SYK_RAT
ID SYK_RAT Reviewed; 626 AA.
AC Q5XIM7;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Lysine--tRNA ligase {ECO:0000255|RuleBase:RU003748};
DE EC=2.7.7.- {ECO:0000269|PubMed:19524539, ECO:0000269|PubMed:3988754};
DE EC=6.1.1.6 {ECO:0000255|RuleBase:RU003748, ECO:0000269|PubMed:2995387, ECO:0000269|PubMed:6315704};
DE AltName: Full=Lysyl-tRNA synthetase {ECO:0000255|RuleBase:RU003748, ECO:0000303|PubMed:6315704};
DE Short=LysRS;
GN Name=Kars1 {ECO:0000250|UniProtKB:Q15046};
GN Synonyms=Kars {ECO:0000312|RGD:1359653};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|EMBL:AAH83652.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=6315704; DOI=10.1016/s0021-9258(17)43956-1;
RA Hilderman R.H., Zimmerman J.K., Dang C.V., Grothusen J.R.;
RT "Characterization of a homogeneous arginyl- and lysyl-tRNA synthetase
RT complex isolated from rat liver. Kinetic mechanism for lysyl-tRNA
RT synthetase.";
RL J. Biol. Chem. 258:13592-13596(1983).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=3988754; DOI=10.1016/s0021-9258(18)89019-6;
RA Wahab S.Z., Yang D.C.;
RT "Synthesis of diadenosine 5',5''' -P1,P4-tetraphosphate by lysyl-tRNA
RT synthetase and a multienzyme complex of aminoacyl-tRNA synthetases from rat
RT liver.";
RL J. Biol. Chem. 260:5286-5289(1985).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=2995387; DOI=10.1016/s0021-9258(17)38937-8;
RA Wahab S.Z., Yang D.C.;
RT "Influence of supramolecular structure on the enzyme mechanisms of rat
RT liver lysyl-tRNA synthetase-catalyzed reactions. Synthesis of P1,P4-bis(5'-
RT adenosyl)tetraphosphate.";
RL J. Biol. Chem. 260:12735-12739(1985).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, PHOSPHORYLATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19524539; DOI=10.1016/j.molcel.2009.05.019;
RA Yannay-Cohen N., Carmi-Levy I., Kay G., Yang C.M., Han J.M., Kemeny D.M.,
RA Kim S., Nechushtan H., Razin E.;
RT "LysRS serves as a key signaling molecule in the immune response by
RT regulating gene expression.";
RL Mol. Cell 34:603-611(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-623 AND SER-625, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MITF.
RX PubMed=23159739; DOI=10.1016/j.molcel.2012.10.010;
RA Ofir-Birin Y., Fang P., Bennett S.P., Zhang H.M., Wang J., Rachmin I.,
RA Shapiro R., Song J., Dagan A., Pozo J., Kim S., Marshall A.G., Schimmel P.,
RA Yang X.L., Nechushtan H., Razin E., Guo M.;
RT "Structural switch of lysyl-tRNA synthetase between translation and
RT transcription.";
RL Mol. Cell 49:30-42(2013).
CC -!- FUNCTION: Catalyzes the specific attachment of an amino acid to its
CC cognate tRNA in a 2 step reaction: the amino acid (AA) is first
CC activated by ATP to form AA-AMP and then transferred to the acceptor
CC end of the tRNA (PubMed:6315704). When secreted, acts as a signaling
CC molecule that induces immune response through the activation of
CC monocyte/macrophages (By similarity). Catalyzes the synthesis of the
CC signaling molecule diadenosine tetraphosphate (Ap4A), and thereby
CC mediates disruption of the complex between HINT1 and MITF and the
CC concomitant activation of MITF transcriptional activity
CC (PubMed:3988754, PubMed:2995387, PubMed:19524539).
CC {ECO:0000250|UniProtKB:Q15046, ECO:0000269|PubMed:19524539,
CC ECO:0000269|PubMed:2995387, ECO:0000269|PubMed:3988754,
CC ECO:0000269|PubMed:6315704}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-lysine + tRNA(Lys) = AMP + diphosphate + L-lysyl-
CC tRNA(Lys); Xref=Rhea:RHEA:20792, Rhea:RHEA-COMP:9696, Rhea:RHEA-
CC COMP:9697, ChEBI:CHEBI:30616, ChEBI:CHEBI:32551, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78529, ChEBI:CHEBI:456215; EC=6.1.1.6;
CC Evidence={ECO:0000269|PubMed:6315704};
CC -!- SUBUNIT: Homodimer (By similarity). Part of the multisynthetase complex
CC (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS),
CC Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS)
CC the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary
CC subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:3988754,
CC PubMed:2995387, PubMed:19524539). Interacts with AIMP2 (via N-terminus)
CC and MITF (PubMed:23159739). Interacts with TARSL2 (By similarity).
CC {ECO:0000250|UniProtKB:Q15046, ECO:0000269|PubMed:23159739,
CC ECO:0000305|PubMed:19524539, ECO:0000305|PubMed:2995387,
CC ECO:0000305|PubMed:3988754}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:19524539,
CC ECO:0000269|PubMed:23159739}. Cytoplasm {ECO:0000250|UniProtKB:Q15046}.
CC Nucleus {ECO:0000269|PubMed:19524539, ECO:0000269|PubMed:23159739}.
CC Cell membrane {ECO:0000250|UniProtKB:Q15046}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q15046}. Secreted
CC {ECO:0000250|UniProtKB:Q15046}. Note=Secretion is induced by TNF-alpha
CC (By similarity). Cytosolic in quiescent mast cells. Translocates into
CC the nucleus in response to mast cell activation by immunoglobulin E
CC (PubMed:19524539, PubMed:23159739). {ECO:0000250|UniProtKB:Q15046,
CC ECO:0000269|PubMed:19524539, ECO:0000269|PubMed:23159739}.
CC -!- DOMAIN: The N-terminal domain (1-65) is a functional tRNA-binding
CC domain and is involved in the interaction with DARS, but has a
CC repulsive role in the binding to EEF1A1. A central domain (208-259) is
CC involved in homodimerization. The C-terminal domain (452-597) is not
CC required for interaction with AIMP2 (By similarity).
CC {ECO:0000250|UniProtKB:Q15046}.
CC -!- PTM: Phosphorylated on a serine residue after mast cell stimulation
CC with immunoglobulin E (IgE). {ECO:0000269|PubMed:19524539}.
CC -!- MISCELLANEOUS: It is likely that the same gene provides both this
CC cytoplasmic isoform and an additional mitochondrial isoform.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC {ECO:0000305}.
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DR EMBL; AC117869; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC083652; AAH83652.1; -; mRNA.
DR EMBL; CH473972; EDL92602.1; -; Genomic_DNA.
DR RefSeq; NP_001006968.1; NM_001006967.1.
DR AlphaFoldDB; Q5XIM7; -.
DR SMR; Q5XIM7; -.
DR CORUM; Q5XIM7; -.
DR STRING; 10116.ENSRNOP00000044454; -.
DR MoonProt; Q5XIM7; -.
DR iPTMnet; Q5XIM7; -.
DR PhosphoSitePlus; Q5XIM7; -.
DR jPOST; Q5XIM7; -.
DR PaxDb; Q5XIM7; -.
DR PRIDE; Q5XIM7; -.
DR Ensembl; ENSRNOT00000046126; ENSRNOP00000044454; ENSRNOG00000019456.
DR GeneID; 292028; -.
DR KEGG; rno:292028; -.
DR UCSC; RGD:1359653; rat.
DR CTD; 3735; -.
DR RGD; 1359653; Kars.
DR eggNOG; KOG1885; Eukaryota.
DR GeneTree; ENSGT01030000234618; -.
DR HOGENOM; CLU_008255_6_0_1; -.
DR InParanoid; Q5XIM7; -.
DR OMA; EIFGEKC; -.
DR OrthoDB; 837479at2759; -.
DR PhylomeDB; Q5XIM7; -.
DR TreeFam; TF300365; -.
DR PRO; PR:Q5XIM7; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Proteomes; UP000234681; Chromosome 19.
DR Bgee; ENSRNOG00000019456; Expressed in skeletal muscle tissue and 20 other tissues.
DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:CAFA.
DR GO; GO:0005737; C:cytoplasm; IDA:CAFA.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:CAFA.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016597; F:amino acid binding; IDA:RGD.
DR GO; GO:0003877; F:ATP adenylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004824; F:lysine-tRNA ligase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0000049; F:tRNA binding; IDA:RGD.
DR GO; GO:0002276; P:basophil activation involved in immune response; IMP:CAFA.
DR GO; GO:0015966; P:diadenosine tetraphosphate biosynthetic process; IDA:RGD.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IMP:CAFA.
DR GO; GO:0006430; P:lysyl-tRNA aminoacylation; IDA:UniProtKB.
DR GO; GO:0002863; P:positive regulation of inflammatory response to antigenic stimulus; ISO:RGD.
DR GO; GO:0043032; P:positive regulation of macrophage activation; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:CAFA.
DR GO; GO:0010165; P:response to X-ray; IDA:RGD.
DR CDD; cd00775; LysRS_core; 1.
DR CDD; cd04322; LysRS_N; 1.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR HAMAP; MF_00252; Lys_tRNA_synth_class2; 1.
DR InterPro; IPR004364; Aa-tRNA-synt_II.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR002313; Lys-tRNA-ligase_II.
DR InterPro; IPR034762; Lys-tRNA-ligase_II_bac/euk.
DR InterPro; IPR044136; Lys-tRNA-ligase_II_N.
DR InterPro; IPR018149; Lys-tRNA-synth_II_C.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR004365; NA-bd_OB_tRNA.
DR Pfam; PF00152; tRNA-synt_2; 1.
DR Pfam; PF01336; tRNA_anti-codon; 1.
DR PIRSF; PIRSF039101; LysRS2; 1.
DR PRINTS; PR00982; TRNASYNTHLYS.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00499; lysS_bact; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
PE 1: Evidence at protein level;
KW Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Cell membrane;
KW Cytoplasm; Ligase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Protein biosynthesis; Reference proteome; Secreted; Transferase.
FT CHAIN 1..626
FT /note="Lysine--tRNA ligase"
FT /id="PRO_0000441253"
FT REGION 604..626
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 306
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 330
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 352..354
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 360..361
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 368
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 370
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 523..524
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 526
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 530
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 579..582
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 117
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 170
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 236
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MN1"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MN1"
FT MOD_RES 620
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99MN1"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 625
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 626 AA; 71623 MW; 4FE3972CBC054F82 CRC64;
MLMQAAVRLV RGSLRQTSWA EWGQRELRLG QLAPFTTLRK DKPLSDRRSE LKRRLKAEKK
LAEKEAKQKE LSEKQLNQTT AAAATNHTAD NGVGAEEETL DPNQYYKIRS QAVQQLKVSG
EDPYPHKFHV DISLTQFIQE YSHLQPGDHL TDITLKVAGR IHAKRASGGK LIFYDLRGEG
VKLQVMANSR NYKSEEEFVH INNKLRRGDI IGVEGNPGKT KKGELSIVPR EMTLLSPCLH
MLPHLHFGLK DKETRYRQRY LDLILNDFVR QKFIIRSKII TYIRSFLDEL GFLEIETPMM
NIIPGGAVAK PFITYHNELD MNLYMRIAPE LYHKMLVVGG IDRVYEIGRQ FRNEGIDLTH
NPEFTTCEFY MAYADYHDLM EITEKMLSGM VRSITGSYKI TYHPDGPEGQ AYEIDFTPPF
RRISMVEELE KVLGVKLPET SLFETEETRK ILDDICVARA VECPPPRTTA RLLDKLVGEF
LEVTCISPTF ICDHPQIMSP LAKWHRCKEG LTERFELFVM KKEICNAYTE LNDPVRQRQL
FEEQAKAKAA GDDEAMFIDE NFCTALEYGL PPTAGWGMGI DRVTMFLTDS NNIKEVLLFP
AMKPEDKKET ATATETPEST EASPSV
