UniProt Accession

 SYEP_HUMAN; P07814; A0AVA9; B9EGH3; Q05BP6; Q05DF8; Q5DSM1; Q5H9S5; Q6PD57; Q86X73 

Genbank Protein ID

 CR933648; AC103590; BC015494; BC034797; BC046156; BC058921; BC126275; BC136465; X54326; AY493416; X07466 

Genbank Nucleotide ID

 CAI45949.1; AAH15494.1; AAH34797.1; AAH46156.1; AAH58921.1; AAI26276.1; AAI36466.1; CAA38224.1; AAS72877.1; CAA30354.1 

Protein Name

 Bifunctional glutamate/proline--tRNA ligase 

Protein Synonyms/Alias

 Bifunctional aminoacyl-tRNA synthetase; Cell proliferation-inducing gene 32 protein; Glutamatyl-prolyl-tRNA synthetase; Glutamate--tRNA ligase; Glutamyl-tRNA synthetase; GluRS; Proline--tRNA ligase; Prolyl-tRNA synthetase 

Gene Name

 EPRS 

Gene Synonyms/Alias

 GLNS; PARS; QARS; QPRS; PIG32 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
139	AAWQEQLKQKKAPVH	ubiquitination	[1]
173	KWDVSTTKARVAPEK	ubiquitination	[2]
197	LPGAEMGKVTVRFPP	ubiquitination	[2]
229	QHYQVNFKGKLIMRF	ubiquitination	[3, 4, 5]
231	YQVNFKGKLIMRFDD	ubiquitination	[2]
243	FDDTNPEKEKEDFEK	acetylation	[6, 7]
245	DTNPEKEKEDFEKVI	acetylation	[7]
282	TIMKYAEKLIQEGKA	acetylation	[6]
288	EKLIQEGKAYVDDTP	ubiquitination	[1, 2, 8, 9]
300	DTPAEQMKAEREQRI	acetylation	[6, 7, 10, 11]
300	DTPAEQMKAEREQRI	malonylation	[12]
370	PHPRTGNKYNVYPTY	ubiquitination	[2]
417	IEALGIRKPYIWEYS	acetylation	[10, 11]
417	IEALGIRKPYIWEYS	ubiquitination	[2]
435	LNNTVLSKRKLTWFV	ubiquitination	[1, 2, 4, 5, 7]
472	GMTVEGLKQFIAAQG	ubiquitination	[1, 2, 4, 7, 8, 9]
497	DKIWAFNKKVIDPVA	acetylation	[6, 7, 10, 11]
498	KIWAFNKKVIDPVAP	acetylation	[7, 10]
512	PRYVALLKKEVIPVN	ubiquitination	[4]
528	PEAQEEMKEVAKHPK	acetylation	[6]
535	KEVAKHPKNPEVGLK	acetylation	[10, 11]
535	KEVAKHPKNPEVGLK	ubiquitination	[4, 5]
542	KNPEVGLKPVWYSPK	acetylation	[10, 11]
542	KNPEVGLKPVWYSPK	ubiquitination	[2, 7]
599	AKLNLENKDYKKTTK	acetylation	[6, 7]
637	ITKPVLGKDEDFKQY	acetylation	[6, 10]
666	PCLKDLKKGDIIQLQ	ubiquitination	[2, 7]
708	YIPDGHTKEMPTSGS	ubiquitination	[2]
782	EDVDAAVKQLLSLKA	acetylation	[6]
782	EDVDAAVKQLLSLKA	ubiquitination	[4, 5]
788	VKQLLSLKAEYKEKT	acetylation	[6, 7, 10, 11]
849	AEKSPKAKINEAVEC	ubiquitination	[2, 7]
861	VECLLSLKAQYKEKT	acetylation	[7]
861	VECLLSLKAQYKEKT	ubiquitination	[2, 4, 5]
902	GLETPEAKVLFDKVA	ubiquitination	[5]
943	LQLKAQYKSLIGVEY	ubiquitination	[4, 5]
961	SATGAEDKDKKKKEK	acetylation	[6]
991	GQRKDPSKNQGGGLS	ubiquitination	[1]
1009	AGEGQGPKKQTRLGL	ubiquitination	[1, 7]
1010	GEGQGPKKQTRLGLE	ubiquitination	[2]
1070	FFDAEIKKLGVENCY	ubiquitination	[1]
1109	AWVTRSGKTELAEPI	ubiquitination	[1, 2, 9]
1132	VMYPAYAKWVQSHRD	ubiquitination	[2, 4, 7]
1143	SHRDLPIKLNQWCNV	ubiquitination	[2, 5, 7]
1156	NVVRWEFKHPQPFLR	acetylation	[6, 7, 10]
1156	NVVRWEFKHPQPFLR	ubiquitination	[2]
1361	KFNHWELKGVPIRLE	ubiquitination	[1, 8]
1375	EVGPRDMKSCQFVAV	ubiquitination	[1, 2, 5, 7]
1389	VRRDTGEKLTVAENE	acetylation	[6, 7]
1389	VRRDTGEKLTVAENE	ubiquitination	[1, 9]
1435	NTMEDFQKILDSGKI	ubiquitination	[4, 5]
1477	GAPSMGAKSLCIPFK	ubiquitination	[2]
1484	KSLCIPFKPLCELQP	ubiquitination	[2]
1503	VCGKNPAKYYTLFGR	acetylation	[10, 11]
1503	VCGKNPAKYYTLFGR	ubiquitination	[4, 5]

Reference

 [1] 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]
 [2] 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]
 [3] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
 [4] 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]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] 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]
 [7] 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]
 [8] 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]
 [9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [10] 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]
 [11] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [12] The first identification of lysine malonylation substrates and its regulatory enzyme.
 Peng C, Lu Z, Xie Z, Cheng Z, Chen Y, Tan M, Luo H, Zhang Y, He W, Yang K, Zwaans BM, Tishkoff D, Ho L, Lombard D, He TC, Dai J, Verdin E, Ye Y, Zhao Y.
 Mol Cell Proteomics. 2011 Dec;10(12):M111.012658. [PMID: 21908771] 

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. 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 959 991 Charged.
 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.
 MOD_RES 300 300 N6-malonyllysine; alternate.
 MOD_RES 417 417 N6-acetyllysine.
 MOD_RES 498 498 N6-acetyllysine.
 MOD_RES 535 535 N6-acetyllysine.
 MOD_RES 542 542 N6-acetyllysine.
 MOD_RES 637 637 N6-acetyllysine.
 MOD_RES 788 788 N6-acetyllysine.
 MOD_RES 872 872 Phosphotyrosine.
 MOD_RES 882 882 Phosphoserine.
 MOD_RES 885 885 Phosphoserine.
 MOD_RES 886 886 Phosphoserine; by CDK5.
 MOD_RES 891 891 Phosphoserine.
 MOD_RES 898 898 Phosphothreonine.
 MOD_RES 999 999 Phosphoserine.
 MOD_RES 1000 1000 Phosphoserine.
 MOD_RES 1503 1503 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Complete proteome; Cytoplasm; 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

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004818; F:glutamate-tRNA ligase activity; TAS:Reactome.
 GO:0004827; F:proline-tRNA ligase activity; TAS:Reactome.
 GO:0035613; F:RNA stem-loop binding; IDA: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.
 GO:0006461; P:protein complex assembly; TAS:ProtInc.
 GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome. 

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.
 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

 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.