Protein arginine N-methyltransferase 1 is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

that in humans is encoded by the ''PRMT1''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. The HRMT1L2 gene encodes a protein

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...

methyltransferase Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Ross ...

that functions as a

histone methyltransferase Histone methyltransferases (HMT) are histone-modifying enzymes (e.g., histone-lysine N-methyltransferases and histone-arginine N-methyltransferases), that catalyze the transfer of one, two, or three methyl groups to lysine and arginine residues of ...

specific for

histone H4 Histone H4 is one of the five main histone proteins involved in the structure of chromatin in eukaryote, eukaryotic cells. Featuring a main globular domain and a long N-terminus, N-terminal tail, H4 is involved with the structure of the nucleos ...

Function

PRMT1 gene encodes for the protein

that functions as a

specific for

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.

Interactions

PRMT1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with: *

BTG1 Protein BTG1 is a protein that in humans is encoded by the ''BTG1'' gene. Function The BTG1 gene locus has been shown to be involved in a t(8;12)(q24;q22) chromosomal translocation in a case of B-cell chronic lymphocytic leukemia. It is a memb ...

, *

BTG2 Protein BTG2 also known as BTG family member 2 or NGF-inducible anti-proliferative protein PC3 or NGF-inducible protein TIS21, is a protein that in humans is encoded by the ''BTG2'' gene (B-cell translocation gene 2) and in other mammals by the ho ...

, *

DHX9 ATP-dependent RNA helicase A (RHA; also known as DHX9, LKP, and NDHI) is an enzyme that in humans is encoded by the ''DHX9'' gene. Function DEAD/DEAH box helicases are proteins, and are putative RNA helicases. They are implicated in a number o ...

, * FUS, *

HNRNPR Heterogeneous nuclear ribonucleoprotein R is a protein that in humans is encoded by the ''HNRNPR'' gene. Function This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are R ...

, *

HNRPK Heterogeneous nuclear ribonucleoprotein K (also protein K) is a protein that in humans is encoded by the ''HNRNPK'' gene. It is found in the cell nucleus that binds to pre-messenger RNA (mRNA) as a component of heterogeneous ribonucleoprotein par ...

, *

IFNAR1 Interferon-alpha/beta receptor alpha chain is a protein that in humans is encoded by the ''IFNAR1'' gene. Function The protein encoded by this gene is a type I membrane protein that forms one of the two chains of a receptor for type I interfer ...

, *

ILF3 Interleukin enhancer-binding factor 3 is a protein that in humans is encoded by the ''ILF3'' gene. Function Nuclear factor of activated T-cells (NFAT) is a transcription factor required for T-cell expression of interleukin 2. NFAT binds to a s ...

, *

KHDRBS1 KH domain-containing, RNA-binding, signal transduction-associated protein 1 is a protein that in humans is encoded by the ''KHDRBS1'' gene. This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associate ...

, and * SUPT5H.

Model organisms

Model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...

s have been used to study PRMT1 function and structure. A conditional

knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

line, called ''Prmt1^{tm1a(EUCOMM)Wtsi}'' was generated as part of the

International Knockout Mouse Consortium The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to crea ...

program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized

phenotypic screen In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

to determine the effects of deletion. Twenty three tests were carried out on

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

mice and three significant abnormalities were observed. No

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

embryos were identified during gestation, and thus none survived until

weaning Weaning is the process of gradually introducing an infant human or another mammal to what will be its adult diet while withdrawing the supply of its mother's milk. The process takes place only in mammals, as only mammals produce milk. The infan ...

. The remaining tests were carried out on

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

mutant adult mice and females displayed increased circulating

creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an import ...

levels.

References

External links

* {{PDB Gallery, geneid=3276 Genes mutated in mice