Search Results

Overview

Uniprot IDP07814
Protein NameBifunctional glutamate/proline--tRNA ligase
Gene NameEPRS1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1009 AGEGQGPKKQTRLGL
1010 GEGQGPKKQTRLGLE
1326 DKEALIAKCNDYRRR
173 KWDVSTTKARVAPEK
186 EKKQDVGKFVELPGA
417 IEALGIRKPYIWEYS
435 LNNTVLSKRKLTWFV
498 KIWAFNKKVIDPVAP
512 PRYVALLKKEVIPVN
513 RYVALLKKEVIPVNV
542 KNPEVGLKPVWYSPK
593 KIISLDAKLNLENKD
637 ITKPVLGKDEDFKQY
693 PVSPYSCKEAPCVLI
725 KTKVEATKNETSAPF
733 NETSAPFKERPTPSL
907 EAKVLFDKVASQGEV
939 VQELLQLKAQYKSLI
961 SATGAEDKDKKKKEK
974 EKENKSEKQNKPQKQ
980 EKQNKPQKQNDGQRK
987 KQNDGQRKDPSKNQG
991 GQRKDPSKNQGGGLS

Function

Multifunctional protein which primarily functions within the aminoacyl-tRNA synthetase multienzyme complex, also known as multisynthetase complex. Within the complex it catalyzes the attachment of both L-glutamate and L-proline to their cognate tRNAs in a two-step reaction where the amino acid is first activated by ATP to form a covalent intermediate with AMP. Subsequently, the activated amino acid is transferred to the acceptor end of the cognate tRNA to form L-glutamyl-tRNA(Glu) and L-prolyl-tRNA(Pro) (PubMed:23263184, PubMed:24100331, PubMed:29576217, PubMed:3290852, PubMed:37212275). Upon interferon-gamma stimulation, EPRS1 undergoes phosphorylation, causing its dissociation from the aminoacyl-tRNA synthetase multienzyme complex. It is recruited to form the GAIT complex, which binds to stem loop-containing GAIT elements found in the 3'-UTR of various inflammatory mRNAs, such as ceruloplasmin. The GAIT complex inhibits the translation of these mRNAs, allowing interferon-gamma to redirect the function of EPRS1 from protein synthesis to translation inhibition in specific cell contexts (PubMed:15479637, PubMed:23071094). Furthermore, it can function as a downstream effector in the mTORC1 signaling pathway, by promoting the translocation of SLC27A1 from the cytoplasm to the plasma membrane where it mediates the uptake of long-chain fatty acid by adipocytes. Thereby, EPRS1 also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239)

Protein Sequence

10 MATLSLTVNS 20 GDPPLGALLA 30 VEHVKDDVSI 40 SVEEGKENIL 50 HVSENVIFTD 60 VNSILRYLAR 70 VATTAGLYGS 80 NLMEHTEIDH 90 WLEFSATKLS 100 SCDSFTSTIN 110 ELNHCLSLRT 120 YLVGNSLSLA 130 DLCVWATLKG 140 NAAWQEQLKQ 150 KKAPVHVKRW 160 FGFLEAQQAF 170 QSVGTKWDVS 180 TTKARVAPEK 190 KQDVGKFVEL 200 PGAEMGKVTV 210 RFPPEASGYL 220 HIGHAKAALL 230 NQHYQVNFKG 240 KLIMRFDDTN 250 PEKEKEDFEK 260 VILEDVAMLH 270 IKPDQFTYTS 280 DHFETIMKYA 290 EKLIQEGKAY 300 VDDTPAEQMK 310 AEREQRIDSK 320 HRKNPIEKNL 330 QMWEEMKKGS 340 QFGQSCCLRA 350 KIDMSSNNGC 360 MRDPTLYRCK 370 IQPHPRTGNK 380 YNVYPTYDFA 390 CPIVDSIEGV 400 THALRTTEYH 410 DRDEQFYWII 420 EALGIRKPYI 430 WEYSRLNLNN 440 TVLSKRKLTW 450 FVNEGLVDGW 460 DDPRFPTVRG 470 VLRRGMTVEG 480 LKQFIAAQGS 490 SRSVVNMEWD 500 KIWAFNKKVI 510 DPVAPRYVAL 520 LKKEVIPVNV 530 PEAQEEMKEV 540 AKHPKNPEVG 550 LKPVWYSPKV 560 FIEGADAETF 570 SEGEMVTFIN 580 WGNLNITKIH 590 KNADGKIISL 600 DAKLNLENKD 610 YKKTTKVTWL 620 AETTHALPIP 630 VICVTYEHLI 640 TKPVLGKDED 650 FKQYVNKNSK 660 HEELMLGDPC 670 LKDLKKGDII 680 QLQRRGFFIC 690 DQPYEPVSPY 700 SCKEAPCVLI 710 YIPDGHTKEM 720 PTSGSKEKTK 730 VEATKNETSA 740 PFKERPTPSL 750 NNNCTTSEDS 760 LVLYNRVAVQ 770 GDVVRELKAK 780 KAPKEDVDAA 790 VKQLLSLKAE 800 YKEKTGQEYK 810 PGNPPAEIGQ 820 NISSNSSASI 830 LESKSLYDEV 840 AAQGEVVRKL 850 KAEKSPKAKI 860 NEAVECLLSL 870 KAQYKEKTGK 880 EYIPGQPPLS 890 QSSDSSPTRN 900 SEPAGLETPE 910 AKVLFDKVAS 920 QGEVVRKLKT 930 EKAPKDQVDI 940 AVQELLQLKA 950 QYKSLIGVEY 960 KPVSATGAED 970 KDKKKKEKEN 980 KSEKQNKPQK 990 QNDGQRKDPS 1000 KNQGGGLSSS 1010 GAGEGQGPKK 1020 QTRLGLEAKK 1030 EENLADWYSQ 1040 VITKSEMIEY 1050 HDISGCYILR 1060 PWAYAIWEAI 1070 KDFFDAEIKK 1080 LGVENCYFPM 1090 FVSQSALEKE 1100 KTHVADFAPE 1110 VAWVTRSGKT 1120 ELAEPIAIRP 1130 TSETVMYPAY 1140 AKWVQSHRDL 1150 PIKLNQWCNV 1160 VRWEFKHPQP 1170 FLRTREFLWQ 1180 EGHSAFATME 1190 EAAEEVLQIL 1200 DLYAQVYEEL 1210 LAIPVVKGRK 1220 TEKEKFAGGD 1230 YTTTIEAFIS 1240 ASGRAIQGGT 1250 SHHLGQNFSK 1260 MFEIVFEDPK 1270 IPGEKQFAYQ 1280 NSWGLTTRTI 1290 GVMTMVHGDN 1300 MGLVLPPRVA 1310 CVQVVIIPCG 1320 ITNALSEEDK 1330 EALIAKCNDY 1340 RRRLLSVNIR 1350 VRADLRDNYS 1360 PGWKFNHWEL 1370 KGVPIRLEVG 1380 PRDMKSCQFV 1390 AVRRDTGEKL 1400 TVAENEAETK 1410 LQAILEDIQV 1420 TLFTRASEDL 1430 KTHMVVANTM 1440 EDFQKILDSG 1450 KIVQIPFCGE 1460 IDCEDWIKKT 1470 TARDQDLEPG 1480 APSMGAKSLC 1490 IPFKPLCELQ 1500 PGAKCVCGKN 1510 PAKYYTLFGR SY

Gene Ontology

Classification GO ID Description
Cellular Component GO:0017101 aminoacyl-tRNA synthetase multienzyme complex
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0097452 GAIT complex
Cellular Component GO:0016020 membrane
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:1990904 ribonucleoprotein complex
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0004818 glutamate-tRNA ligase activity
Molecular Function GO:0051020 GTPase binding
Molecular Function GO:0042802 identical protein binding
Molecular Function GO:0004827 proline-tRNA ligase activity
Molecular Function GO:0042803 protein homodimerization activity
Molecular Function GO:0035613 RNA stem-loop binding
Molecular Function GO:0008270 zinc ion binding
Biological Process GO:0032869 cellular response to insulin stimulus
Biological Process GO:0071346 cellular response to type II interferon
Biological Process GO:0006424 glutamyl-tRNA aminoacylation
Biological Process GO:1901194 negative regulation of formation of translation preinitiation complex
Biological Process GO:0017148 negative regulation of translation
Biological Process GO:0006433 prolyl-tRNA aminoacylation
Biological Process GO:0140212 regulation of long-chain fatty acid import into cell
Biological Process GO:0006418 tRNA aminoacylation for protein translation

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[4] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[5] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[6] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[7] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.