PRMT1

Description

The PRMT1 (protein arginine methyltransferase 1) is a protein-coding gene located on chromosome 19.

Protein arginine N-methyltransferase 1 is an enzyme that in humans is encoded by the PRMT1 gene. The HRMT1L2 gene encodes a protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4.

== Function == PRMT1 gene encodes for the protein arginine methyltransferase that functions as a histone methyltransferase specific for histone H4 in eukaryotic cells. Specifically altering histone H4 in eukaryotes gives it the ability to remodel chromatin acting as a post-translational modifier. Through regulation of gene expression, arginine methyltransferases control the cell cycle and death of eukaryotic cells.

== Reaction pathway == While all PRMT enzymes catalyze the methylation of arginine residues in proteins, PRMT1 is unique in that is catalyzes the formation of asymmetric dimethylarginine as opposed to the PRMT2 that catalyzes the formation of symmetrically dimethylated arginine. Individual PRMT utilize S-adenosyl-L-methionine (SAM) as the methyl donor and catalyze methyl group transfer to the ω-nitrogen of an arginine residue.

== Clinical significance == In humans, these enzymes regulate gene expression and hence are involved in pathogenesis of many human diseases. Using enzyme inhibitors for arginine methyltransferase 1, studies were able to demonstrate the enzyme's potential as an early catalyst of various cancers.

PRMT1 is an arginine methyltransferase that adds one or two methyl groups to arginine residues in various proteins, including histone H2, H3, and H4. This enzyme primarily catalyzes the formation of asymmetric dimethylarginine (aDMA). Specifically, it is the main enzyme responsible for the monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively). This modification is a key marker for epigenetic transcriptional activation. PRMT1 plays a role in regulating the transcription of genes involved in estrogen receptor-mediated transactivation, neurite outgrowth, and megakaryocytic differentiation. It also affects the activity of several other proteins, including RBM15, FOXO1, CHTOP, MAP3K5/ASK1, and NPRL2, by methylation, which alters their function. For example, PRMT1 methylates RBM15, leading to its ubiquitination and degradation. Methylation of FOXO1 by PRMT1 increases its transcriptional activity and retains it in the nucleus. Methylation of CHTOP by PRMT1 is essential for its binding to 5-hydroxymethylcytosine (5hmC). PRMT1 can interact with several proteins, including BTG1, BTG2, NFATC2IP, IFNAR1, CHTOP, ILF3, SUPT5H, FOXO1, ATXN2L, CLNS1A/pICln, PRMT5/SKB1, WDR77/MEP50, ERH, DHX9, HABP4, MAP3K5/ASK1, TRIM48, and the GATOR1 complex. PRMT1 forms homodimers and homooctamers and can also form heterodimers with PRMT8. PRMT1 is a component of the methylosome, a complex involved in histone methylation.

PRMT1 is also known as ANM1, HCP1, HRMT1L2, IR1B4.

Associated Diseases

WES Whole Exome Sequencing