TM10A_HUMAN
ID TM10A_HUMAN Reviewed; 339 AA.
AC Q8TBZ6; B2R8X7; Q9Y2T9;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=tRNA methyltransferase 10 homolog A;
DE EC=2.1.1.221 {ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:25053765};
DE AltName: Full=RNA (guanine-9-)-methyltransferase domain-containing protein 2;
DE AltName: Full=tRNA (guanine(9)-N(1))-methyltransferase TRMT10A;
GN Name=TRMT10A; Synonyms=RG9MTD2;
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 [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 107-339.
RA Ji Y., Huang T., Johnson B.H., Thompson E.B.;
RT "Homo sapiens cDNA clone 44 from HTLV-1 transformed lymphocyte library.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23042678; DOI=10.1093/nar/gks910;
RA Vilardo E., Nachbagauer C., Buzet A., Taschner A., Holzmann J.,
RA Rossmanith W.;
RT "A subcomplex of human mitochondrial RNase P is a bifunctional
RT methyltransferase--extensive moonlighting in mitochondrial tRNA
RT biogenesis.";
RL Nucleic Acids Res. 40:11583-11593(2012).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-336, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP INVOLVEMENT IN MSSGM1, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=24204302; DOI=10.1371/journal.pgen.1003888;
RA Igoillo-Esteve M., Genin A., Lambert N., Desir J., Pirson I.,
RA Abdulkarim B., Simonis N., Drielsma A., Marselli L., Marchetti P.,
RA Vanderhaeghen P., Eizirik D.L., Wuyts W., Julier C., Chakera A.J.,
RA Ellard S., Hattersley A.T., Abramowicz M., Cnop M.;
RT "tRNA methyltransferase homolog gene TRMT10A mutation in young onset
RT diabetes and primary microcephaly in humans.";
RL PLoS Genet. 9:E1003888-E1003888(2013).
RN [8]
RP FUNCTION, INTERACTION WITH TRANSFER RNA, INVOLVEMENT IN MSSGM1, VARIANT
RP MSSGM1 ARG-206, AND CHARACTERIZATION OF VARIANT MSSGM1 ARG-206.
RX PubMed=25053765; DOI=10.1136/jmedgenet-2014-102282;
RA Gillis D., Krishnamohan A., Yaacov B., Shaag A., Jackman J.E., Elpeleg O.;
RT "TRMT10A dysfunction is associated with abnormalities in glucose
RT homeostasis, short stature and microcephaly.";
RL J. Med. Genet. 51:581-586(2014).
RN [9]
RP VARIANT [LARGE SCALE ANALYSIS] GLN-82.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [10]
RP VARIANTS MSSGM1 93-ARG--HIS-339 DEL AND 133-ARG--HIS-339 DEL.
RX PubMed=26535115; DOI=10.12688/f1000research.7106.1;
RG C4RCD Research Group;
RA Narayanan M., Ramsey K., Grebe T., Schrauwen I., Szelinger S.,
RA Huentelman M., Craig D., Narayanan V.;
RT "Case Report: Compound heterozygous nonsense mutations in TRMT10A are
RT associated with microcephaly, delayed development, and periventricular
RT white matter hyperintensities.";
RL F1000Research 4:912-912(2015).
RN [11]
RP VARIANT MSSGM1 27-GLU--HIS-339 DEL.
RX PubMed=26526202; DOI=10.1111/dme.13024;
RA Yew T.W., McCreight L., Colclough K., Ellard S., Pearson E.R.;
RT "tRNA methyltransferase homologue gene TRMT10A mutation in young adult-
RT onset diabetes with intellectual disability, microcephaly and epilepsy.";
RL Diabet. Med. 33:E21-E25(2016).
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent guanine N(1)-
CC methyltransferase that catalyzes the formation of N(1)-methylguanine at
CC position 9 (m1G9) in tRNAs (PubMed:23042678, PubMed:25053765). Probably
CC not able to catalyze formation of N(1)-methyladenine at position 9
CC (m1A9) in tRNAs (PubMed:23042678). {ECO:0000269|PubMed:23042678,
CC ECO:0000269|PubMed:25053765}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanosine(9) in tRNA + S-adenosyl-L-methionine = H(+) + N(1)-
CC methylguanosine(9) in tRNA + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:43156, Rhea:RHEA-COMP:10367, Rhea:RHEA-COMP:10368,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:73542, ChEBI:CHEBI:74269; EC=2.1.1.221;
CC Evidence={ECO:0000269|PubMed:23042678, ECO:0000269|PubMed:25053765};
CC -!- SUBUNIT: Interacts with tRNA. {ECO:0000269|PubMed:25053765}.
CC -!- INTERACTION:
CC Q8TBZ6; Q9C029: TRIM7; NbExp=3; IntAct=EBI-11059925, EBI-2813981;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24204302}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:24204302}.
CC -!- TISSUE SPECIFICITY: Expressed in embryonic and fetal brain. It is
CC expressed throughout the dorsal telencephalon at 8 and 11 weeks of
CC gestation, with highest expression in ventricular zone and marginal
CC zone. Detected in cerebellar cortex and nuclei, but not in dorsal
CC telencephalon, at later stages. {ECO:0000269|PubMed:24204302}.
CC -!- DISEASE: Microcephaly, short stature, and impaired glucose metabolism 1
CC (MSSGM1) [MIM:616033]: An autosomal recessive disease characterized by
CC microcephaly, intellectual disability, short stature, and disturbed
CC glucose metabolism. Additional clinical features include delayed
CC puberty, hypoglycemia-related seizures, hyperinsulinemic hypoglycemia,
CC and early-onset diabetes. {ECO:0000269|PubMed:24204302,
CC ECO:0000269|PubMed:25053765, ECO:0000269|PubMed:26526202,
CC ECO:0000269|PubMed:26535115}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class IV-like SAM-binding methyltransferase
CC superfamily. TRM10 family. {ECO:0000255|PROSITE-ProRule:PRU01012}.
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DR EMBL; AK313548; BAG36324.1; -; mRNA.
DR EMBL; CH471057; EAX06104.1; -; Genomic_DNA.
DR EMBL; BC028373; AAH28373.1; -; mRNA.
DR EMBL; AF106046; AAD21019.1; -; mRNA.
DR CCDS; CCDS3650.1; -.
DR RefSeq; NP_001128137.1; NM_001134665.2.
DR RefSeq; NP_001128138.1; NM_001134666.2.
DR RefSeq; NP_689505.1; NM_152292.4.
DR RefSeq; XP_005263409.1; XM_005263352.3.
DR RefSeq; XP_006714480.1; XM_006714417.2.
DR PDB; 4FMW; X-ray; 2.00 A; A/B=82-277.
DR PDBsum; 4FMW; -.
DR AlphaFoldDB; Q8TBZ6; -.
DR SMR; Q8TBZ6; -.
DR BioGRID; 125035; 16.
DR IntAct; Q8TBZ6; 7.
DR STRING; 9606.ENSP00000273962; -.
DR iPTMnet; Q8TBZ6; -.
DR PhosphoSitePlus; Q8TBZ6; -.
DR BioMuta; TRMT10A; -.
DR DMDM; 74730533; -.
DR EPD; Q8TBZ6; -.
DR jPOST; Q8TBZ6; -.
DR MassIVE; Q8TBZ6; -.
DR PaxDb; Q8TBZ6; -.
DR PeptideAtlas; Q8TBZ6; -.
DR PRIDE; Q8TBZ6; -.
DR ProteomicsDB; 74061; -.
DR Antibodypedia; 14880; 90 antibodies from 17 providers.
DR DNASU; 93587; -.
DR Ensembl; ENST00000273962.7; ENSP00000273962.3; ENSG00000145331.14.
DR Ensembl; ENST00000394876.7; ENSP00000378342.2; ENSG00000145331.14.
DR Ensembl; ENST00000394877.7; ENSP00000378343.3; ENSG00000145331.14.
DR GeneID; 93587; -.
DR KEGG; hsa:93587; -.
DR MANE-Select; ENST00000394876.7; ENSP00000378342.2; NM_001134665.3; NP_001128137.1.
DR CTD; 93587; -.
DR DisGeNET; 93587; -.
DR GeneCards; TRMT10A; -.
DR HGNC; HGNC:28403; TRMT10A.
DR HPA; ENSG00000145331; Low tissue specificity.
DR MalaCards; TRMT10A; -.
DR MIM; 616013; gene.
DR MIM; 616033; phenotype.
DR neXtProt; NX_Q8TBZ6; -.
DR OpenTargets; ENSG00000145331; -.
DR Orphanet; 391408; Primary microcephaly-mild intellectual disability-young-onset diabetes syndrome.
DR PharmGKB; PA134979919; -.
DR VEuPathDB; HostDB:ENSG00000145331; -.
DR eggNOG; KOG2967; Eukaryota.
DR GeneTree; ENSGT00530000063169; -.
DR HOGENOM; CLU_034384_7_0_1; -.
DR InParanoid; Q8TBZ6; -.
DR OMA; FKKNDGW; -.
DR OrthoDB; 1396299at2759; -.
DR PhylomeDB; Q8TBZ6; -.
DR TreeFam; TF330972; -.
DR BRENDA; 2.1.1.221; 2681.
DR PathwayCommons; Q8TBZ6; -.
DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol.
DR SignaLink; Q8TBZ6; -.
DR BioGRID-ORCS; 93587; 31 hits in 1073 CRISPR screens.
DR GenomeRNAi; 93587; -.
DR Pharos; Q8TBZ6; Tbio.
DR PRO; PR:Q8TBZ6; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8TBZ6; protein.
DR Bgee; ENSG00000145331; Expressed in calcaneal tendon and 135 other tissues.
DR ExpressionAtlas; Q8TBZ6; baseline and differential.
DR Genevisible; Q8TBZ6; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:CAFA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0052905; F:tRNA (guanine(9)-N(1))-methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0009019; F:tRNA (guanine-N1-)-methyltransferase activity; IDA:CAFA.
DR GO; GO:0000049; F:tRNA binding; IDA:UniProtKB.
DR GO; GO:0030488; P:tRNA methylation; IDA:UniProtKB.
DR GO; GO:0002939; P:tRNA N1-guanine methylation; IMP:UniProtKB.
DR Gene3D; 3.40.1280.30; -; 1.
DR InterPro; IPR028564; MT_TRM10-typ.
DR InterPro; IPR038459; MT_TRM10-typ_sf.
DR InterPro; IPR016653; TRM10/TRM10A.
DR InterPro; IPR007356; tRNA_m1G_MeTrfase_euk.
DR InterPro; IPR016009; tRNA_MeTrfase_TRMD/TRM10.
DR PANTHER; PTHR13563; PTHR13563; 1.
DR PANTHER; PTHR13563:SF13; PTHR13563:SF13; 1.
DR Pfam; PF01746; tRNA_m1G_MT; 1.
DR PIRSF; PIRSF016323; tRNA_m1G_mtfrase_met; 1.
DR PROSITE; PS51675; SAM_MT_TRM10; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Diabetes mellitus; Disease variant; Dwarfism;
KW Intellectual disability; Methyltransferase; Nucleus; Phosphoprotein;
KW Reference proteome; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..339
FT /note="tRNA methyltransferase 10 homolog A"
FT /id="PRO_0000311315"
FT DOMAIN 89..279
FT /note="SAM-dependent MTase TRM10-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01012"
FT REGION 1..90
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 282..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 52..81
FT /evidence="ECO:0000255"
FT COMPBIAS 17..62
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 74..90
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 292..332
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 336
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 27..339
FT /note="Missing (in MSSGM1)"
FT /evidence="ECO:0000269|PubMed:26526202"
FT /id="VAR_080046"
FT VARIANT 82
FT /note="P -> Q (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_037222"
FT VARIANT 93..339
FT /note="Missing (in MSSGM1)"
FT /evidence="ECO:0000269|PubMed:26535115"
FT /id="VAR_080047"
FT VARIANT 133..339
FT /note="Missing (in MSSGM1)"
FT /evidence="ECO:0000269|PubMed:26535115"
FT /id="VAR_080048"
FT VARIANT 133
FT /note="R -> Q (in dbSNP:rs10007569)"
FT /id="VAR_037223"
FT VARIANT 206
FT /note="G -> R (in MSSGM1; results in loss of activity; does
FT not affect affinity for Gly-tRNA; dbSNP:rs587777744)"
FT /evidence="ECO:0000269|PubMed:25053765"
FT /id="VAR_072420"
FT CONFLICT 292
FT /note="N -> F (in Ref. 4; AAD21019)"
FT /evidence="ECO:0000305"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:4FMW"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:4FMW"
FT HELIX 115..134
FT /evidence="ECO:0007829|PDB:4FMW"
FT STRAND 140..145
FT /evidence="ECO:0007829|PDB:4FMW"
FT HELIX 148..157
FT /evidence="ECO:0007829|PDB:4FMW"
FT HELIX 159..162
FT /evidence="ECO:0007829|PDB:4FMW"
FT HELIX 174..177
FT /evidence="ECO:0007829|PDB:4FMW"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:4FMW"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:4FMW"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:4FMW"
FT HELIX 217..225
FT /evidence="ECO:0007829|PDB:4FMW"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:4FMW"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:4FMW"
FT HELIX 248..261
FT /evidence="ECO:0007829|PDB:4FMW"
FT HELIX 264..271
FT /evidence="ECO:0007829|PDB:4FMW"
SQ SEQUENCE 339 AA; 39719 MW; 1FCDA258DD7CA04D CRC64;
MSSEMLPAFI ETSNVDKKQG INEDQEESQK PRLGEGCEPI SKRQMKKLIK QKQWEEQREL
RKQKRKEKRK RKKLERQCQM EPNSDGHDRK RVRRDVVHST LRLIIDCSFD HLMVLKDIKK
LHKQIQRCYA ENRRALHPVQ FYLTSHGGQL KKNMDENDKG WVNWKDIHIK PEHYSELIKK
EDLIYLTSDS PNILKELDES KAYVIGGLVD HNHHKGLTYK QASDYGINHA QLPLGNFVKM
NSRKVLAVNH VFEIILEYLE TRDWQEAFFT ILPQRKGAVP TDKACESASH DNQSVRMEEG
GSDSDSSEEE YSRNELDSPH EEKQDKENHT ESTVNSLPH
