CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-016845
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Bifunctional glutamate/proline--tRNA ligase 
Protein Synonyms/Alias
 Bifunctional aminoacyl-tRNA synthetase; Glutamate--tRNA ligase; Glutamyl-tRNA synthetase; GluRS; Proline--tRNA ligase; Prolyl-tRNA synthetase; ProRS 
Gene Name
 Eprs 
Gene Synonyms/Alias
 Qprs 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
36SISVEEGKENLLRVSubiquitination[1]
142QEHLKQNKTLVHVKRacetylation[2]
166AFRSVGTKWDVSGNRubiquitination[1]
197LPGAEMGKVTVRFPPubiquitination[1]
229QHYQVNFKGKLIMRFubiquitination[1]
282TIMKYAEKLIQEGKAacetylation[3]
300DTPAEQMKAEREQRTacetylation[2, 3, 4, 5]
360DPTLYRCKIQPHPRTubiquitination[1]
417IEALGIRKPYIWEYSacetylation[2, 3]
435LNNTVLSKRKLTWFVubiquitination[1]
497DKIWAFNKKVIDPVAacetylation[5]
528LDAQEEMKEVARHPKacetylation[5]
535KEVARHPKNPDVGLKubiquitination[1]
542KNPDVGLKPVWYSPKacetylation[2, 3, 5]
782EDIDAAVKQLLTLKAubiquitination[1]
788VKQLLTLKAEYKEKTacetylation[2, 5]
800EKTGQEYKPGNPSAAacetylation[5]
829ESTSLYNKVAAQGEVubiquitination[1]
861VECLLSLKAEYKEKTacetylation[2, 3]
925LKAEKASKDQVDSAVubiquitination[1]
939VQELLQLKAQYKSLTacetylation[5]
939VQELLQLKAQYKSLTubiquitination[1]
961SATGAEDKDKKKKEKacetylation[5]
1009AGEGQGPKKQTRLGLubiquitination[1, 6]
1091QAALEKEKNHIEDFAubiquitination[1]
1109AWVTRSGKTELAEPIubiquitination[1]
1156NVVRWEFKHPQPFLRubiquitination[1]
1250HLGQNFSKMCEIVFEacetylation[3]
1375EVGPRDMKSCQFVAVubiquitination[1]
1389VRRDTGEKLTIAEKEacetylation[2]
1395EKLTIAEKEAEAKLEacetylation[2]
1395EKLTIAEKEAEAKLEubiquitination[1]
1403EAEAKLEKVLEDIQLubiquitination[1]
1435NTLEDFQKVLDAGKVubiquitination[1]
1503VCGKNPAKFYTLFGRacetylation[3]
Reference
 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [2] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [3] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [4] Quantitative assessment of the impact of the gut microbiota on lysine epsilon-acetylation of host proteins using gnotobiotic mice.
 Simon GM, Cheng J, Gordon JI.
 Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11133-8. [PMID: 22733758]
 [5] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [6] Synaptic protein ubiquitination in rat brain revealed by antibody-based ubiquitome analysis.
 Na CH, Jones DR, Yang Y, Wang X, Xu Y, Peng J.
 J Proteome Res. 2012 Sep 7;11(9):4722-32. [PMID: 22871113
Functional Description
 Catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma- induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. 
Sequence Annotation
 DOMAIN 749 805 WHEP-TRS 1.
 DOMAIN 822 878 WHEP-TRS 2.
 DOMAIN 900 956 WHEP-TRS 3.
 NP_BIND 432 436 ATP (By similarity).
 REGION 164 759 Glutamate--tRNA ligase.
 REGION 760 956 3 X 57 AA approximate repeats.
 REGION 1007 1512 Proline--tRNA ligase.
 MOTIF 204 214 "HIGH" region.
 MOTIF 432 436 "KMSKS" region.
 BINDING 211 211 ATP (By similarity).
 BINDING 398 398 ATP (By similarity).
 MOD_RES 300 300 N6-acetyllysine; alternate (By
 MOD_RES 300 300 N6-malonyllysine; alternate (By
 MOD_RES 417 417 N6-acetyllysine (By similarity).
 MOD_RES 498 498 N6-acetyllysine (By similarity).
 MOD_RES 535 535 N6-acetyllysine (By similarity).
 MOD_RES 542 542 N6-acetyllysine (By similarity).
 MOD_RES 637 637 N6-acetyllysine (By similarity).
 MOD_RES 788 788 N6-acetyllysine (By similarity).
 MOD_RES 872 872 Phosphotyrosine (By similarity).
 MOD_RES 885 885 Phosphoserine (By similarity).
 MOD_RES 999 999 Phosphoserine.
 MOD_RES 1503 1503 N6-acetyllysine (By similarity).  
Keyword
 Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Complete proteome; Ligase; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; Polymorphism; Protein biosynthesis; Reference proteome; Repeat; RNA-binding; Translation regulation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1512 AA 
Protein Sequence
MAALCLTVNA GNPPLEALLA VEHVKGDVSI SVEEGKENLL RVSETVAFTD VNSILRYLAR 60
IATTSGLYGT NLMEHTEIDH WLEFSATKLS SCDRLTSAIN ELNHCLSLRT YLVGNSLTLA 120
DLCVWATLKG SAAWQEHLKQ NKTLVHVKRW FGFLEAQQAF RSVGTKWDVS GNRATVAPDK 180
KQDVGKFVEL PGAEMGKVTV RFPPEASGYL HIGHAKAALL NQHYQVNFKG KLIMRFDDTN 240
PEKEKEDFEK VILEDVAMLH IKPDQFTYTS DHFETIMKYA EKLIQEGKAY VDDTPAEQMK 300
AEREQRTESK HRKNSVEKNL QMWEEMKKGS QFGQSCCLRA KIDMSSNNGC MRDPTLYRCK 360
IQPHPRTGNK YNVYPTYDFA CPIVDSIEGV THALRTTEYH DRDEQFYWII EALGIRKPYI 420
WEYSRLNLNN TVLSKRKLTW FVNEGLVDGW DDPRFPTVRG VLRRGMTVEG LKQFIAAQGS 480
SRSVVNMEWD KIWAFNKKVI DPVAPRYVAL LKKEVVPVNV LDAQEEMKEV ARHPKNPDVG 540
LKPVWYSPKV FIEGADAETF SEGEMVTFIN WGNINITKIH KNADGKITSL DAKLNLENKD 600
YKKTTKITWL AESTHALSIP AVCVTYEHLI TKPVLGKDED FKQYINKDSK HEELMLGDPC 660
LKDLKKGDII QLQRRGFFIC DQPYEPVSPY SCREAPCILI YIPDGHTKEM PTSGSKEKTK 720
VEISKKETSS APKERPAPAV SSTCATAEDS SVLYSRVAVQ GDVVRELKAK KAPKEDIDAA 780
VKQLLTLKAE YKEKTGQEYK PGNPSAAAVQ TVSTKSSSNT VESTSLYNKV AAQGEVVRKL 840
KAEKAPKAKV TEAVECLLSL KAEYKEKTGK DYVPGQPPAS QNSHSNPVSN AQPAGAEKPE 900
AKVLFDRVAC QGEVVRKLKA EKASKDQVDS AVQELLQLKA QYKSLTGIEY KPVSATGAED 960
KDKKKKEKEN KSEKQNKPQK QNDGQGKDSS KSQGSGLSSG GAGEGQGPKK QTRLGLEAKK 1020
EENLAEWYSQ VITKSEMIEY YDVSGCYILR PWSYSIWESI KDFFDAEIKK LGVENCYFPI 1080
FVSQAALEKE KNHIEDFAPE VAWVTRSGKT ELAEPIAIRP TSETVMYPAY AKWVQSHRDL 1140
PVRLNQWCNV VRWEFKHPQP FLRTREFLWQ EGHSAFATFE EAADEVLQIL ELYARVYEEL 1200
LAIPVVRGRK TEKEKFAGGD YTTTIEAFIS ASGRAIQGAT SHHLGQNFSK MCEIVFEDPK 1260
TPGEKQFAYQ CSWGLTTRTI GVMVMVHGDN MGLVLPPRVA SVQVVVIPCG ITNALSEEDR 1320
EALMAKCNEY RRRLLGANIR VRVDLRDNYS PGWKFNHWEL KGVPVRLEVG PRDMKSCQFV 1380
AVRRDTGEKL TIAEKEAEAK LEKVLEDIQL NLFTRASEDL KTHMVVSNTL EDFQKVLDAG 1440
KVAQIPFCGE IDCEDWIKKM TARDQDVEPG APSMGAKSLC IPFNPLCELQ PGAMCVCGKN 1500
PAKFYTLFGR SY 1512 
Gene Ontology
 GO:0005737; C:cytoplasm; IEA:InterPro.
 GO:0030529; C:ribonucleoprotein complex; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004818; F:glutamate-tRNA ligase activity; IEA:EC.
 GO:0004827; F:proline-tRNA ligase activity; IEA:EC.
 GO:0035613; F:RNA stem-loop binding; ISS:UniProtKB.
 GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB.
 GO:0006424; P:glutamyl-tRNA aminoacylation; IEA:InterPro.
 GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
 GO:0006433; P:prolyl-tRNA aminoacylation; IEA:InterPro. 
Interpro
 IPR002314; aa-tRNA-synt_IIb_cons-dom.
 IPR001412; aa-tRNA-synth_I_CS.
 IPR006195; aa-tRNA-synth_II.
 IPR004154; Anticodon-bd.
 IPR004526; Glu-tRNA-synth_Ib_arc/euk.
 IPR000924; Glu/Gln-tRNA-synth_Ib.
 IPR020061; Glu/Gln-tRNA-synth_Ib_a-bdl.
 IPR020058; Glu/Gln-tRNA-synth_Ib_cat-dom.
 IPR020059; Glu/Gln-tRNA-synth_Ib_codon-bd.
 IPR010987; Glutathione-S-Trfase_C-like.
 IPR004046; GST_C.
 IPR004499; Pro-tRNA-ligase_IIa_arc-type.
 IPR016061; Pro-tRNA_ligase_II_C.
 IPR017449; Pro-tRNA_synth_II.
 IPR020056; Rbsml_L25/Gln-tRNA_synth_b-brl.
 IPR011035; Ribosomal_L25/Gln-tRNA_synth.
 IPR014729; Rossmann-like_a/b/a_fold.
 IPR009068; S15_NS1_RNA-bd.
 IPR000738; WHEP-TRS. 
Pfam
 PF00043; GST_C
 PF03129; HGTP_anticodon
 PF09180; ProRS-C_1
 PF00749; tRNA-synt_1c
 PF03950; tRNA-synt_1c_C
 PF00587; tRNA-synt_2b
 PF00458; WHEP-TRS 
SMART
 SM00946; ProRS-C_1
 SM00991; WHEP-TRS 
PROSITE
 PS00178; AA_TRNA_LIGASE_I
 PS50862; AA_TRNA_LIGASE_II
 PS00762; WHEP_TRS_1
 PS51185; WHEP_TRS_2 
PRINTS
 PR00987; TRNASYNTHGLU.