNRDLDFTIDLDFKGQLCELSCSTDYRMR |
Sequence similarities
Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q9JIF0-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length371
- Mass (Da)42,436
- Last updated2000-10-01 v1
- ChecksumAEFCF63001B1A38C
Q9JIF0-2
- Name2
- Differences from canonical
- 13-30: Missing
Q9JIF0-3
- Name3
- Differences from canonical
- 1-29: MAAAEAANCIMENFVATLANGMSLQPPLE → M
Computationally mapped potential isoform sequences
There are 9 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A171KXD3 | A0A171KXD3_MOUSE | Prmt1 | 318 | ||
A0A140LJF4 | A0A140LJF4_MOUSE | Prmt1 | 193 | ||
A0A140LJG1 | A0A140LJG1_MOUSE | Prmt1 | 55 | ||
A0A140LJ68 | A0A140LJ68_MOUSE | Prmt1 | 122 | ||
A0A140LJ70 | A0A140LJ70_MOUSE | Prmt1 | 254 | ||
A0A140LIF7 | A0A140LIF7_MOUSE | Prmt1 | 113 | ||
A0A140LI33 | A0A140LI33_MOUSE | Prmt1 | 164 | ||
A0A140LHS4 | A0A140LHS4_MOUSE | Prmt1 | 217 | ||
A0A140LHF7 | A0A140LHF7_MOUSE | Prmt1 | 208 |
Features
Showing features for alternative sequence.
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF232716 EMBL· GenBank· DDBJ | AAF37292.1 EMBL· GenBank· DDBJ | mRNA | ||
AF232717 EMBL· GenBank· DDBJ | AAF37293.1 EMBL· GenBank· DDBJ | mRNA | ||
BC002249 EMBL· GenBank· DDBJ | AAH02249.1 EMBL· GenBank· DDBJ | mRNA |