MRM2_HUMAN
ID MRM2_HUMAN Reviewed; 246 AA.
AC Q9UI43; Q24JR8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=rRNA methyltransferase 2, mitochondrial {ECO:0000303|PubMed:24036117};
DE EC=2.1.1.- {ECO:0000305|PubMed:25074936};
DE AltName: Full=16S rRNA (uridine(1369)-2'-O)-methyltransferase {ECO:0000303|PubMed:25074936};
DE AltName: Full=16S rRNA [Um1369] 2'-O-methyltransferase {ECO:0000303|PubMed:25074936};
DE AltName: Full=Protein ftsJ homolog 2 {ECO:0000303|PubMed:11827451};
DE Flags: Precursor;
GN Name=MRM2 {ECO:0000303|PubMed:24036117};
GN Synonyms=FJH1 {ECO:0000303|Ref.1}, FTSJ2 {ECO:0000303|PubMed:11827451};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jin D.-Y., Jeang K.-T.;
RT "Chromosomal localization of human FJH1.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=11827451; DOI=10.1006/geno.2001.6670;
RA Ching Y.-P., Zhou H.-J., Yuan J.-G., Qiang B.-Q., Kung H., Jin D.-Y.;
RT "Identification and characterization of FTSJ2, a novel human nucleolar
RT protein homologous to bacterial ribosomal RNA methyltransferase.";
RL Genomics 79:2-6(2002).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=24036117; DOI=10.1074/jbc.m113.515692;
RA Lee K.W., Okot-Kotber C., LaComb J.F., Bogenhagen D.F.;
RT "Mitochondrial ribosomal RNA (rRNA) methyltransferase family members are
RT positioned to modify nascent rRNA in foci near the mitochondrial DNA
RT nucleoid.";
RL J. Biol. Chem. 288:31386-31399(2013).
RN [6]
RP FUNCTION.
RX PubMed=25074936; DOI=10.1074/jbc.c114.581868;
RA Lee K.W., Bogenhagen D.F.;
RT "Assignment of 2'-O-methyltransferases to modification sites on the
RT mammalian mitochondrial large subunit 16S rRNA.";
RL J. Biol. Chem. 289:24936-24942(2014).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25009282; DOI=10.1091/mbc.e14-01-0014;
RA Rorbach J., Boesch P., Gammage P.A., Nicholls T.J., Pearce S.F., Patel D.,
RA Hauser A., Perocchi F., Minczuk M.;
RT "MRM2 and MRM3 are involved in biogenesis of the large subunit of the
RT mitochondrial ribosome.";
RL Mol. Biol. Cell 25:2542-2555(2014).
RN [8]
RP VARIANT MTDPS17 ARG-189, AND INVOLVEMENT IN MTDPS17.
RX PubMed=28973171; DOI=10.1093/hmg/ddx314;
RA Garone C., D'Souza A.R., Dallabona C., Lodi T., Rebelo-Guiomar P.,
RA Rorbach J., Donati M.A., Procopio E., Montomoli M., Guerrini R.,
RA Zeviani M., Calvo S.E., Mootha V.K., DiMauro S., Ferrero I., Minczuk M.;
RT "Defective mitochondrial rRNA methyltransferase MRM2 causes MELAS-like
RT clinical syndrome.";
RL Hum. Mol. Genet. 26:4257-4266(2017).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) OF 51-246 IN COMPLEX WITH
RP S-ADENOSYL-L-METHIONINE.
RG Structural genomics consortium (SGC);
RT "The crystal structure of human ftsJ homolog 2 (E.coli) protein in complex
RT with AdoMet.";
RL Submitted (FEB-2009) to the PDB data bank.
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent 2'-O-ribose
CC methyltransferase that catalyzes the formation of 2'-O-methyluridine at
CC position 1369 (Um1369) in the 16S mitochondrial large subunit ribosomal
CC RNA (mtLSU rRNA), a universally conserved modification in the peptidyl
CC transferase domain of the mtLSU rRNA. {ECO:0000269|PubMed:25009282,
CC ECO:0000269|PubMed:25074936}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-adenosyl-L-methionine + uridine(1369) in 16S rRNA = 2'-O-
CC methyluridine(1369) in 16S rRNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:47764, Rhea:RHEA-COMP:11903, Rhea:RHEA-COMP:11904,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:65315, ChEBI:CHEBI:74478;
CC Evidence={ECO:0000305|PubMed:25074936};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:24036117,
CC ECO:0000269|PubMed:25009282}.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in
CC muscle, placenta, and heart. {ECO:0000269|PubMed:11827451}.
CC -!- DISEASE: Mitochondrial DNA depletion syndrome 17 (MTDPS17)
CC [MIM:618567]: An autosomal recessive mitochondrial disorder
CC characterized by childhood onset of rapidly progressive encephalopathy,
CC stroke-like episodes, lactic acidosis, hypocitrullinemia, multiple
CC defects of oxidative phosphorylation, mitochondrial complex I and IV
CC deficiency, and reduced mtDNA copy number.
CC {ECO:0000269|PubMed:28973171}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. RNA methyltransferase RlmE family. {ECO:0000305}.
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DR EMBL; AF093415; AAF22488.1; -; mRNA.
DR EMBL; BC114514; AAI14515.1; -; mRNA.
DR CCDS; CCDS5328.1; -.
DR RefSeq; NP_037525.1; NM_013393.1.
DR PDB; 2NYU; X-ray; 1.76 A; A/B=51-246.
DR PDB; 7O9K; EM; 3.10 A; n=1-246.
DR PDB; 7O9M; EM; 2.50 A; n=1-246.
DR PDB; 7ODS; EM; 3.10 A; z=1-246.
DR PDBsum; 2NYU; -.
DR PDBsum; 7O9K; -.
DR PDBsum; 7O9M; -.
DR PDBsum; 7ODS; -.
DR AlphaFoldDB; Q9UI43; -.
DR SMR; Q9UI43; -.
DR BioGRID; 118996; 90.
DR IntAct; Q9UI43; 10.
DR STRING; 9606.ENSP00000242257; -.
DR iPTMnet; Q9UI43; -.
DR PhosphoSitePlus; Q9UI43; -.
DR BioMuta; MRM2; -.
DR DMDM; 9910866; -.
DR EPD; Q9UI43; -.
DR jPOST; Q9UI43; -.
DR MassIVE; Q9UI43; -.
DR PaxDb; Q9UI43; -.
DR PeptideAtlas; Q9UI43; -.
DR PRIDE; Q9UI43; -.
DR ProteomicsDB; 84473; -.
DR Antibodypedia; 24314; 67 antibodies from 16 providers.
DR DNASU; 29960; -.
DR Ensembl; ENST00000242257.14; ENSP00000242257.8; ENSG00000122687.19.
DR Ensembl; ENST00000440306.3; ENSP00000392343.3; ENSG00000122687.19.
DR GeneID; 29960; -.
DR KEGG; hsa:29960; -.
DR MANE-Select; ENST00000242257.14; ENSP00000242257.8; NM_013393.3; NP_037525.1.
DR CTD; 29960; -.
DR DisGeNET; 29960; -.
DR GeneCards; MRM2; -.
DR HGNC; HGNC:16352; MRM2.
DR HPA; ENSG00000122687; Low tissue specificity.
DR MalaCards; MRM2; -.
DR MIM; 606906; gene.
DR MIM; 618567; phenotype.
DR neXtProt; NX_Q9UI43; -.
DR OpenTargets; ENSG00000122687; -.
DR PharmGKB; PA28418; -.
DR VEuPathDB; HostDB:ENSG00000122687; -.
DR eggNOG; KOG4589; Eukaryota.
DR GeneTree; ENSGT00730000111241; -.
DR HOGENOM; CLU_009422_4_2_1; -.
DR InParanoid; Q9UI43; -.
DR OMA; HRQTDHL; -.
DR OrthoDB; 1039414at2759; -.
DR PhylomeDB; Q9UI43; -.
DR TreeFam; TF316701; -.
DR BRENDA; 2.1.1.166; 2681.
DR BRENDA; 2.1.1.B123; 2681.
DR PathwayCommons; Q9UI43; -.
DR Reactome; R-HSA-6793080; rRNA modification in the mitochondrion.
DR SignaLink; Q9UI43; -.
DR BioGRID-ORCS; 29960; 191 hits in 1086 CRISPR screens.
DR ChiTaRS; MRM2; human.
DR EvolutionaryTrace; Q9UI43; -.
DR GenomeRNAi; 29960; -.
DR Pharos; Q9UI43; Tbio.
DR PRO; PR:Q9UI43; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9UI43; protein.
DR Bgee; ENSG00000122687; Expressed in gastrocnemius and 102 other tissues.
DR ExpressionAtlas; Q9UI43; baseline and differential.
DR Genevisible; Q9UI43; HS.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; ISS:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0008173; F:RNA methyltransferase activity; IBA:GO_Central.
DR GO; GO:0008650; F:rRNA (uridine-2'-O-)-methyltransferase activity; IMP:FlyBase.
DR GO; GO:1902775; P:mitochondrial large ribosomal subunit assembly; IMP:FlyBase.
DR GO; GO:0001510; P:RNA methylation; IBA:GO_Central.
DR GO; GO:0000451; P:rRNA 2'-O-methylation; TAS:Reactome.
DR GO; GO:0031167; P:rRNA methylation; NAS:BHF-UCL.
DR GO; GO:0006364; P:rRNA processing; NAS:BHF-UCL.
DR Gene3D; 3.40.50.150; -; 1.
DR HAMAP; MF_01547; RNA_methyltr_E; 1.
DR InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR InterPro; IPR015507; rRNA-MeTfrase_E.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF01728; FtsJ; 1.
DR PIRSF; PIRSF005461; 23S_rRNA_mtase; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Methyltransferase; Mitochondrion;
KW Primary mitochondrial disease; Reference proteome; rRNA processing;
KW S-adenosyl-L-methionine; Transferase; Transit peptide.
FT TRANSIT 1..18
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 19..246
FT /note="rRNA methyltransferase 2, mitochondrial"
FT /id="PRO_0000155576"
FT ACT_SITE 194
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P0C0R7"
FT BINDING 83..86
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.9"
FT BINDING 112
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.9"
FT BINDING 129..130
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.9"
FT BINDING 154
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|Ref.9"
FT VARIANT 189
FT /note="G -> R (in MTDPS17)"
FT /evidence="ECO:0000269|PubMed:28973171"
FT /id="VAR_083280"
FT CONFLICT 73
FT /note="G -> S (in Ref. 2; AAI14515)"
FT /evidence="ECO:0000305"
FT HELIX 56..67
FT /evidence="ECO:0007829|PDB:2NYU"
FT STRAND 75..79
FT /evidence="ECO:0007829|PDB:2NYU"
FT HELIX 85..93
FT /evidence="ECO:0007829|PDB:2NYU"
FT TURN 94..97
FT /evidence="ECO:0007829|PDB:2NYU"
FT STRAND 107..111
FT /evidence="ECO:0007829|PDB:2NYU"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:2NYU"
FT HELIX 133..142
FT /evidence="ECO:0007829|PDB:2NYU"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:2NYU"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:2NYU"
FT HELIX 163..184
FT /evidence="ECO:0007829|PDB:2NYU"
FT STRAND 185..195
FT /evidence="ECO:0007829|PDB:2NYU"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:2NYU"
FT HELIX 202..211
FT /evidence="ECO:0007829|PDB:2NYU"
FT STRAND 212..218
FT /evidence="ECO:0007829|PDB:2NYU"
FT STRAND 230..237
FT /evidence="ECO:0007829|PDB:2NYU"
SQ SEQUENCE 246 AA; 27424 MW; DB7B9978695409D1 CRC64;
MAGYLKLVCV SFQRQGFHTV GSRCKNRTGA EHLWLTRHLR DPFVKAAKVE SYRCRSAFKL
LEVNERHQIL RPGLRVLDCG AAPGAWSQVA VQKVNAAGTD PSSPVGFVLG VDLLHIFPLE
GATFLCPADV TDPRTSQRIL EVLPGRRADV ILSDMAPNAT GFRDLDHDRL ISLCLTLLSV
TPDILQPGGT FLCKTWAGSQ SRRLQRRLTE EFQNVRIIKP EASRKESSEV YFLATQYHGR
KGTVKQ
