ID   TRNT1_MOUSE             Reviewed;         434 AA.
AC   Q8K1J6; Q3TKW1; Q3UX99; Q920N6; Q9CSX0;
DT   03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   27-MAR-2024, entry version 155.
DE   RecName: Full=CCA tRNA nucleotidyltransferase 1, mitochondrial {ECO:0000305};
DE            EC=2.7.7.72 {ECO:0000250|UniProtKB:Q96Q11};
DE   AltName: Full=mitochondrial tRNA nucleotidyl transferase, CCA-adding;
DE            Short=mt CCA-adding enzyme;
DE            Short=mt tRNA CCA-diphosphorylase;
DE            Short=mt tRNA CCA-pyrophosphorylase;
DE            Short=mt tRNA adenylyltransferase;
DE   Flags: Precursor;
GN   Name=Trnt1;
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).
RX   PubMed=11504732; DOI=10.1074/jbc.m106202200;
RA   Nagaike T., Suzuki T., Tomari Y., Takemoto-Hori C., Negayama F.,
RA   Watanabe K., Ueda T.;
RT   "Identification and characterization of mammalian mitochondrial tRNA
RT   nucleotidyltransferases.";
RL   J. Biol. Chem. 276:40041-40049(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J;
RC   TISSUE=Blastocyst, Bone marrow macrophage, Egg, and Embryo;
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 1).
RC   STRAIN=FVB/N; TISSUE=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=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas,
RC   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   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-402, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
CC   -!- FUNCTION: Nucleotidyltransferase that catalyzes the addition and repair
CC       of the essential 3'-terminal CCA sequence in tRNAs, which is necessary
CC       for the attachment of amino acids to the 3' terminus of tRNA molecules,
CC       using CTP and ATP as substrates. tRNA 3'-terminal CCA addition is
CC       required both for tRNA processing and repair. Promotes tRNA repair and
CC       recycling downstream of the ribosome-associated quality control (RQC)
CC       pathway by mediating addition of the tRNA 3'-terminal CCA following
CC       cleavage by ANKZF1 and repair by ELAC1. Also involved in tRNA
CC       surveillance by mediating tandem CCA addition to generate a CCACCA at
CC       the 3' terminus of unstable tRNAs and tRNA-like transcripts. While
CC       stable tRNAs receive only 3'-terminal CCA, unstable tRNAs beginning
CC       with GG are marked with CCACCA and rapidly degraded. The structural
CC       flexibility of RNA controls the choice between CCA versus CCACCA
CC       addition: following the first CCA addition cycle, nucleotide-binding to
CC       the active site triggers a clockwise screw motion, producing torque on
CC       the RNA. This ejects stable RNAs, whereas unstable RNAs are refolded
CC       while bound to the enzyme and subjected to a second CCA catalytic
CC       cycle. {ECO:0000250|UniProtKB:Q96Q11}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a tRNA precursor + ATP + 2 CTP = a tRNA with a 3' CCA end + 3
CC         diphosphate; Xref=Rhea:RHEA:14433, Rhea:RHEA-COMP:10465, Rhea:RHEA-
CC         COMP:10468, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563,
CC         ChEBI:CHEBI:74896, ChEBI:CHEBI:83071; EC=2.7.7.72;
CC         Evidence={ECO:0000250|UniProtKB:Q96Q11};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14434;
CC         Evidence={ECO:0000250|UniProtKB:Q96Q11};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a tRNA with a 3' CCA end + ATP + 2 CTP = a tRNA with a 3'
CC         CCACCA end + 3 diphosphate; Xref=Rhea:RHEA:76235, Rhea:RHEA-
CC         COMP:10468, Rhea:RHEA-COMP:18655, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:83071,
CC         ChEBI:CHEBI:195187; Evidence={ECO:0000250|UniProtKB:Q96Q11};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76236;
CC         Evidence={ECO:0000250|UniProtKB:Q96Q11};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:O66728};
CC   -!- SUBUNIT: Monomer, and homodimer. {ECO:0000250|UniProtKB:Q96Q11}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q96Q11}.
CC       Cytoplasm {ECO:0000250|UniProtKB:Q96Q11}. Nucleus
CC       {ECO:0000250|UniProtKB:Q96Q11}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8K1J6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8K1J6-2; Sequence=VSP_018616, VSP_018617;
CC   -!- SIMILARITY: Belongs to the tRNA nucleotidyltransferase/poly(A)
CC       polymerase family. {ECO:0000305}.
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DR   EMBL; AB063106; BAB70663.1; -; mRNA.
DR   EMBL; AK011764; BAB27827.3; -; mRNA.
DR   EMBL; AK135791; BAE22664.1; -; mRNA.
DR   EMBL; AK152739; BAE31459.1; -; mRNA.
DR   EMBL; AK166804; BAE39032.1; -; mRNA.
DR   EMBL; BC031764; AAH31764.1; -; mRNA.
DR   CCDS; CCDS20397.1; -. [Q8K1J6-1]
DR   CCDS; CCDS57443.1; -. [Q8K1J6-2]
DR   RefSeq; NP_001229287.1; NM_001242358.1. [Q8K1J6-1]
DR   RefSeq; NP_001229289.1; NM_001242360.1. [Q8K1J6-2]
DR   RefSeq; NP_081572.1; NM_027296.3. [Q8K1J6-1]
DR   RefSeq; XP_006506644.1; XM_006506581.3. [Q8K1J6-1]
DR   AlphaFoldDB; Q8K1J6; -.
DR   SMR; Q8K1J6; -.
DR   BioGRID; 213836; 2.
DR   STRING; 10090.ENSMUSP00000060900; -.
DR   iPTMnet; Q8K1J6; -.
DR   PhosphoSitePlus; Q8K1J6; -.
DR   EPD; Q8K1J6; -.
DR   MaxQB; Q8K1J6; -.
DR   PaxDb; 10090-ENSMUSP00000060900; -.
DR   PeptideAtlas; Q8K1J6; -.
DR   ProteomicsDB; 298136; -. [Q8K1J6-1]
DR   ProteomicsDB; 298137; -. [Q8K1J6-2]
DR   Pumba; Q8K1J6; -.
DR   Antibodypedia; 25074; 77 antibodies from 19 providers.
DR   DNASU; 70047; -.
DR   Ensembl; ENSMUST00000057578.16; ENSMUSP00000060900.10; ENSMUSG00000013736.17. [Q8K1J6-1]
DR   Ensembl; ENSMUST00000113247.8; ENSMUSP00000108873.2; ENSMUSG00000013736.17. [Q8K1J6-2]
DR   Ensembl; ENSMUST00000113248.4; ENSMUSP00000108874.2; ENSMUSG00000013736.17. [Q8K1J6-1]
DR   Ensembl; ENSMUST00000113249.8; ENSMUSP00000108875.2; ENSMUSG00000013736.17. [Q8K1J6-1]
DR   GeneID; 70047; -.
DR   KEGG; mmu:70047; -.
DR   UCSC; uc009dcy.2; mouse. [Q8K1J6-1]
DR   UCSC; uc029vxx.1; mouse. [Q8K1J6-2]
DR   AGR; MGI:1917297; -.
DR   CTD; 51095; -.
DR   MGI; MGI:1917297; Trnt1.
DR   VEuPathDB; HostDB:ENSMUSG00000013736; -.
DR   eggNOG; KOG2159; Eukaryota.
DR   GeneTree; ENSGT00390000009678; -.
DR   HOGENOM; CLU_015961_2_1_1; -.
DR   InParanoid; Q8K1J6; -.
DR   OMA; NLCPKPM; -.
DR   OrthoDB; 5402987at2759; -.
DR   PhylomeDB; Q8K1J6; -.
DR   TreeFam; TF313253; -.
DR   BioGRID-ORCS; 70047; 27 hits in 81 CRISPR screens.
DR   ChiTaRS; Trnt1; mouse.
DR   PRO; PR:Q8K1J6; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; Q8K1J6; Protein.
DR   Bgee; ENSMUSG00000013736; Expressed in spermatocyte and 247 other cell types or tissues.
DR   ExpressionAtlas; Q8K1J6; baseline and differential.
DR   GO; GO:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004810; F:CCA tRNA nucleotidyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0160016; F:CCACCA tRNA nucleotidyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR   GO; GO:0000049; F:tRNA binding; ISS:UniProtKB.
DR   GO; GO:1990180; P:mitochondrial tRNA 3'-end processing; ISS:UniProtKB.
DR   GO; GO:0072344; P:rescue of stalled ribosome; ISO:MGI.
DR   GO; GO:0001680; P:tRNA 3'-terminal CCA addition; ISS:UniProtKB.
DR   GO; GO:0008033; P:tRNA processing; ISO:MGI.
DR   GO; GO:0106354; P:tRNA surveillance; ISO:MGI.
DR   CDD; cd05398; NT_ClassII-CCAase; 1.
DR   Gene3D; 3.30.460.10; Beta Polymerase, domain 2; 1.
DR   Gene3D; 1.10.3090.10; cca-adding enzyme, domain 2; 1.
DR   InterPro; IPR043519; NT_sf.
DR   InterPro; IPR002646; PolA_pol_head_dom.
DR   InterPro; IPR032828; PolyA_RNA-bd.
DR   PANTHER; PTHR46173; CCA TRNA NUCLEOTIDYLTRANSFERASE 1, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR46173:SF1; CCA TRNA NUCLEOTIDYLTRANSFERASE 1, MITOCHONDRIAL; 1.
DR   Pfam; PF01743; PolyA_pol; 1.
DR   Pfam; PF12627; PolyA_pol_RNAbd; 1.
DR   SUPFAM; SSF81301; Nucleotidyltransferase; 1.
DR   SUPFAM; SSF81891; Poly A polymerase C-terminal region-like; 1.
DR   Genevisible; Q8K1J6; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; ATP-binding; Cytoplasm; Magnesium;
KW   Metal-binding; Mitochondrion; Nucleotide-binding; Nucleotidyltransferase;
KW   Nucleus; Phosphoprotein; Reference proteome; RNA-binding; Transferase;
KW   Transit peptide; tRNA processing.
FT   TRANSIT         1..41
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           42..434
FT                   /note="CCA tRNA nucleotidyltransferase 1, mitochondrial"
FT                   /id="PRO_0000004783"
FT   BINDING         64
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         64
FT                   /ligand="CTP"
FT                   /ligand_id="ChEBI:CHEBI:37563"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         67
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         67
FT                   /ligand="CTP"
FT                   /ligand_id="ChEBI:CHEBI:37563"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         77
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:O66728"
FT   BINDING         79
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250|UniProtKB:O66728"
FT   BINDING         151
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         151
FT                   /ligand="CTP"
FT                   /ligand_id="ChEBI:CHEBI:37563"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         194
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         194
FT                   /ligand="CTP"
FT                   /ligand_id="ChEBI:CHEBI:37563"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         197
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         197
FT                   /ligand="CTP"
FT                   /ligand_id="ChEBI:CHEBI:37563"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         200
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         200
FT                   /ligand="CTP"
FT                   /ligand_id="ChEBI:CHEBI:37563"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         203
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   BINDING         203
FT                   /ligand="CTP"
FT                   /ligand_id="ChEBI:CHEBI:37563"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   SITE            152
FT                   /note="May assist in discriminating ATP from CTP"
FT                   /evidence="ECO:0000250|UniProtKB:Q7SIB1"
FT   SITE            193
FT                   /note="Involved in nucleotide selection"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         400
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96Q11"
FT   MOD_RES         402
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   VAR_SEQ         204..215
FT                   /note="FYGRIVDRPGDH -> PGIVLGDLTTEK (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_018616"
FT   VAR_SEQ         216..434
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_018617"
FT   CONFLICT        202
FT                   /note="F -> I (in Ref. 1; BAB70663)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   434 AA;  49895 MW;  0578FB438165838B CRC64;
     MQSVLYPWHR QVLRCSWSRL CLLKRYLFTM KLQSPEFQSL FTEGLKSLTE LFAKENHELR
     IAGGAVRDLL NGVKPQDVDF ATTATPTQMK EMFQSAGIRM INNKGEKHGT ITARLHEENF
     EVTTLRIDVT TDGRHAEVEF TTDWQKDAER RDLTINSMFL GFDGTLFDYF NGYADLKNKK
     VRFVGHAKQR IQEDYLRILR YFRFYGRIVD RPGDHDHETL EAIAENAKGL AGISGERIWV
     ELKKILTGDH VNHLIHLIYD LGVAPHIGLP ANANLEEFNK VSKNVEGFSP KPMTLLASLF
     KVQDDVTKLD LRLKISKEEK NLGLFIVKNR KDLIKATDSS EPLKPYQDFV IDSREPDATA
     RVCELLKYQG EHGLLKEMQQ WSVPPFPVSG HDIRKVGISS GKEIGALLQQ LREQWKKSGY
     RMEKDELLSY IKKT
//