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THUM3_MOUSE
ID   THUM3_MOUSE             Reviewed;         505 AA.
AC   P97770; Q99M45; Q9D3P0;
DT   14-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   03-AUG-2022, entry version 138.
DE   RecName: Full=tRNA (guanine(6)-N2)-methyltransferase THUMP3 {ECO:0000305};
DE            EC=2.1.1.256 {ECO:0000250|UniProtKB:Q9BV44};
DE   AltName: Full=GtROSA26asSor {ECO:0000312|MGI:MGI:1277973};
DE   AltName: Full=THUMP domain-containing protein 3 {ECO:0000303|PubMed:34669960};
GN   Name=Thumpd3;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX   PubMed=9108056; DOI=10.1073/pnas.94.8.3789;
RA   Zambrowicz B.P., Imamoto A., Fiering S., Herzenberg L.A., Kerr W.G.,
RA   Soriano P.;
RT   "Disruption of overlapping transcripts in the ROSA beta geo 26 gene trap
RT   strain leads to widespread expression of beta-galactosidase in mouse
RT   embryos and hematopoietic cells.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:3789-3794(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC   STRAIN=C57BL/6J; TISSUE=Eye, and Head;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, and Mammary gland;
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   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [5]
RP   TISSUE SPECIFICITY.
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 (By
CC       similarity). Also catalyzes the formation of N(2)-methylguanosine at
CC       position 7 of tRNA(Trp) (By similarity). Requires the methyltransferase
CC       adapter protein TRM112 for tRNA methyltransferase activity (By
CC       similarity). {ECO:0000250|UniProtKB:Q9BV44}.
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:0000250|UniProtKB:Q9BV44};
CC   -!- SUBUNIT: Interacts with TRMT112; the interaction is direct and is
CC       required for THUMPD3 methyltransferase activity.
CC       {ECO:0000250|UniProtKB:Q9BV44}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9BV44}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P97770-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P97770-2; Sequence=VSP_021537;
CC       Name=3;
CC         IsoId=P97770-3; Sequence=VSP_021538;
CC   -!- TISSUE SPECIFICITY: Ubiquitously expressed (PubMed:9108056). Abundantly
CC       expressed in the testis, also expressed in the brain, heart, kidney,
CC       liver, lung, muscle and spleen (PubMed:34669960).
CC       {ECO:0000269|PubMed:34669960, ECO:0000269|PubMed:9108056}.
CC   -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC       {ECO:0000305}.
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DR   EMBL; U83176; AAC60384.1; -; mRNA.
DR   EMBL; AK017246; BAB30650.1; -; mRNA.
DR   EMBL; AK142140; BAE24945.1; -; mRNA.
DR   EMBL; BC002024; AAH02024.1; -; mRNA.
DR   EMBL; BC012688; AAH12688.1; -; mRNA.
DR   EMBL; BC046800; AAH46800.1; -; mRNA.
DR   CCDS; CCDS20410.1; -. [P97770-1]
DR   RefSeq; NP_032214.1; NM_008188.2. [P97770-1]
DR   RefSeq; XP_006505640.1; XM_006505577.3.
DR   RefSeq; XP_006505641.1; XM_006505578.2. [P97770-1]
DR   RefSeq; XP_006505642.1; XM_006505579.1. [P97770-1]
DR   AlphaFoldDB; P97770; -.
DR   SMR; P97770; -.
DR   BioGRID; 200120; 2.
DR   STRING; 10090.ENSMUSP00000032398; -.
DR   iPTMnet; P97770; -.
DR   PhosphoSitePlus; P97770; -.
DR   EPD; P97770; -.
DR   MaxQB; P97770; -.
DR   PaxDb; P97770; -.
DR   PeptideAtlas; P97770; -.
DR   PRIDE; P97770; -.
DR   ProteomicsDB; 262983; -. [P97770-1]
DR   ProteomicsDB; 262984; -. [P97770-2]
DR   ProteomicsDB; 262985; -. [P97770-3]
DR   Antibodypedia; 25366; 142 antibodies from 25 providers.
DR   DNASU; 14911; -.
DR   Ensembl; ENSMUST00000032398; ENSMUSP00000032398; ENSMUSG00000030264. [P97770-1]
DR   GeneID; 14911; -.
DR   KEGG; mmu:14911; -.
DR   UCSC; uc009dek.1; mouse. [P97770-1]
DR   CTD; 25917; -.
DR   MGI; MGI:1277973; Thumpd3.
DR   VEuPathDB; HostDB:ENSMUSG00000030264; -.
DR   eggNOG; ENOG502QSE5; Eukaryota.
DR   GeneTree; ENSGT00530000063557; -.
DR   HOGENOM; CLU_045692_0_0_1; -.
DR   InParanoid; P97770; -.
DR   OMA; YFEVPAR; -.
DR   OrthoDB; 674030at2759; -.
DR   PhylomeDB; P97770; -.
DR   TreeFam; TF313093; -.
DR   BioGRID-ORCS; 14911; 1 hit in 71 CRISPR screens.
DR   PRO; PR:P97770; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; P97770; protein.
DR   Bgee; ENSMUSG00000030264; Expressed in choroid plexus epithelium and 269 other tissues.
DR   ExpressionAtlas; P97770; baseline and differential.
DR   Genevisible; P97770; MM.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005730; C:nucleolus; ISO:MGI.
DR   GO; GO:0016423; F:tRNA (guanine) methyltransferase activity; IBA:GO_Central.
DR   GO; GO:0004809; F:tRNA (guanine-N2-)-methyltransferase activity; ISS: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; ISS: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   Alternative splicing; Cytoplasm; Methyltransferase; Reference proteome;
KW   RNA-binding; S-adenosyl-L-methionine; Transferase; tRNA processing;
KW   tRNA-binding.
FT   CHAIN           1..505
FT                   /note="tRNA (guanine(6)-N2)-methyltransferase THUMP3"
FT                   /id="PRO_0000259770"
FT   DOMAIN          171..287
FT                   /note="THUMP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00529"
FT   REGION          145..182
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        153..182
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..3
FT                   /note="MSC -> MS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_021537"
FT   VAR_SEQ         316..505
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_021538"
FT   CONFLICT        8
FT                   /note="A -> T (in Ref. 3; AAH02024/AAH12688)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        266
FT                   /note="T -> N (in Ref. 2; BAB30650)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        380
FT                   /note="T -> S (in Ref. 3; AAH02024/AAH12688)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   505 AA;  56431 MW;  6DA0F4C5B768C541 CRC64;
     MSCDTQEATR ECLGMNLDGN KEPVSLVESG VRSESEHLQV TIGATVPTGF EQTAAGEVRE
     KLKSACRISK DRGKIYFDIA VESLAQVHCL RSVDNLFVVV QEFKDYQFKD TKEEVLRDFE
     ELAGKLPWSD PLKVWQINTT FKKKKAKRRK ANQSAGKEKA DCGQGDKADE KDGKKKHASS
     TSDSHILDYY ENPAIKEEIS TLVGDVLSSC KDETGQSLRE ETEPQVQKFR VTCNRAGEKH
     CFTSNEAARD FGGAIQEYFK WKADMTNFDV EVLLNIHDNE VIVAIALTEE SLHRRNITHF
     GPTTLRSTLA YGMLRLCEPK PTDVIVDPMC GTGAIPIEGA TEWSHCYHIA GDNNPLAVNR
     AANNISSLLT KSQIKDGKTT WGLPIDAVQW DICNLPLRTA SVDIIVTDMP FGKRMGSKKR
     NWNLYPACLR EMSRVCRPGT GRAVLLTQDK KCFTKALSGM GHVWRKVHVV WVNIGGLHAA
     VYLLKRTAQA FVHPSDQDEG RDPPW
 
 
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