THUM3_HUMAN
ID THUM3_HUMAN Reviewed; 507 AA.
AC Q9BV44; Q9H8V6; Q9NVC1; Q9UFS3;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=tRNA (guanine(6)-N2)-methyltransferase THUMP3 {ECO:0000305};
DE EC=2.1.1.256 {ECO:0000269|PubMed:34669960};
DE AltName: Full=THUMP domain-containing protein 3 {ECO:0000303|PubMed:34669960};
GN Name=THUMPD3;
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], AND VARIANT GLN-459.
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 MRNA].
RC TISSUE=Eye, and Placenta;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 144-507.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [6]
RP INTERACTION WITH TRMT112, AND SUBCELLULAR LOCATION.
RX PubMed=34948388; DOI=10.3390/ijms222413593;
RA Brumele B., Mutso M., Telanne L., Ounap K., Spunde K., Abroi A., Kurg R.;
RT "Human TRMT112-Methyltransferase Network Consists of Seven Partners
RT Interacting with a Common Co-Factor.";
RL Int. J. Mol. Sci. 22:13593-13593(2021).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH TRMT112, AND SUBCELLULAR
RP LOCATION.
RX PubMed=34669960; DOI=10.1093/nar/gkab927;
RA Yang W.Q., Xiong Q.P., Ge J.Y., Li H., Zhu W.Y., Nie Y., Lin X., Lv D.,
RA Li J., Lin H., Liu R.J.;
RT "THUMPD3-TRMT112 is a m2G methyltransferase working on a broad range of
RT tRNA substrates.";
RL Nucleic Acids Res. 49:11900-11919(2021).
CC -!- FUNCTION: Methyltransferase which catalyzes the formation of N(2)-
CC methylguanosine at position 6 in a broad range of tRNA substrates
CC containing the characteristic 3'-CCA terminus of mature tRNAs
CC (PubMed:34669960). Also catalyzes the formation of N(2)-methylguanosine
CC at position 7 of tRNA(Trp) (PubMed:34669960). Requires the
CC methyltransferase adapter protein TRM112 for tRNA methyltransferase
CC activity (PubMed:34669960). {ECO:0000269|PubMed:34669960}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanosine(6) in tRNA + S-adenosyl-L-methionine = H(+) + N(2)-
CC methylguanosine(6) in tRNA + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:51116, Rhea:RHEA-COMP:12888, Rhea:RHEA-COMP:12889,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:74269, ChEBI:CHEBI:74481; EC=2.1.1.256;
CC Evidence={ECO:0000269|PubMed:34669960};
CC -!- SUBUNIT: Interacts with TRMT112; the interaction is direct and is
CC required for THUMPD3 methyltransferase activity.
CC {ECO:0000269|PubMed:34669960, ECO:0000269|PubMed:34948388}.
CC -!- INTERACTION:
CC Q9BV44; Q9UI30: TRMT112; NbExp=4; IntAct=EBI-373253, EBI-373326;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:34669960,
CC ECO:0000269|PubMed:34948388}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
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DR EMBL; AK001680; BAA91832.1; -; mRNA.
DR EMBL; AK023263; BAB14495.1; -; mRNA.
DR EMBL; BC001622; AAH01622.1; -; mRNA.
DR EMBL; BC010421; AAH10421.1; -; mRNA.
DR EMBL; AL117483; CAB55956.1; -; mRNA.
DR CCDS; CCDS2573.1; -.
DR PIR; T17266; T17266.
DR RefSeq; NP_001107564.1; NM_001114092.1.
DR RefSeq; NP_056268.2; NM_015453.2.
DR RefSeq; XP_005265078.1; XM_005265021.4.
DR RefSeq; XP_005265079.1; XM_005265022.4.
DR RefSeq; XP_005265080.1; XM_005265023.3.
DR RefSeq; XP_005265081.1; XM_005265024.4.
DR RefSeq; XP_006713149.1; XM_006713086.3.
DR RefSeq; XP_011531872.1; XM_011533570.2.
DR AlphaFoldDB; Q9BV44; -.
DR SMR; Q9BV44; -.
DR BioGRID; 117420; 84.
DR IntAct; Q9BV44; 23.
DR STRING; 9606.ENSP00000339532; -.
DR GlyGen; Q9BV44; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9BV44; -.
DR PhosphoSitePlus; Q9BV44; -.
DR BioMuta; THUMPD3; -.
DR DMDM; 74733286; -.
DR EPD; Q9BV44; -.
DR jPOST; Q9BV44; -.
DR MassIVE; Q9BV44; -.
DR MaxQB; Q9BV44; -.
DR PaxDb; Q9BV44; -.
DR PeptideAtlas; Q9BV44; -.
DR PRIDE; Q9BV44; -.
DR ProteomicsDB; 79168; -.
DR Antibodypedia; 25366; 142 antibodies from 25 providers.
DR DNASU; 25917; -.
DR Ensembl; ENST00000345094.7; ENSP00000339532.3; ENSG00000134077.16.
DR Ensembl; ENST00000452837.7; ENSP00000395893.2; ENSG00000134077.16.
DR Ensembl; ENST00000515662.6; ENSP00000424064.1; ENSG00000134077.16.
DR GeneID; 25917; -.
DR KEGG; hsa:25917; -.
DR MANE-Select; ENST00000452837.7; ENSP00000395893.2; NM_001114092.2; NP_001107564.1.
DR UCSC; uc003brn.5; human.
DR CTD; 25917; -.
DR DisGeNET; 25917; -.
DR GeneCards; THUMPD3; -.
DR HGNC; HGNC:24493; THUMPD3.
DR HPA; ENSG00000134077; Low tissue specificity.
DR neXtProt; NX_Q9BV44; -.
DR OpenTargets; ENSG00000134077; -.
DR PharmGKB; PA134969445; -.
DR VEuPathDB; HostDB:ENSG00000134077; -.
DR eggNOG; ENOG502QSE5; Eukaryota.
DR GeneTree; ENSGT00530000063557; -.
DR HOGENOM; CLU_045692_0_0_1; -.
DR InParanoid; Q9BV44; -.
DR OMA; YFEVPAR; -.
DR OrthoDB; 674030at2759; -.
DR PhylomeDB; Q9BV44; -.
DR TreeFam; TF313093; -.
DR PathwayCommons; Q9BV44; -.
DR SignaLink; Q9BV44; -.
DR BioGRID-ORCS; 25917; 9 hits in 1078 CRISPR screens.
DR ChiTaRS; THUMPD3; human.
DR GenomeRNAi; 25917; -.
DR Pharos; Q9BV44; Tdark.
DR PRO; PR:Q9BV44; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9BV44; protein.
DR Bgee; ENSG00000134077; Expressed in sperm and 181 other tissues.
DR ExpressionAtlas; Q9BV44; baseline and differential.
DR Genevisible; Q9BV44; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0016423; F:tRNA (guanine) methyltransferase activity; IBA:GO_Central.
DR GO; GO:0004809; F:tRNA (guanine-N2-)-methyltransferase activity; IMP:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-KW.
DR GO; GO:0030488; P:tRNA methylation; IBA:GO_Central.
DR GO; GO:0002940; P:tRNA N2-guanine methylation; IMP:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR000241; RNA_methylase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR004114; THUMP_dom.
DR Pfam; PF02926; THUMP; 1.
DR Pfam; PF01170; UPF0020; 1.
DR SMART; SM00981; THUMP; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51165; THUMP; 1.
DR PROSITE; PS01261; UPF0020; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Methyltransferase; Reference proteome; RNA-binding;
KW S-adenosyl-L-methionine; Transferase; tRNA processing; tRNA-binding.
FT CHAIN 1..507
FT /note="tRNA (guanine(6)-N2)-methyltransferase THUMP3"
FT /id="PRO_0000259769"
FT DOMAIN 165..285
FT /note="THUMP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00529"
FT VARIANT 459
FT /note="R -> Q (in dbSNP:rs1129174)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_028976"
FT CONFLICT 499
FT /note="R -> S (in Ref. 1; BAA91832)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 507 AA; 57003 MW; 0CE5587AEE817C19 CRC64;
MCDIEEATNQ LLDVNLHENQ KSVQVTESDL GSESELLVTI GATVPTGFEQ TAADEVREKL
GSSCKISRDR GKIYFVISVE SLAQVHCLRS VDNLFVVVQE FQDYQFKQTK EEVLKDFEDL
AGKLPWSNPL KVWKINASFK KKKAKRKKIN QNSSKEKINN GQEVKIDQRN VKKEFTSHAL
DSHILDYYEN PAIKEDVSTL IGDDLASCKD ETDESSKEET EPQVLKFRVT CNRAGEKHCF
TSNEAARDFG GAVQDYFKWK ADMTNFDVEV LLNIHDNEVI VGIALTEESL HRRNITHFGP
TTLRSTLAYG MLRLCDPLPY DIIVDPMCGT GAIPIEGATE WSDCFHIAGD NNPLAVNRAA
NNIASLLTKS QIKEGKPSWG LPIDAVQWDI CNLPLRTGSV DIIVTDLPFG KRMGSKKRNW
NLYPACLREM SRVCTPTTGR AVLLTQDTKC FTKALSGMRH VWRKVDTVWV NVGGLRAAVY
VLIRTPQAFV HPSEQDGERG TLWQCKE
