SYTC2_HUMAN
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 03-AUG-2022, entry version 133.
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};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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; 59.
DR IntAct; A2RTX5; 36.
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; A2RTX5; -.
DR PeptideAtlas; A2RTX5; -.
DR PRIDE; A2RTX5; -.
DR ProteomicsDB; 483; -. [A2RTX5-1]
DR ProteomicsDB; 484; -. [A2RTX5-2]
DR Antibodypedia; 53619; 141 antibodies from 20 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 CTD; 123283; -.
DR DisGeNET; 123283; -.
DR GeneCards; TARS3; -.
DR HGNC; HGNC:24728; TARS3.
DR HPA; ENSG00000185418; Tissue enhanced (brain, 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; IWDEAEK; -.
DR OrthoDB; 813937at2759; -.
DR PhylomeDB; A2RTX5; -.
DR TreeFam; TF300858; -.
DR PathwayCommons; A2RTX5; -.
DR SignaLink; A2RTX5; -.
DR BioGRID-ORCS; 123283; 9 hits in 1080 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 173 other tissues.
DR ExpressionAtlas; A2RTX5; baseline and differential.
DR Genevisible; A2RTX5; HS.
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; cd00771; ThrRS_core; 1.
DR Gene3D; 3.10.20.30; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR Gene3D; 3.40.50.800; -; 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; IPR033728; ThrRS_core.
DR InterPro; IPR012947; tRNA_SAD.
DR PANTHER; PTHR11451; PTHR11451; 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; SSF55186; SSF55186; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR SUPFAM; SSF81271; SSF81271; 1.
DR TIGRFAMs; TIGR00418; thrS; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
DR PROSITE; PS51880; TGS; 1.
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
