SYK_MOUSE
ID SYK_MOUSE Reviewed; 595 AA.
AC Q99MN1;
DT 16-APR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Lysine--tRNA ligase;
DE EC=2.7.7.- {ECO:0000250|UniProtKB:Q15046};
DE EC=6.1.1.6 {ECO:0000250|UniProtKB:Q15046};
DE AltName: Full=Lysyl-tRNA synthetase;
DE Short=LysRS;
GN Name=Kars1 {ECO:0000250|UniProtKB:Q15046};
GN Synonyms=Kars {ECO:0000312|MGI:MGI:1934754};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=11331948; DOI=10.1007/s003350020008;
RA Maas S., Kim Y.G., Rich A.;
RT "Genomic clustering of tRNA-specific adenosine deaminase ADAT1 and two tRNA
RT synthetases.";
RL Mamm. Genome 12:387-393(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [3]
RP BIDIRECTIONAL PROMOTER WITH TERF2IP.
RX PubMed=14659874; DOI=10.1016/j.gene.2003.08.026;
RA Tan M., Wei C., Price C.M.;
RT "The telomeric protein Rap1 is conserved in vertebrates and is expressed
RT from a bidirectional promoter positioned between the Rap1 and KARS genes.";
RL Gene 323:1-10(2003).
RN [4]
RP SUBUNIT.
RX PubMed=12060739; DOI=10.1073/pnas.122110199;
RA Kim J.Y., Kang Y.-S., Lee J.-W., Kim H.J., Ahn Y.H., Park H., Ko Y.-G.,
RA Kim S.;
RT "p38 is essential for the assembly and stability of macromolecular tRNA
RT synthetase complex: implications for its physiological significance.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:7912-7916(2002).
RN [5]
RP INTERACTION WITH MIFT.
RX PubMed=14975237; DOI=10.1016/s1074-7613(04)00020-2;
RA Lee Y.N., Nechushtan H., Figov N., Razin E.;
RT "The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of
RT MITF activity in FcepsilonRI-activated mast cells.";
RL Immunity 20:145-151(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393; SER-588; THR-589;
RP SER-592 AND SER-594, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. When secreted, acts as a signaling molecule that
CC induces immune response through the activation of monocyte/macrophages.
CC Catalyzes the synthesis of the signaling molecule diadenosine
CC tetraphosphate (Ap4A), and thereby mediates disruption of the complex
CC between HINT1 and MITF and the concomitant activation of MITF
CC transcriptional activity. {ECO:0000250|UniProtKB:Q15046}.
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:0000250|UniProtKB:Q15046};
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:14975237).
CC Interacts with AIMP2 (via N-terminus) and MITF (PubMed:14975237).
CC Interacts with TARSL2 (By similarity). {ECO:0000250|UniProtKB:Q15046,
CC ECO:0000269|PubMed:14975237}.
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 -!- MISCELLANEOUS: Shares a bidirectional promoter with Terf2ip/Rap1.
CC {ECO:0000305|PubMed:14659874}.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC {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; AF328904; AAK19309.1; -; Genomic_DNA.
DR EMBL; AF328894; AAK19309.1; JOINED; Genomic_DNA.
DR EMBL; AF328895; AAK19309.1; JOINED; Genomic_DNA.
DR EMBL; AF328896; AAK19309.1; JOINED; Genomic_DNA.
DR EMBL; AF328897; AAK19309.1; JOINED; Genomic_DNA.
DR EMBL; AF328898; AAK19309.1; JOINED; Genomic_DNA.
DR EMBL; AF328899; AAK19309.1; JOINED; Genomic_DNA.
DR EMBL; AF328900; AAK19309.1; JOINED; Genomic_DNA.
DR EMBL; AF328901; AAK19309.1; JOINED; Genomic_DNA.
DR EMBL; AF328902; AAK19309.1; JOINED; Genomic_DNA.
DR EMBL; AF328903; AAK19309.1; JOINED; Genomic_DNA.
DR EMBL; BC036289; AAH36289.1; -; mRNA.
DR CCDS; CCDS40481.1; -.
DR RefSeq; NP_444322.1; NM_053092.3.
DR AlphaFoldDB; Q99MN1; -.
DR SMR; Q99MN1; -.
DR BioGRID; 220220; 30.
DR DIP; DIP-36058N; -.
DR IntAct; Q99MN1; 3.
DR STRING; 10090.ENSMUSP00000126268; -.
DR iPTMnet; Q99MN1; -.
DR PhosphoSitePlus; Q99MN1; -.
DR EPD; Q99MN1; -.
DR jPOST; Q99MN1; -.
DR MaxQB; Q99MN1; -.
DR PaxDb; Q99MN1; -.
DR PRIDE; Q99MN1; -.
DR ProteomicsDB; 253438; -.
DR Antibodypedia; 16841; 241 antibodies from 36 providers.
DR DNASU; 85305; -.
DR Ensembl; ENSMUST00000034426; ENSMUSP00000034426; ENSMUSG00000031948.
DR GeneID; 85305; -.
DR KEGG; mmu:85305; -.
DR UCSC; uc009nne.3; mouse.
DR CTD; 85305; -.
DR MGI; MGI:1934754; Kars.
DR VEuPathDB; HostDB:ENSMUSG00000031948; -.
DR eggNOG; KOG1885; Eukaryota.
DR GeneTree; ENSGT01030000234618; -.
DR HOGENOM; CLU_008255_6_0_1; -.
DR InParanoid; Q99MN1; -.
DR OMA; EIFGEKC; -.
DR PhylomeDB; Q99MN1; -.
DR BRENDA; 6.1.1.6; 3474.
DR BioGRID-ORCS; 85305; 28 hits in 75 CRISPR screens.
DR ChiTaRS; Kars; mouse.
DR PRO; PR:Q99MN1; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q99MN1; protein.
DR Bgee; ENSMUSG00000031948; Expressed in primitive streak and 271 other tissues.
DR ExpressionAtlas; Q99MN1; baseline and differential.
DR Genevisible; Q99MN1; MM.
DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:CAFA.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0016597; F:amino acid binding; ISO:MGI.
DR GO; GO:0003877; F:ATP adenylyltransferase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004824; F:lysine-tRNA ligase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0097110; F:scaffold protein binding; IPI:CAFA.
DR GO; GO:0000049; F:tRNA binding; ISO:MGI.
DR GO; GO:0002276; P:basophil activation involved in immune response; ISO:MGI.
DR GO; GO:0015966; P:diadenosine tetraphosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0006430; P:lysyl-tRNA aminoacylation; ISS:UniProtKB.
DR GO; GO:0002863; P:positive regulation of inflammatory response to antigenic stimulus; ISO:MGI.
DR GO; GO:0043032; P:positive regulation of macrophage activation; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0010165; P:response to X-ray; ISO:MGI.
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 INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT CHAIN 2..595
FT /note="Lysine--tRNA ligase"
FT /id="PRO_0000152766"
FT REGION 1..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 573..595
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 9..43
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 275
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 299
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 321..323
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 329..330
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 337
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 339
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 492..493
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 495
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 499
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT BINDING 548..551
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 86
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 139
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15046"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 588
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 589
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 592
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 594
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 595 AA; 67840 MW; 055889E87C11AA97 CRC64;
MATLQESEVK VDGEQKLSKN ELKRRLKAEK KLAEKEAKQK ELSEKQLNQT ASAPNHTADN
GVGAEEETLD PNQYYKIRSQ AVQQLKVTGE DPYPHKFHVD ISLTQFIQEY SHLQPGDHLT
DVTLKVAGRI HAKRASGGKL IFYDLRGEGV KLQVMANSRN YKSEEEFVHI NNKLRRGDII
GVEGNPGKTK KGELSIIPQE ITLLSPCLHM LPHLHFGLKD KETRYRQRYL DLILNDFVRQ
KFIVRSKIIT YIRSFLDELG FLEIETPMMN IIPGGAVAKP FITYHNELDM NLYMRIAPEL
YHKMLVVGGI DRVYEIGRQF RNEGIDLTHN PEFTTCEFYM AYADYHDLME ITEKMLSGMV
KSITGSYKIT YHPDGPEGQA YEVDFTPPFR RISMVEELEK ALGVKLPETS LFETEETRKI
LDDICVAKAV ECPPPRTTAR LLDKLVGEFL EVTCISPTFI CDHPQIMSPL AKWHRSKEGL
TERFELFVMK KEICNAYTEL NDPVRQRQLF EEQAKAKAAG DDEAMFIDEN FCTALEYGLP
PTAGWGMGID RLTMFLTDSN NIKEVLLFPA MKPEDKKETA ATTETPESTE ASPSV
