ID   CCA1_YEAST              Reviewed;         546 AA.
AC   P21269; D3DM76;
DT   01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1991, sequence version 1.
DT   27-MAR-2024, entry version 187.
DE   RecName: Full=CCA tRNA nucleotidyltransferase, mitochondrial;
DE            EC=2.7.7.72 {ECO:0000269|PubMed:1634528};
DE   AltName: Full=CCA-adding enzyme;
DE   AltName: Full=tRNA CCA-pyrophosphorylase;
DE   AltName: Full=tRNA adenylyltransferase;
DE   AltName: Full=tRNA nucleotidyltransferase;
DE   Flags: Precursor;
GN   Name=CCA1; Synonyms=TNT1; OrderedLocusNames=YER168C;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2204621; DOI=10.1016/s0021-9258(17)46210-7;
RA   Aebi M., Kirchner G., Chen J.Y., Vijayraghavan U., Jacobson A.,
RA   Martin N.C., Abelson J.;
RT   "Isolation of a temperature-sensitive mutant with an altered tRNA
RT   nucleotidyltransferase and cloning of the gene encoding tRNA
RT   nucleotidyltransferase in the yeast Saccharomyces cerevisiae.";
RL   J. Biol. Chem. 265:16216-16220(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169868;
RA   Dietrich F.S., Mulligan J.T., Hennessy K.M., Yelton M.A., Allen E.,
RA   Araujo R., Aviles E., Berno A., Brennan T., Carpenter J., Chen E.,
RA   Cherry J.M., Chung E., Duncan M., Guzman E., Hartzell G., Hunicke-Smith S.,
RA   Hyman R.W., Kayser A., Komp C., Lashkari D., Lew H., Lin D., Mosedale D.,
RA   Nakahara K., Namath A., Norgren R., Oefner P., Oh C., Petel F.X.,
RA   Roberts D., Sehl P., Schramm S., Shogren T., Smith V., Taylor P., Wei Y.,
RA   Botstein D., Davis R.W.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome V.";
RL   Nature 387:78-81(1997).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   ALTERNATIVE INITIATION, PROTEIN SEQUENCE OF 19-26, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=8175766; DOI=10.1016/s0021-9258(17)36841-2;
RA   Wolfe C.L., Lou Y.-C., Hopper A.K., Martin N.C.;
RT   "Interplay of heterogeneous transcriptional start sites and translational
RT   selection of AUGs dictate the production of mitochondrial and
RT   cytosolic/nuclear tRNA nucleotidyltransferase from the same gene in
RT   yeast.";
RL   J. Biol. Chem. 269:13361-13366(1994).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX   PubMed=1634528; DOI=10.1016/s0021-9258(18)42122-9;
RA   Chen J.Y., Joyce P.B., Wolfe C.L., Steffen M.C., Martin N.C.;
RT   "Cytoplasmic and mitochondrial tRNA nucleotidyltransferase activities are
RT   derived from the same gene in the yeast Saccharomyces cerevisiae.";
RL   J. Biol. Chem. 267:14879-14883(1992).
RN   [6]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [7]
RP   FUNCTION, AND MUTAGENESIS OF ARG-64 AND GLU-189.
RX   PubMed=23872483; DOI=10.1016/j.bbapap.2013.07.003;
RA   Goring M.E., Leibovitch M., Gea-Mallorqui E., Karls S., Richard F.,
RA   Hanic-Joyce P.J., Joyce P.B.;
RT   "The ability of an arginine to tryptophan substitution in Saccharomyces
RT   cerevisiae tRNA nucleotidyltransferase to alleviate a temperature-sensitive
RT   phenotype suggests a role for motif C in active site organization.";
RL   Biochim. Biophys. Acta 1834:2097-2106(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 (PubMed:1634528, PubMed:23872483). tRNA
CC       3'-terminal CCA addition is required both for tRNA processing and
CC       repair (By similarity). Also involved in tRNA surveillance by mediating
CC       tandem CCA addition to generate a CCACCA at the 3' terminus of unstable
CC       tRNAs (By similarity). While stable tRNAs receive only 3'-terminal CCA,
CC       unstable tRNAs are marked with CCACCA and rapidly degraded (By
CC       similarity). The structural flexibility of RNA controls the choice
CC       between CCA versus CCACCA addition: following the first CCA addition
CC       cycle, nucleotide-binding to the active site triggers a clockwise screw
CC       motion, producing torque on the RNA (By similarity). This ejects stable
CC       RNAs, whereas unstable RNAs are refolded while bound to the enzyme and
CC       subjected to a second CCA catalytic cycle (By similarity).
CC       {ECO:0000250|UniProtKB:Q96Q11, ECO:0000269|PubMed:1634528,
CC       ECO:0000269|PubMed:23872483}.
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:0000269|PubMed:1634528};
CC   -!- INTERACTION:
CC       P21269; P00925: ENO2; NbExp=2; IntAct=EBI-4347, EBI-6475;
CC   -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion
CC       {ECO:0000269|PubMed:1634528, ECO:0000269|PubMed:8175766}.
CC   -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic+nuclear 1]: Cytoplasm
CC       {ECO:0000269|PubMed:1634528, ECO:0000269|PubMed:8175766}. Nucleus
CC       {ECO:0000269|PubMed:8175766}.
CC   -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic+nuclear 2]: Cytoplasm
CC       {ECO:0000269|PubMed:1634528, ECO:0000269|PubMed:8175766}. Nucleus
CC       {ECO:0000269|PubMed:8175766}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=3;
CC       Name=Mitochondrial;
CC         IsoId=P21269-1; Sequence=Displayed;
CC       Name=Cytoplasmic+nuclear 1;
CC         IsoId=P21269-2; Sequence=VSP_018698;
CC       Name=Cytoplasmic+nuclear 2;
CC         IsoId=P21269-3; Sequence=VSP_018699;
CC   -!- MISCELLANEOUS: Present with 13500 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- MISCELLANEOUS: [Isoform Cytoplasmic+nuclear 1]: Produced by alternative
CC       initiation at Met-10 of isoform Mitochondrial. {ECO:0000305}.
CC   -!- MISCELLANEOUS: [Isoform Cytoplasmic+nuclear 2]: Produced by alternative
CC       initiation at Met-18 of isoform Mitochondrial. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the tRNA nucleotidyltransferase/poly(A)
CC       polymerase family. {ECO:0000305}.
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DR   EMBL; M59870; AAA35160.1; -; Genomic_DNA.
DR   EMBL; U18922; AAB64695.1; -; Genomic_DNA.
DR   EMBL; BK006939; DAA07830.1; -; Genomic_DNA.
DR   PIR; S11180; S11180.
DR   RefSeq; NP_011095.1; NM_001179058.1. [P21269-1]
DR   AlphaFoldDB; P21269; -.
DR   SMR; P21269; -.
DR   BioGRID; 36921; 269.
DR   DIP; DIP-2841N; -.
DR   IntAct; P21269; 6.
DR   MINT; P21269; -.
DR   STRING; 4932.YER168C; -.
DR   iPTMnet; P21269; -.
DR   MaxQB; P21269; -.
DR   PaxDb; 4932-YER168C; -.
DR   PeptideAtlas; P21269; -.
DR   EnsemblFungi; YER168C_mRNA; YER168C; YER168C. [P21269-1]
DR   GeneID; 856915; -.
DR   KEGG; sce:YER168C; -.
DR   AGR; SGD:S000000970; -.
DR   SGD; S000000970; CCA1.
DR   VEuPathDB; FungiDB:YER168C; -.
DR   eggNOG; KOG2159; Eukaryota.
DR   GeneTree; ENSGT00390000009678; -.
DR   HOGENOM; CLU_019592_2_1_1; -.
DR   InParanoid; P21269; -.
DR   OMA; WQKFLDH; -.
DR   OrthoDB; 5402987at2759; -.
DR   BioCyc; YEAST:G3O-30329-MONOMER; -.
DR   BRENDA; 2.7.7.72; 984.
DR   BioGRID-ORCS; 856915; 8 hits in 10 CRISPR screens.
DR   PRO; PR:P21269; -.
DR   Proteomes; UP000002311; Chromosome V.
DR   RNAct; P21269; Protein.
DR   GO; GO:0005759; C:mitochondrial matrix; IDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0052929; F:ATP:3'-cytidine-cytidine-tRNA adenylyltransferase activity; IDA:SGD.
DR   GO; GO:0004810; F:CCA tRNA nucleotidyltransferase activity; IDA:SGD.
DR   GO; GO:0052927; F:CTP:tRNA cytidylyltransferase activity; IDA:SGD.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0001680; P:tRNA 3'-terminal CCA addition; IDA:SGD.
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; PTHR13734:SF5; CCA TRNA NUCLEOTIDYLTRANSFERASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR13734; TRNA-NUCLEOTIDYLTRANSFERASE; 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.
PE   1: Evidence at protein level;
KW   Alternative initiation; ATP-binding; Cytoplasm; Direct protein sequencing;
KW   Mitochondrion; Nucleotide-binding; Nucleotidyltransferase; Nucleus;
KW   Reference proteome; RNA-binding; Transferase; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..546
FT                   /note="CCA tRNA nucleotidyltransferase, mitochondrial"
FT                   /id="PRO_0000004779"
FT   VAR_SEQ         1..17
FT                   /note="Missing (in isoform Cytoplasmic+nuclear 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_018699"
FT   VAR_SEQ         1..9
FT                   /note="Missing (in isoform Cytoplasmic+nuclear 1)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_018698"
FT   MUTAGEN         64
FT                   /note="R->N: No effect. Compensates K-189 mutant; when
FT                   associated with K-189."
FT                   /evidence="ECO:0000269|PubMed:23872483"
FT   MUTAGEN         189
FT                   /note="E->K: Temperature-sensitive mutation; reduced
FT                   ability to incorporate AMP and CMP at 37 degrees Celsius.
FT                   Defects are compensated by mutant N-64; when associated
FT                   with N-64."
FT                   /evidence="ECO:0000269|PubMed:23872483"
SQ   SEQUENCE   546 AA;  62485 MW;  C0B2B918596E19D5 CRC64;
     MLRSTISLLM NSAAQKTMTN SNFVLNAPKI TLTKVEQNIC NLLNDYTDLY NQKYHNKPEP
     LTLRITGGWV RDKLLGQGSH DLDIAINVMS GEQFATGLNE YLQQHYAKYG AKPHNIHKID
     KNPEKSKHLE TATTKLFGVE VDFVNLRSEK YTELSRIPKV CFGTPEEDAL RRDATLNALF
     YNIHKGEVED FTKRGLQDLK DGVLRTPLPA KQTFLDDPLR VLRLIRFASR FNFTIDPEVM
     AEMGDPQINV AFNSKISRER VGVEMEKILV GPTPLLALQL IQRAHLENVI FFWHNDSSVV
     KFNEENCQDM DKINHVYNDN ILNSHLKSFI ELYPMFLEKL PILREKIGRS PGFQQNFILS
     AILSPMANLQ IIGNPKKKIN NLVSVTESIV KEGLKLSKND AAVIAKTVDS ICSYEEILAK
     FADRSQLKKS EIGIFLRNFN GEWETAHFAS LSDAFLKIPK LETKKIELLF QNYNEFYSYI
     FDNNLNNCHE LKPIVDGKQM AKLLQMKPGP WLGKINNEAI RWQFDNPTGT DQELITHLKA
     ILPKYL
//