ID   SYTC2_HUMAN             Reviewed;         802 AA.
AC   A2RTX5; B2RMP7; Q6B0A1; Q6IS76; Q96LW3; Q96MP4;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2007, sequence version 1.
DT   24-JAN-2024, entry version 140.
DE   RecName: Full=Threonine--tRNA ligase 2, cytoplasmic {ECO:0000305};
DE            EC=6.1.1.3 {ECO:0000250|UniProtKB:Q8BLY2};
DE   AltName: Full=Threonyl-tRNA synthetase;
DE            Short=ThrRS;
DE   AltName: Full=Threonyl-tRNA synthetase protein 3;
GN   Name=TARS3 {ECO:0000312|HGNC:HGNC:24728}; Synonyms=TARSL2;
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] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 315-802 (ISOFORM 1).
RC   TISSUE=Cerebellum;
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 337-802 (ISOFORMS 1/2).
RC   TISSUE=Brain, and Lung;
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].
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   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-453, 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   PROTEIN SEQUENCE OF 114-126; 154-201; 271-287; 322-333; 358-386; 427-441;
RP   446-461; 512-534; 596-623; 678-691 AND 698-712, IDENTIFICATION IN THE MSC
RP   COMPLEX, INTERACTION WITH EPRS1; AIMP1; AIMP2 AND KARS1, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY.
RX   PubMed=24312579; DOI=10.1371/journal.pone.0081734;
RA   Kim K., Park S.J., Na S., Kim J.S., Choi H., Kim Y.K., Paek E., Lee C.;
RT   "Reinvestigation of aminoacyl-tRNA synthetase core complex by affinity
RT   purification-mass spectrometry reveals TARSL2 as a potential member of the
RT   complex.";
RL   PLoS ONE 8:E81734-E81734(2013).
CC   -!- FUNCTION: Catalyzes the attachment of threonine to tRNA(Thr) in a two-
CC       step reaction: threonine is first activated by ATP to form Thr-AMP and
CC       then transferred to the acceptor end of tRNA(Thr). Also edits
CC       incorrectly charged tRNA(Thr) via its editing domain, at the post-
CC       transfer stage. {ECO:0000250|UniProtKB:Q8BLY2}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonine + tRNA(Thr) = AMP + diphosphate + H(+) + L-
CC         threonyl-tRNA(Thr); Xref=Rhea:RHEA:24624, Rhea:RHEA-COMP:9670,
CC         Rhea:RHEA-COMP:9704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:57926, ChEBI:CHEBI:78442,
CC         ChEBI:CHEBI:78534, ChEBI:CHEBI:456215; EC=6.1.1.3;
CC         Evidence={ECO:0000250|UniProtKB:Q8BLY2};
CC   -!- SUBUNIT: May be a component of the multisynthetase complex (MSC), a
CC       large multi-subunit complex which contains at least eight different
CC       aminoacyl-tRNA synthetases plus three auxillary subunits AIMP1, AIMP2
CC       and EEF1E1. Interacts with the MSC components EPRS1, AIMP1, AIMP2 and
CC       KARS1. {ECO:0000269|PubMed:24312579}.
CC   -!- INTERACTION:
CC       A2RTX5; O15145: ARPC3; NbExp=3; IntAct=EBI-1056629, EBI-351829;
CC       A2RTX5; P18848: ATF4; NbExp=3; IntAct=EBI-1056629, EBI-492498;
CC       A2RTX5; Q9BQ95: ECSIT; NbExp=3; IntAct=EBI-1056629, EBI-712452;
CC       A2RTX5; Q8TCE9: LGALS14; NbExp=3; IntAct=EBI-1056629, EBI-10274069;
CC       A2RTX5; P26639: TARS1; NbExp=6; IntAct=EBI-1056629, EBI-1042683;
CC       A2RTX5; Q9BW92: TARS2; NbExp=3; IntAct=EBI-1056629, EBI-1045099;
CC       A2RTX5; Q05BL1: TP53BP2; NbExp=3; IntAct=EBI-1056629, EBI-11952721;
CC       A2RTX5; B2RDX5; NbExp=3; IntAct=EBI-1056629, EBI-10173104;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BLY2}. Nucleus
CC       {ECO:0000250|UniProtKB:Q8BLY2}. Note=Primarily cytoplasmic. Also
CC       detected at lower levels in the nucleus.
CC       {ECO:0000250|UniProtKB:Q8BLY2}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=A2RTX5-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=A2RTX5-2; Sequence=VSP_033562;
CC   -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAB71554.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AK056653; BAB71241.1; -; mRNA.
DR   EMBL; AK057734; BAB71554.1; ALT_INIT; mRNA.
DR   EMBL; CH471101; EAX02316.1; -; Genomic_DNA.
DR   EMBL; BC069346; AAH69346.1; -; mRNA.
DR   EMBL; BC069811; AAH69811.1; -; mRNA.
DR   EMBL; BC074887; AAH74887.1; -; mRNA.
DR   EMBL; BC132671; AAI32672.1; -; mRNA.
DR   EMBL; BC136315; AAI36316.1; -; mRNA.
DR   CCDS; CCDS10394.1; -. [A2RTX5-1]
DR   RefSeq; NP_689547.2; NM_152334.2. [A2RTX5-1]
DR   AlphaFoldDB; A2RTX5; -.
DR   SMR; A2RTX5; -.
DR   BioGRID; 125822; 63.
DR   IntAct; A2RTX5; 37.
DR   MINT; A2RTX5; -.
DR   STRING; 9606.ENSP00000338093; -.
DR   GlyGen; A2RTX5; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; A2RTX5; -.
DR   PhosphoSitePlus; A2RTX5; -.
DR   BioMuta; TARSL2; -.
DR   EPD; A2RTX5; -.
DR   jPOST; A2RTX5; -.
DR   MassIVE; A2RTX5; -.
DR   MaxQB; A2RTX5; -.
DR   PaxDb; 9606-ENSP00000338093; -.
DR   PeptideAtlas; A2RTX5; -.
DR   ProteomicsDB; 483; -. [A2RTX5-1]
DR   ProteomicsDB; 484; -. [A2RTX5-2]
DR   Pumba; A2RTX5; -.
DR   Antibodypedia; 53619; 151 antibodies from 21 providers.
DR   DNASU; 123283; -.
DR   Ensembl; ENST00000335968.8; ENSP00000338093.3; ENSG00000185418.16. [A2RTX5-1]
DR   GeneID; 123283; -.
DR   KEGG; hsa:123283; -.
DR   MANE-Select; ENST00000335968.8; ENSP00000338093.3; NM_152334.3; NP_689547.2.
DR   UCSC; uc002bxm.4; human. [A2RTX5-1]
DR   AGR; HGNC:24728; -.
DR   CTD; 123283; -.
DR   DisGeNET; 123283; -.
DR   GeneCards; TARS3; -.
DR   HGNC; HGNC:24728; TARS3.
DR   HPA; ENSG00000185418; Tissue enhanced (skeletal muscle, tongue).
DR   neXtProt; NX_A2RTX5; -.
DR   OpenTargets; ENSG00000185418; -.
DR   PharmGKB; PA128394753; -.
DR   VEuPathDB; HostDB:ENSG00000185418; -.
DR   eggNOG; KOG1637; Eukaryota.
DR   GeneTree; ENSGT00940000159348; -.
DR   InParanoid; A2RTX5; -.
DR   OMA; TPMDIAG; -.
DR   OrthoDB; 1119631at2759; -.
DR   PhylomeDB; A2RTX5; -.
DR   TreeFam; TF300858; -.
DR   PathwayCommons; A2RTX5; -.
DR   SignaLink; A2RTX5; -.
DR   BioGRID-ORCS; 123283; 9 hits in 1154 CRISPR screens.
DR   ChiTaRS; TARSL2; human.
DR   GenomeRNAi; 123283; -.
DR   Pharos; A2RTX5; Tbio.
DR   PRO; PR:A2RTX5; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; A2RTX5; Protein.
DR   Bgee; ENSG00000185418; Expressed in corpus callosum and 175 other cell types or tissues.
DR   ExpressionAtlas; A2RTX5; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; IEA:UniProt.
DR   GO; GO:0004829; F:threonine-tRNA ligase activity; ISS:UniProtKB.
DR   GO; GO:0006435; P:threonyl-tRNA aminoacylation; ISS:UniProtKB.
DR   CDD; cd01667; TGS_ThrRS; 1.
DR   CDD; cd00860; ThrRS_anticodon; 1.
DR   CDD; cd00771; ThrRS_core; 1.
DR   Gene3D; 3.10.20.30; -; 1.
DR   Gene3D; 3.40.50.800; Anticodon-binding domain; 1.
DR   HAMAP; MF_00184; Thr_tRNA_synth; 1.
DR   InterPro; IPR002314; aa-tRNA-synt_IIb.
DR   InterPro; IPR006195; aa-tRNA-synth_II.
DR   InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR   InterPro; IPR004154; Anticodon-bd.
DR   InterPro; IPR036621; Anticodon-bd_dom_sf.
DR   InterPro; IPR012675; Beta-grasp_dom_sf.
DR   InterPro; IPR004095; TGS.
DR   InterPro; IPR012676; TGS-like.
DR   InterPro; IPR002320; Thr-tRNA-ligase_IIa.
DR   InterPro; IPR018163; Thr/Ala-tRNA-synth_IIc_edit.
DR   InterPro; IPR047246; ThrRS_anticodon.
DR   InterPro; IPR033728; ThrRS_core.
DR   InterPro; IPR012947; tRNA_SAD.
DR   NCBIfam; TIGR00418; thrS; 1.
DR   PANTHER; PTHR11451:SF38; THREONINE--TRNA LIGASE 2, CYTOPLASMIC; 1.
DR   PANTHER; PTHR11451; THREONINE-TRNA LIGASE; 1.
DR   Pfam; PF03129; HGTP_anticodon; 1.
DR   Pfam; PF02824; TGS; 1.
DR   Pfam; PF00587; tRNA-synt_2b; 1.
DR   Pfam; PF07973; tRNA_SAD; 1.
DR   PRINTS; PR01047; TRNASYNTHTHR.
DR   SMART; SM00863; tRNA_SAD; 1.
DR   SUPFAM; SSF52954; Class II aaRS ABD-related; 1.
DR   SUPFAM; SSF55681; Class II aaRS and biotin synthetases; 1.
DR   SUPFAM; SSF81271; TGS-like; 1.
DR   SUPFAM; SSF55186; ThrRS/AlaRS common domain; 1.
DR   PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
DR   PROSITE; PS51880; TGS; 1.
DR   Genevisible; A2RTX5; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding;
KW   Coiled coil; Cytoplasm; Direct protein sequencing; Ligase;
KW   Nucleotide-binding; Nucleus; Phosphoprotein; Protein biosynthesis;
KW   Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   CHAIN           2..802
FT                   /note="Threonine--tRNA ligase 2, cytoplasmic"
FT                   /id="PRO_0000333828"
FT   DOMAIN          157..222
FT                   /note="TGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01228"
FT   REGION          86..123
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          3..23
FT                   /evidence="ECO:0000255"
FT   COILED          76..96
FT                   /evidence="ECO:0000255"
FT   MOTIF           786..792
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BLY2"
FT   COMPBIAS        106..123
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0007744|PubMed:22814378"
FT   MOD_RES         453
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         225..319
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_033562"
FT   CONFLICT        96
FT                   /note="A -> G (in Ref. 1; BAB71241)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        166
FT                   /note="V -> A (in Ref. 1; BAB71241)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        210
FT                   /note="R -> C (in Ref. 1; BAB71241)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        337
FT                   /note="I -> N (in Ref. 3; AAH69346/AAH69811)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        513
FT                   /note="F -> C (in Ref. 1; BAB71554)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        533
FT                   /note="R -> G (in Ref. 1; BAB71554)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   802 AA;  92646 MW;  EE83EB934B503E59 CRC64;
     MAAEALAAEA VASRLERQEE DIRWLWSEVE RLRDEQLNAP YSCQAEGPCL TREVAQLRAE
     NCDLRHRLCS LRLCLAEERS RQATLESAEL EAAQEAGAQP PPSQSQDKDM KKKKMKESEA
     DSEVKHQPIF IKERLKLFEI LKKDHQLLLA IYGKKGDTSN IITVRVADGQ TVQGEVWKTT
     PYQVAAEISQ ELAESTVIAK VNGELWDLDR PLEGDSSLEL LTFDNEEAQA VYWHSSAHIL
     GEAMELYYGG HLCYGPPIEN GFYYDMFIED RAVSSTELSA LENICKAIIK EKQPFERLEV
     SKEILLEMFK YNKFKCRILN EKVNTATTTV YRCGPLIDLC KGPHVRHTGK IKTIKIFKNS
     STYWEGNPEM ETLQRIYGIS FPDNKMMRDW EKFQEEAKNR DHRKIGKEQE LFFFHDLSPG
     SCFFLPRGAF IYNTLTDFIR EEYHKRDFTE VLSPNMYNSK LWEASGHWQH YSENMFTFEI
     EKDTFALKPM NCPGHCLMFA HRPRSWREMP IRFADFGVLH RNELSGTLSG LTRVRRFQQD
     DAHIFCTVEQ IEEEIKGCLQ FLQSVYSTFG FSFQLNLSTR PENFLGEIEM WNEAEKQLQN
     SLMDFGEPWK MNPGDGAFYG PKIDIKIKDA IGRYHQCATI QLDFQLPIRF NLTYVSKDGD
     DKKRPVIIHR AILGSVERMI AILSENYGGK WPFWLSPRQV MVIPVGPTCE KYALQVSSEF
     FEEGFMADVD LDHSCTLNKK IRNAQLAQYN FILVVGEKEK IDNAVNVRTR DNKIHGEILV
     TSAIDKLKNL RKTRTLNAEE AF
//