CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-012475
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Lysine--tRNA ligase 
Protein Synonyms/Alias
 Lysyl-tRNA synthetase; LysRS 
Gene Name
 KARS 
Gene Synonyms/Alias
 KIAA0070 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
78VDPNQYYKIRSQAIHubiquitination[1, 2, 3]
88SQAIHQLKVNGEDPYacetylation[4]
127HLTDITLKVAGRIHAubiquitination[3]
141AKRASGGKLIFYDLRacetylation[4]
175EFIHINNKLRRGDIIubiquitination[3]
192QGNPGKTKKGELSIIubiquitination[3]
305IAPELYHKMLVVGGIubiquitination[1, 3, 5, 6]
363KMVSGMVKHITGSYKubiquitination[1, 3]
402NMVEELEKALGMKLPacetylation[4]
402NMVEELEKALGMKLPubiquitination[3]
407LEKALGMKLPETNLFubiquitination[3, 6]
421FETEETRKILDDICVubiquitination[1, 3, 6]
430LDDICVAKAVECPPPubiquitination[3, 5]
492RFELFVMKKEICNAYubiquitination[1, 3]
493FELFVMKKEICNAYTubiquitination[3, 6]
517QLFEEQAKAKAAGDDubiquitination[3, 6]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [5] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 
Functional Description
 Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of diadenosine oligophosphate (Ap4A), a signaling molecule involved in the activation of MITF transcriptional activity. Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation. 
Sequence Annotation
 NP_BIND 323 325 ATP.
 NP_BIND 331 332 ATP.
 NP_BIND 494 495 ATP.
 NP_BIND 550 553 ATP.
 METAL 487 487 Calcium.
 METAL 494 494 Calcium.
 BINDING 277 277 Substrate; via carbonyl oxygen.
 BINDING 301 301 Substrate.
 BINDING 339 339 Substrate.
 BINDING 341 341 Substrate.
 BINDING 497 497 Substrate.
 BINDING 501 501 Substrate.
 MOD_RES 2 2 N-acetylalanine.
 MOD_RES 88 88 N6-acetyllysine.
 MOD_RES 141 141 N6-acetyllysine.
 MOD_RES 596 596 Phosphoserine (By similarity).  
Keyword
 3D-structure; Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding; Cell membrane; Charcot-Marie-Tooth disease; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; Host-virus interaction; Ligase; Membrane; Metal-binding; Mitochondrion; Neuropathy; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Protein biosynthesis; Reference proteome; Secreted. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 597 AA 
Protein Sequence
MAAVQAAEVK VDGSEPKLSK NELKRRLKAE KKVAEKEAKQ KELSEKQLSQ ATAAATNHTT 60
DNGVGPEEES VDPNQYYKIR SQAIHQLKVN GEDPYPHKFH VDISLTDFIQ KYSHLQPGDH 120
LTDITLKVAG RIHAKRASGG KLIFYDLRGE GVKLQVMANS RNYKSEEEFI HINNKLRRGD 180
IIGVQGNPGK TKKGELSIIP YEITLLSPCL HMLPHLHFGL KDKETRYRQR YLDLILNDFV 240
RQKFIIRSKI ITYIRSFLDE LGFLEIETPM MNIIPGGAVA KPFITYHNEL DMNLYMRIAP 300
ELYHKMLVVG GIDRVYEIGR QFRNEGIDLT HNPEFTTCEF YMAYADYHDL MEITEKMVSG 360
MVKHITGSYK VTYHPDGPEG QAYDVDFTPP FRRINMVEEL EKALGMKLPE TNLFETEETR 420
KILDDICVAK AVECPPPRTT ARLLDKLVGE FLEVTCINPT FICDHPQIMS PLAKWHRSKE 480
GLTERFELFV MKKEICNAYT ELNDPMRQRQ LFEEQAKAKA AGDDEAMFID ENFCTALEYG 540
LPPTAGWGMG IDRVAMFLTD SNNIKEVLLF PAMKPEDKKE NVATTDTLES TTVGTSV 597 
Gene Ontology
 GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IEA:Compara.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
 GO:0015630; C:microtubule cytoskeleton; IDA:HPA.
 GO:0005759; C:mitochondrial matrix; TAS:Reactome.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0016597; F:amino acid binding; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004824; F:lysine-tRNA ligase activity; IDA:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0000049; F:tRNA binding; NAS:UniProtKB.
 GO:0015966; P:diadenosine tetraphosphate biosynthetic process; IEA:Compara.
 GO:0006430; P:lysyl-tRNA aminoacylation; IDA:UniProtKB.
 GO:0008033; P:tRNA processing; NAS:UniProtKB.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR004364; aa-tRNA-synt_II.
 IPR018150; aa-tRNA-synt_II-like.
 IPR006195; aa-tRNA-synth_II.
 IPR002313; Lys-tRNA-ligase_II.
 IPR018149; Lys-tRNA-synth_II_C.
 IPR012340; NA-bd_OB-fold.
 IPR004365; NA-bd_OB_tRNA-helicase. 
Pfam
 PF00152; tRNA-synt_2
 PF01336; tRNA_anti 
SMART
  
PROSITE
 PS50862; AA_TRNA_LIGASE_II 
PRINTS
 PR00982; TRNASYNTHLYS.