Protein arginine N-methyltransferase 1 (PRMT1)
The protein contains 371 amino acids for an estimated molecular weight of 42462 Da.
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, ILF3, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15, EWS, HABP4 and SERBP1 (PubMed:10749851, PubMed:16879614, PubMed:26876602). 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. 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. Methylates RBM15, promoting ubiquitination and degradation of RBM15 (PubMed:26575292). 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:25284789). Methylates H4R3 in genes involved in glioblastomagenesis in a CHTOP- and/or TET1-dependent manner (PubMed:25284789). (updated: Jan. 16, 2019)
Protein identification was indicated in the following studies:
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs1804486 | |
| dbSNP:rs11673683 |
Biological Process
Cell surface receptor signaling pathway
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
Histone H4-R3 methylation
Histone methylation
In utero embryonic development
Negative regulation of megakaryocyte differentiation
Neuron projection development
Peptidyl-arginine methylation
Positive regulation of cell population proliferation
Positive regulation of erythrocyte differentiation
Positive regulation of hemoglobin biosynthetic process
Positive regulation of p38MAPK cascade
Protein homooligomerization
Protein methylation
Regulation of megakaryocyte differentiation
Molecular Function
Enzyme binding
Histone methyltransferase activity
Histone methyltransferase activity (H4-R3 specific)
Identical protein binding
Methyl-CpG binding
Methyltransferase activity
Mitogen-activated protein kinase p38 binding
N-methyltransferase activity
Protein methyltransferase activity
Protein-arginine N-methyltransferase activity
Protein-arginine omega-N asymmetric methyltransferase activity
Protein-arginine omega-N monomethyltransferase activity
RNA binding
S-adenosyl-L-methionine binding
The reference OMIM entry for this protein is 602950
Protein arginine methyltransferase 1; prmt1
Heterogeneous nuclear ribonucleoprotein methyltransferase 1-like 2; hrmt1l2
Hmt1-like 2
Interferon receptor 1-bound protein 4; ir1b4
DESCRIPTION
PRMT1, which catalyzes the formation of monomethylarginine and asymmetric dimethylarginine, is involved in a variety of processes, including gene transcription, DNA repair, and signal transduction (review by Wolf, 2009).CLONING
Protein arginine methylation is catalyzed by arginine methyltransferases. The bulk of methylated arginine residues in eukaryotic cells are found in heterogeneous nuclear ribonucleoproteins (hnRNPs), RNA-binding proteins that play essential roles in the metabolism of nuclear pre-mRNA. Lin et al. (1996) identified a rat cDNA encoding PRMT1 (protein-arginine N-methyltransferase 1; EC 2.1.1.23). Recombinant PRMT1 methylated histones and hnRNPA1 (164017) in vitro. By using a yeast 2-hybrid screen to identify proteins that interact with the intracytoplasmic domain of the interferon-alpha/beta receptor-1 (IFNAR1; 107450), Abramovich et al. (1997) identified a human cDNA encoding a protein that was nearly identical to PRMT1. The deduced 361-amino acid protein was designated IR1B4 for 'interferon receptor-1-bound protein 4.' Epitope-tagged IR1B4 bound the IFNAR1 intracytoplasmic domain in vitro. Antibodies against IFNAR1 coimmunoprecipitated a methyltransferase activity from human cell extracts. An antisense oligonucleotide strongly reduced methyltransferase activity in human cells, and caused them to become more resistant to growth inhibition by interferon. Abramovich et al. (1997) concluded that protein methylation, like phosphorylation, may be an important signaling mechanism for certain cytokine receptors. Scott et al. (1998) identified HRMT1L2 transcripts with variable 5-prime ends that encode 3 protein variants with different N-terminal regions. Rat PRMT1 and HRMT1L2 variant 2 (v2) share 95% sequence identity, but diverge at their N termini. The amino acid sequences of HRMT1L2 and HRMT1L1 (601961) are 27% identical. Recombinant protein methylated human hnRNPA1 and a yeast hnRNP in vitro. The HRMT1L2 gene complemented mutations in the yeast hnRNP methyltransferase gene HMT1. Northern blot analysis revealed that HRMT1L2 is expressed as a predominant 1.4-kb mRNA in various adult and fetal tissues. Additional larger and smaller bands were observed in some tissues. Scorilas et al. (2000) identified 3 splice variants of PRMT1, encoding deduced polypeptides of 343 (variant 1), 361 (variant 2), and 347 (variant 3) amino acids with molecular masses of 39.6, 41.5, and 39.9 kD, respectively. The full-length protein (v3) contains an in-frame stop codon in the middle of exon 3, and a second downstream start codon that resumes transcription. Variant 2 is predicted to contain 3 hydrophobic stretches, one of which may be a signal peptide. PRMT1 shares 96%, 34% and 29% sequence identity with rat PRMT1, human PRMT3 (603190), and human PRMT2 (HRMT1L1), respectively. RT-PCR revealed ubiquitous expression of all 3 splice variants, with highest expression in cerebellum, mammary gland, prostate, brain, and thyroid. The predominant variant differed among tissues. By PCR analysis, Scorilas et al. (2000) found that variants 1 and 2 were frequently downregulated in breast cancers in comparison to normal breast tissue. In his review, Wolf (2009) noted that most isoforms of PRMT1 localize to the nucleus.GENE FUNCTION
The S. cerevisiae ire15 mutation has an inositol auxotrophic phenotype and a defect in the expression of the inositol 1-phosphate synthase (INO1) gene. Nikawa et al. (1996) identified ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 602950 was added.
Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Jan. 21, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).