SYK_CRIGR
ID SYK_CRIGR Reviewed; 597 AA.
AC P37879;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Lysine--tRNA ligase;
DE EC=2.7.7.- {ECO:0000250|UniProtKB:Q15046};
DE EC=6.1.1.6 {ECO:0000269|PubMed:11706011};
DE AltName: Full=Lysyl-tRNA synthetase;
DE Short=LysRS;
GN Name=KARS1 {ECO:0000250|UniProtKB:Q15046}; Synonyms=KARS;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=8952483; DOI=10.1021/bi9617926;
RA Agou F., Quevillon S., Kerjan P., Latreille M.-T., Mirande M.;
RT "Functional replacement of hamster lysyl-tRNA synthetase by the yeast
RT enzyme requires cognate amino acid sequences for proper tRNA recognition.";
RL Biochemistry 35:15322-15331(1996).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF 1-MET--GLN-50.
RX PubMed=11706011; DOI=10.1074/jbc.m109759200;
RA Francin M., Kaminska M., Kerjan P., Mirande M.;
RT "The N-terminal domain of mammalian Lysyl-tRNA synthetase is a functional
RT tRNA-binding domain.";
RL J. Biol. Chem. 277:1762-1769(2002).
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:11706011). When secreted, acts as a signaling
CC molecule that induces immune response through the activation of
CC monocyte/macrophages. Catalyzes the synthesis of the signaling molecule
CC diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of
CC the complex between HINT1 and MITF and the concomitant activation of
CC MITF transcriptional activity (By similarity).
CC {ECO:0000250|UniProtKB:Q15046, ECO:0000269|PubMed:11706011}.
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:11706011};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=104 uM for lysine {ECO:0000269|PubMed:11706011};
CC KM=250 uM for ATP {ECO:0000269|PubMed:11706011};
CC KM=3.0 uM for tRNA(3)Lys {ECO:0000269|PubMed:11706011};
CC -!- SUBUNIT: Homodimer. Part of the multisynthetase complex (MSC), a
CC multisubunit complex that groups tRNA ligases for Arg (RARS), Asp
CC (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the
CC bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits
CC AIMP1/p43, AIMP2/p38 and EEF1E1/p18. Interacts with AIMP2 (via N-
CC terminus) and MITF. Interacts with TARSL2.
CC {ECO:0000250|UniProtKB:Q15046}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q15046}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q15046}. Nucleus {ECO:0000250|UniProtKB:Q15046}.
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 Cytosolic in quiescent mast cells. Translocates into the nucleus in
CC response to mast cell activation by immunoglobulin E.
CC {ECO:0000250|UniProtKB:Q15046}.
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:0000250|UniProtKB:Q5XIM7}.
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; Z31711; CAA83505.1; -; mRNA.
DR PIR; S43187; S43187.
DR RefSeq; XP_003510206.1; XM_003510158.3.
DR AlphaFoldDB; P37879; -.
DR SMR; P37879; -.
DR IntAct; P37879; 1.
DR STRING; 10029.XP_007627885.1; -.
DR Ensembl; ENSCGRT00001004876; ENSCGRP00001003392; ENSCGRG00001004055.
DR GeneID; 100766627; -.
DR KEGG; cge:100766627; -.
DR CTD; 3735; -.
DR eggNOG; KOG1885; Eukaryota.
DR GeneTree; ENSGT01030000234618; -.
DR OMA; EIFGEKC; -.
DR SABIO-RK; P37879; -.
DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003877; F:ATP adenylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004824; F:lysine-tRNA ligase activity; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0015966; P:diadenosine tetraphosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006430; P:lysyl-tRNA aminoacylation; IDA:UniProtKB.
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; Secreted; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT CHAIN 2..597
FT /note="Lysine--tRNA ligase"
FT /id="PRO_0000152764"
FT BINDING 277
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 301
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 323..325
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 331..332
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 339
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 341
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 494..495
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 497
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 501
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 550..553
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 88
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 141
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 207
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MN1"
FT MOD_RES 590
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MN1"
FT MOD_RES 591
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99MN1"
FT MOD_RES 596
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99MN1"
FT MUTAGEN 2..50
FT /note="Missing: 100-fold lower apparent affinity for
FT tRNA(3)Lys."
SQ SEQUENCE 597 AA; 67990 MW; 23DBA6845CD87D0D CRC64;
MATLQECKVK VDGEPKLSKN ELKRRLKAEK KLAEKEAKQK ELIEKQLSQA AAAAATNHTA
DNGVGVEEET LDPNQYYKIR SQAIHQLKVS GEDPYPHKFH VDISLTQFIQ EYSQLQPGDH
LTDITLKVAG RIHAKRASGG KLIFYDLRGE GVKLQVMANS RNYKSEEEFV RINNKLRRGD
IIGVQGNPGK TKKGELSIIP YEITLLSPCL HMLPHLHFGL KDKETRYRQR YLDLILNDFV
RQKFIVRAKI ITYIRSFLDE LGFLEIETPM MNIIPGGAVA KPFITYHNEL DMNLYMRIAP
ELYHKMLVVG GIDRVYEIGR QFRNEGIDLT HNPEFTTCEF YMAYADYHDL MEITEKMLSG
MVKSITGSYK ITYHPDGPEG EAYEIDFTPP FRRISMVEEL EKALGVKLPE TSLFETEETR
KILDDICVAK AVECPPPRTT ARLLDKLVGE FLEVTCINPT FICDHPQIMS PLAKWHRSKE
GLTERFELFV MKKEICNAYT ELNDPMRQRQ LFEEQAKAKA AGDDEAMFID ENFCTALEYG
LPPTAGWGMG IDRVTMFLTD SNNIKEVLLF PAMKPEDKKE TAAATETLES TTAGPSV
