• Molecules and Cells
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• v.38 no.8
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• pp.723-728
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• 2015

Smurf2, a member of the HECT domain E3 ligase family, is well known for its role as a negative regulator of TGF-${\beta}$ signaling by targeting Smads and TGF-${\beta}$ receptor. However, the regulatory mechanism of Smurf2 has not been elucidated. Arginine methylation is a type of post-translational modification that produces monomethylated or dimethylated arginine residues. In this report, we demonstrated methylation of Smurf2 by PRMT1. In vitro methylation assay showed that Smurf2, not Smurf1, was methylated by PRMT1. Among the type I PRMT family, only PRMT1 showed activity for Smurf2. Transiently expressed Smurf2 was methylated by PRMT1, indicating Smurf2 is a novel substrate of PRMT1. Using deletion constructs, methylation sites were shown to be located within amino acid region 224-298 of Smurf2. In vitro methylation assay following point mutation of putative methylation sites confirmed the presence of Arg232, Arg234, Arg237, and Arg239. Knockdown of PRMT1 resulted in increased Smurf2 expression as well as inhibition of TGF-${\beta}$-mediated reporter activity. Although it is unclear whether or not increased Smurf2 expression can be directly attributed to lack of methylation of arginine residues, our results suggest that methylation by PRMT1 may regulate Smurf2 stability and control TGF-${\beta}$ signaling.

• Journal of Life Science
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• v.8 no.1
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• pp.109-117
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• 1998

The synthesis and methylation in vivo of myleline basic protein(MBP) during the mouse brain devlopment was found to be the highest in youngest brain and declined progressively in mature brains. The relative rate of protein synthesis and methylation was a maximal ration in the youngest brain, This high ratio was wdll correlated with the higher protein methylase I (PM I) activity in younger brains. The jimpy mouse is the most severely affected dysmyelinating mutant and is characterized by failure to incorporate MBP into myelin. sheath. The MBP-specific PM I activity in 15-, 18-, and 21-days old hemizygous jimpy mice(jp/y)brains decreased by 20, 50 and 75%, respectively. Myelin fraction with different degrees of compaction were isolated from bovine brain, the most compact myelin fraction exhibited higher methylaccepting activity than the less compact dense fractions.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.330.1-330.1
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• 2002

Arginine methylation is a common post-translation protein modification in eukaryotic cells. Protein-arginine N-methyltransferase transfer methyl groups from S-adenosyl-L-methionine to the guanidino group of arginine residues. However. The significant of this modification has been questionable. because it occurs rarely and is present at very low abundance. Recently, the discovery of two protein arginine methyltransferase, PRMT1 and CARM1, as cofactors required for responses to muclear Hormone receptors provided an indicationthat arginine methylationhave an important role in transcriptional regulation. (omitted)

• Archives of Pharmacal Research
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• v.10 no.3
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• pp.193-196
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• 1987

Protein methylation occurs ubiquitously in nature and involves N-methylation of lysine, arginine, histidine, alanine, proline and glutamine, O-methylesterfication o dicarboxylic acids, and S-methylation of cysteine and methionine. In nature, methylated amino acids accur in highly specialized proteins such as histones, flagella proteins, myosin, actin, ribosomal proteins. hn RNA-bound protein, HMG-1 and HMG-2 protein, opsin, EF-Tu, EF-$1\alpha$, porcine heart citrate synthase, calmodulin, ferredoxin, $1\alpha$-amylase, heat shock protein, scleroderma antigen, nucleolar protein C23 and IF-3l.

• BMB Reports
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• v.57 no.7
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• pp.330-335
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• 2024

Arginine methylation, which is catalyzed by protein arginine methyltransferases (Prmts), is known to play a key role in various biological processes. However, the function of Prmts in osteogenic differentiation of mesenchymal stem cells (MSCs) has not been clearly understood. In the current study, we attempted to elucidate a positive role of Prmt7 in osteogenic differentiation. Prmt7-depleted C3H/10T1/2 cells or bone marrow mesenchymal stem cells (BMSCs) showed the attenuated expression of osteogenic specific genes and Alizarin red staining compared to the wild-type cells. Furthermore, we found that Prmt7 deficiency reduced the activation of bone morphogenetic protein (BMP) signaling cascade, which is essential for the regulation of cell fate commitment and osteogenesis. Taken together, our data indicate that Prmt7 plays important regulatory roles in osteogenic differentiation.

• YAKHAK HOEJI
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• v.31 no.5
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• pp.266-272
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• 1987

It is reasonably well known that there is a relationship between myelin formation and methylation of myelin basic protein in nerve cells. One of the suggestions is that arginine methylation of myelin basic protein could be of aid in the conjugation of myelin protein with the nonpolar lipid to form myelin. Abnormality in methylation of myclin basic protein might induce the neurological diseases in experimental animals as well as in human being. In the biological system, the methylation reaction is catalyzed by protein methaylse I using S-adenosyl-L-methionine as methyl donor. In this study, we examined the changes of S-adenosyl-L-methionine concentration and protein methylase I activity in developing rat brain tissues. The results are sumraerized as followings: (1) In brain tissues of fetus rat, the concentration of S-adenosyl-L-methionine was gradually decreased until to birth. However, the concentration in brain tissues of infant rat was suddenly increased at 7th day(just before myelination occur) birth. (2) Protein methylase I activity was decreased until to birth in brain of fetus rat and increased temporally just after birth, However, the enzyme activity showed no changes around 7th day after birth.

• Bulletin of the Korean Chemical Society
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• v.30 no.11
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• pp.2542-2548
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• 2009

Direct methylation behaviors of 20 amino acids with tetramethylammonium hydroxide (TMAH) were studied under diluted conditions with silica. Amino acid concentration was controlled by dilution with silica ($SiO_2$) and the molar ratios of amino acid/silica were 0.20, 0.50, and 2.0. The molar ratios of amino acid/TMAH (0.51 - 4.64) also varied. It was found that arginine, asparagine, aspartic acid, cysteine, glutamic acid, and glutamine did not generate any directly methylated pyrolysis products, whereas alanine, glycine, isoleucine, leucine, methionine, phenylanaline, valine, and proline generated all the directly methylated pyrolysis products. Tri- and tetra methylated products of lysine consisted of two types. Histidine and threonine hardly generated the partly methylated products. Mono- and dimethylated products of serine, tryptophan, and tyrosine were not observed. Relative intensities of the methylated products varied with the amino acid concentration, TMAH concentration, and pyrolysis temperature. Direct methylation behaviors of amino acids were explained by the structural characteristics of amino acids.

• BMB Reports
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• v.40 no.5
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• pp.617-624
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• 2007

Protein arginine methylation is a posttranslational modification involved in various cellular functions including cell signaling, protein subcellular localization and transcriptional regulation. We analyze the protein arginine methyltransferases (PRMTs) that catalyze the formation of methylarginines in porcine brain. We fractionated the brain extracts and determined the PRMT activities as well as the distribution of different PRMT proteins in subcellular fractions of porcine brain. The majority of the type I methyltransferase activities that catalyze the formation of asymmetric dimethylarginines was in the cytosolic S3 fraction. High specific activity of the methyltransferase was detected in the S4 fraction (high-salt stripping of the ultracentrifugation precipitant P3 fraction), indicating that part of the PRMT was peripherally associated with membrane and ribosomal fractions. The amount and distribution of PRMT1 are consistent with the catalytic activity. The elution patterns from gel filtration and anion exchange chromatography also indicate that the type I activity in S3 and S4 are mostly from PRMT1. Our results suggest that part of the type I arginine methyltransferases in brains, mainly PRMT1, are sequestered in an inactive form as they associated with membranes or large subcellular complexes. Our biochemical analyses confirmed the complex distribution of different PRMTs and implicate their regulation and catalytic activities in brain.

• Archives of Pharmacal Research
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• v.12 no.2
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• pp.79-87
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• 1989

Enzymatic methylation of arginine and lysine residues of several cytochrome c and lysine residue of calmodulin always resulted in lowering of their respective isoelectric points (pI). Employing cytochromes c derived from various sources, we examined a possible relationship between the degree of amino acid sequence degeneracy and the magnitude of change in the pI values by enzymatic methylation, and found that there was no correlation between these two parameters. By constructing space-filling models of oligopeptide fragments adjacent to the potential methylation sites, we have noted that not all the methylatable residues are able to form hydrogen bonds prior to the methylation. Two preparations of yeast apocytochrome c, one chemically prepared by removing heme from holocytochrome c and the other by translating yeast iso-1-cytochrome c mRNA in vitro, exhibited slightly higher Stokes radii than the homologous holocytochrome c, indicating relatively 'relaxed or open' conformation of the protein. However, when the in vitro synthesized methylated apocytochrome c was compared with the unmethylated counter-part, the Stokes radius of the latter was found to be larger.

• Korean Journal of Microbiology
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• v.48 no.2
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• pp.79-86
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• 2012

ErmSF is one of the Erm family proteins which catalyze S-adenosyl-$_L$-methionine dependent modification of a specific adenine residue (A2058, E. coli numbering) in bacterial 23S rRNA, thereby conferring resistance to clinically important macrolide, lincosamide and streptogramin B ($MLS_B$) antibiotics. $^{222}FXPXPXVXS^{230}$ (ErmSF numbering) sequence appears to be a consensus sequence among the Erm family. This sequence was supposed to be involved in direct interaction with the target adenine from the structural studies of Erm protein ErmC'. But in DNA methyltarnsferase M. Taq I, this interaction have been identified biochemically and from the complex structure with substrate. Arginine 223 and 227 in this sequence are not conserved among Erm proteins, but because of the basic nature of residues, it was expected to interact with RNA substrates. Two amino acid residues were replaced with Ala by site-directed mutagenesis. Two mutant proteins still maintained its activity in vivo and resistant to the antibiotic erythromycin. Compared to the wild-type ErmSF, R223A and R227A proteins retained about 50% and 88% of activity in vitro, respectively. Even though those arginine residues are not essential in the catalytic step, with their positive charge they may play an important role for RNA binding.