SYEP_HUMAN
ID SYEP_HUMAN Reviewed; 1512 AA.
AC P07814; A0AVA9; B9EGH3; Q05BP6; Q05DF8; Q5DSM1; Q5H9S5; Q6PD57; Q86X73;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 5.
DT 03-AUG-2022, entry version 244.
DE RecName: Full=Bifunctional glutamate/proline--tRNA ligase;
DE AltName: Full=Bifunctional aminoacyl-tRNA synthetase;
DE AltName: Full=Cell proliferation-inducing gene 32 protein;
DE AltName: Full=Glutamatyl-prolyl-tRNA synthetase;
DE Includes:
DE RecName: Full=Glutamate--tRNA ligase;
DE EC=6.1.1.17;
DE AltName: Full=Glutamyl-tRNA synthetase;
DE Short=GluRS;
DE Includes:
DE RecName: Full=Proline--tRNA ligase;
DE EC=6.1.1.15 {ECO:0000269|PubMed:23263184, ECO:0000269|PubMed:24100331};
DE AltName: Full=Prolyl-tRNA synthetase;
GN Name=EPRS1 {ECO:0000312|HGNC:HGNC:3418};
GN Synonyms=EPRS, GLNS, PARS, QARS, QPRS; ORFNames=PIG32;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS GLU-308 AND VAL-1043.
RC TISSUE=Bone marrow;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-308.
RC TISSUE=Brain, Duodenum, Eye, Lung, Placenta, and Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 54-1512, AND VARIANTS GLU-308 AND HIS-334.
RX PubMed=1988429; DOI=10.1016/s0021-9258(18)52315-2;
RA Fett R., Knippers R.;
RT "The primary structure of human glutaminyl-tRNA synthetase. A highly
RT conserved core, amino acid repeat regions, and homologies with translation
RT elongation factors.";
RL J. Biol. Chem. 266:1448-1455(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 62-1512, AND VARIANTS GLU-308 AND
RP HIS-334.
RA Kim J.W.;
RT "Identification of a proliferation inducing gene.";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 168-959, AND VARIANTS GLU-308 AND
RP HIS-334.
RC TISSUE=Cervix carcinoma;
RX PubMed=3290852; DOI=10.1093/nar/16.12.5391;
RA Thoemmes P., Fett R., Schray B., Kunze N., Knippers R.;
RT "The core region of human glutaminyl-tRNA synthetase homologies with the
RT Escherichia coli and yeast enzymes.";
RL Nucleic Acids Res. 16:5391-5406(1988).
RN [7]
RP FUNCTION.
RX PubMed=1756734; DOI=10.1002/j.1460-2075.1991.tb05005.x;
RA Cerini C., Kerjan P., Astier M., Gratecos D., Mirande M., Semeriva M.;
RT "A component of the multisynthetase complex is a multifunctional aminoacyl-
RT tRNA synthetase.";
RL EMBO J. 10:4267-4277(1991).
RN [8]
RP GENE STRUCTURE.
RX PubMed=1556743; DOI=10.1007/bf00163851;
RA Kaiser E., Eberhard D., Knippers R.;
RT "Exons encoding the highly conserved part of human glutaminyl-tRNA
RT synthetase.";
RL J. Mol. Evol. 34:45-53(1992).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=10791971; DOI=10.1083/jcb.149.3.567;
RA Ko Y.G., Kang Y.S., Kim E.K., Park S.G., Kim S.;
RT "Nucleolar localization of human methionyl-tRNA synthetase and its role in
RT ribosomal RNA synthesis.";
RL J. Cell Biol. 149:567-574(2000).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [11]
RP FUNCTION, AND IDENTIFICATION IN THE GAIT COMPLEX.
RX PubMed=15479637; DOI=10.1016/j.cell.2004.09.030;
RA Sampath P., Mazumder B., Seshadri V., Gerber C.A., Chavatte L., Kinter M.,
RA Ting S.M., Dignam J.D., Kim S., Driscoll D.M., Fox P.L.;
RT "Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific
RT silencing of translation.";
RL Cell 119:195-208(2004).
RN [12]
RP INTERACTION WITH DUS2L.
RX PubMed=15994936; DOI=10.1158/0008-5472.can-05-0600;
RA Kato T., Daigo Y., Hayama S., Ishikawa N., Yamabuki T., Ito T.,
RA Miyamoto M., Kondo S., Nakamura Y.;
RT "A novel human tRNA-dihydrouridine synthase involved in pulmonary
RT carcinogenesis.";
RL Cancer Res. 65:5638-5646(2005).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-898, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-872; SER-882; SER-885;
RP SER-886 AND THR-898, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19131329; DOI=10.1074/jbc.m809636200;
RA Kaminska M., Havrylenko S., Decottignies P., Gillet S., Le Marechal P.,
RA Negrutskii B., Mirande M.;
RT "Dissection of the structural organization of the aminoacyl-tRNA synthetase
RT complex.";
RL J. Biol. Chem. 284:6053-6060(2009).
RN [20]
RP SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=19289464; DOI=10.1074/jbc.m900480200;
RA Kaminska M., Havrylenko S., Decottignies P., Le Marechal P., Negrutskii B.,
RA Mirande M.;
RT "Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes in the
RT Cytoplasm of Human Cells.";
RL J. Biol. Chem. 284:13746-13754(2009).
RN [21]
RP PHOSPHORYLATION AT SER-886 AND SER-999, AND INTERACTION WITH SYNCRIP.
RX PubMed=19647514; DOI=10.1016/j.molcel.2009.05.028;
RA Arif A., Jia J., Mukhopadhyay R., Willard B., Kinter M., Fox P.L.;
RT "Two-site phosphorylation of EPRS coordinates multimodal regulation of
RT noncanonical translational control activity.";
RL Mol. Cell 35:164-180(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-882; SER-886 AND SER-891, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-300; LYS-417; LYS-498; LYS-535;
RP LYS-542; LYS-637; LYS-788 AND LYS-1503, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1000, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP MALONYLATION AT LYS-300.
RX PubMed=21908771; DOI=10.1074/mcp.m111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W.,
RA Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J.,
RA Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [27]
RP PHOSPHORYLATION AT SER-886.
RX PubMed=21220307; DOI=10.1073/pnas.1011275108;
RA Arif A., Jia J., Moodt R.A., DiCorleto P.E., Fox P.L.;
RT "Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent
RT kinase 5 dictates transcript-selective translational control.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:1415-1420(2011).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-886, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [29]
RP FUNCTION, RECONSTITUTION OF THE GAIT COMPLEX, AND MUTAGENESIS OF SER-886
RP AND SER-999.
RX PubMed=23071094; DOI=10.1128/mcb.01168-12;
RA Arif A., Chatterjee P., Moodt R.A., Fox P.L.;
RT "Heterotrimeric GAIT complex drives transcript-selective translation
RT inhibition in murine macrophages.";
RL Mol. Cell. Biol. 32:5046-5055(2012).
RN [30]
RP IDENTIFICATION IN THE MSC COMPLEX, INTERACTION WITH TARS3, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=24312579; DOI=10.1371/journal.pone.0081734;
RA Kim K., Park S.J., Na S., Kim J.S., Choi H., Kim Y.K., Paek E., Lee C.;
RT "Reinvestigation of aminoacyl-tRNA synthetase core complex by affinity
RT purification-mass spectrometry reveals TARSL2 as a potential member of the
RT complex.";
RL PLoS ONE 8:E81734-E81734(2013).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-355; SER-434; SER-747;
RP SER-882; SER-886; THR-898; SER-998 AND SER-1350, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [32]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [33]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1152, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Colon carcinoma;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [35]
RP FUNCTION, INTERACTION WITH SLC27A1, SUBCELLULAR LOCATION, TOPOLOGY, AND
RP PHOSPHORYLATION AT SER-999 BY RPS6KB1.
RX PubMed=28178239; DOI=10.1038/nature21380;
RA Arif A., Terenzi F., Potdar A.A., Jia J., Sacks J., China A., Halawani D.,
RA Vasu K., Li X., Brown J.M., Chen J., Kozma S.C., Thomas G., Fox P.L.;
RT "EPRS is a critical mTORC1-S6K1 effector that influences adiposity in
RT mice.";
RL Nature 542:357-361(2017).
RN [36]
RP INVOLVEMENT IN HLD15, VARIANTS HLD15 339-ARG--TYR-1512 DEL; ARG-1115;
RP THR-1126 AND SER-1160, AND CHARACTERIZATION OF VARIANTS HLD15 ARG-1115 AND
RP THR-1126.
RX PubMed=29576217; DOI=10.1016/j.ajhg.2018.02.011;
RA Mendes M.I., Gutierrez Salazar M., Guerrero K., Thiffault I.,
RA Salomons G.S., Gauquelin L., Tran L.T., Forget D., Gauthier M.S.,
RA Waisfisz Q., Smith D.E.C., Simons C., van der Knaap M.S., Marquardt I.,
RA Lemes A., Mierzewska H., Weschke B., Koehler W., Coulombe B., Wolf N.I.,
RA Bernard G.;
RT "Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA
RT Synthetase, Cause a Hypomyelinating Leukodystrophy.";
RL Am. J. Hum. Genet. 102:676-684(2018).
RN [37]
RP STRUCTURE BY NMR OF 749-805, AND RNA-BINDING.
RX PubMed=11123902; DOI=10.1021/bi001393h;
RA Jeong E.-J., Hwang G.-S., Kim K.H., Kim M.J., Kim S., Kim K.-S.;
RT "Structural analysis of multifunctional peptide motifs in human
RT bifunctional tRNA synthetase: identification of RNA-binding residues and
RT functional implications for tandem repeats.";
RL Biochemistry 39:15775-15782(2000).
RN [38] {ECO:0007744|PDB:4K86, ECO:0007744|PDB:4K87, ECO:0007744|PDB:4K88}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1000-1512 IN COMPLEXES WITH
RP SYNTHETIC INHIBITOR HALOFUGINONE; L-PROLINE; ZINC AND ADENOSINE, CATALYTIC
RP ACTIVITY, FUNCTION, SUBUNIT, AND MUTAGENESIS OF PHE-1097 AND ARG-1152.
RX PubMed=24100331; DOI=10.1107/s0907444913020556;
RA Son J., Lee E.H., Park M., Kim J.H., Kim J., Kim S., Jeon Y.H., Hwang K.Y.;
RT "Conformational changes in human prolyl-tRNA synthetase upon binding of the
RT substrates proline and ATP and the inhibitor halofuginone.";
RL Acta Crystallogr. D 69:2136-2145(2013).
RN [39] {ECO:0007744|PDB:4HVC}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1003-1512 IN COMPLEX WITH
RP SYNTHETIC INHIBITOR; ZINC AND ATP ANALOG, CATALYTIC ACTIVITY, FUNCTION, AND
RP SUBUNIT.
RX PubMed=23263184; DOI=10.1038/nature11774;
RA Zhou H., Sun L., Yang X.L., Schimmel P.;
RT "ATP-directed capture of bioactive herbal-based medicine on human tRNA
RT synthetase.";
RL Nature 494:121-124(2013).
RN [40] {ECO:0007744|PDB:5A34, ECO:0007744|PDB:5BMU}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-175, AND SUBUNIT.
RX PubMed=26472928; DOI=10.1074/jbc.m115.690867;
RA Cho H.Y., Maeng S.J., Cho H.J., Choi Y.S., Chung J.M., Lee S., Kim H.K.,
RA Kim J.H., Eom C.Y., Kim Y.G., Guo M., Jung H.S., Kang B.S., Kim S.;
RT "Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione
RT Transferase-homology Domains.";
RL J. Biol. Chem. 290:29313-29328(2015).
CC -!- FUNCTION: Multifunctional protein which is primarily part of the
CC aminoacyl-tRNA synthetase multienzyme complex, also know as
CC multisynthetase complex, that catalyzes the attachment of the cognate
CC amino acid to the corresponding tRNA in a two-step reaction: the amino
CC acid is first activated by ATP to form a covalent intermediate with AMP
CC and is then transferred to the acceptor end of the cognate tRNA
CC (PubMed:1756734, PubMed:24100331, PubMed:23263184). The phosphorylation
CC of EPRS1, induced by interferon-gamma, dissociates the protein from the
CC aminoacyl-tRNA synthetase multienzyme complex and recruits it to the
CC GAIT complex that binds to stem loop-containing GAIT elements in the
CC 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin), suppressing
CC their translation. Interferon-gamma can therefore redirect, in specific
CC cells, the EPRS1 function from protein synthesis to translation
CC inhibition (PubMed:15479637, PubMed:23071094). Also functions as an
CC effector of the mTORC1 signaling pathway by promoting, through SLC27A1,
CC the uptake of long-chain fatty acid by adipocytes. Thereby, it also
CC plays a role in fat metabolism and more indirectly influences lifespan
CC (PubMed:28178239). {ECO:0000269|PubMed:15479637,
CC ECO:0000269|PubMed:1756734, ECO:0000269|PubMed:23071094,
CC ECO:0000269|PubMed:23263184, ECO:0000269|PubMed:24100331,
CC ECO:0000269|PubMed:28178239}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-glutamate + tRNA(Glu) = AMP + diphosphate + L-
CC glutamyl-tRNA(Glu); Xref=Rhea:RHEA:23540, Rhea:RHEA-COMP:9663,
CC Rhea:RHEA-COMP:9680, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:78442, ChEBI:CHEBI:78520,
CC ChEBI:CHEBI:456215; EC=6.1.1.17;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-proline + tRNA(Pro) = AMP + diphosphate + L-prolyl-
CC tRNA(Pro); Xref=Rhea:RHEA:14305, Rhea:RHEA-COMP:9700, Rhea:RHEA-
CC COMP:9702, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:60039,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78532, ChEBI:CHEBI:456215;
CC EC=6.1.1.15; Evidence={ECO:0000269|PubMed:23263184,
CC ECO:0000269|PubMed:24100331};
CC -!- ACTIVITY REGULATION: Inhibited by halofuginone.
CC {ECO:0000269|PubMed:23263184, ECO:0000269|PubMed:24100331}.
CC -!- SUBUNIT: Homodimer (PubMed:24100331, PubMed:23263184). Part of the
CC aminoacyl-tRNA synthetase multienzyme complex, also know as
CC multisynthetase complex (MSC), that is composed of the tRNA ligases for
CC Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys
CC (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1)
CC and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18
CC (PubMed:24312579, PubMed:19131329, PubMed:19289464). Forms a linear
CC complex that contains MARS1, EEF1E1, EPRS1 and AIMP2 that is at the
CC core of the multisubunit complex (PubMed:26472928). Interacts with
CC TARS3 (PubMed:24312579). Interacts with DUS2L (PubMed:15994936).
CC Component of the GAIT complex which is composed of EPRS1, RPL13A and
CC GAPDH. For human, the complex assembly seems to be a two-step process
CC in which EPRS1 first associates with SYNCRIP to form a pre-GAIT complex
CC which is deficient in GAIT element binding (PubMed:15479637). Interacts
CC (phosphorylated at Ser-999) with SLC27A1; mediates the translocation of
CC SLC27A1 from the cytoplasm to the plasma membrane thereby increasing
CC the uptake of long-chain fatty acids (PubMed:28178239).
CC {ECO:0000269|PubMed:15479637, ECO:0000269|PubMed:15994936,
CC ECO:0000269|PubMed:19131329, ECO:0000269|PubMed:19289464,
CC ECO:0000269|PubMed:19647514, ECO:0000269|PubMed:23263184,
CC ECO:0000269|PubMed:24100331, ECO:0000269|PubMed:24312579,
CC ECO:0000269|PubMed:26472928, ECO:0000269|PubMed:28178239}.
CC -!- INTERACTION:
CC P07814; P07814: EPRS1; NbExp=2; IntAct=EBI-355315, EBI-355315;
CC P07814; Q8IWL3: HSCB; NbExp=4; IntAct=EBI-355315, EBI-1805738;
CC P07814; P41252: IARS1; NbExp=7; IntAct=EBI-355315, EBI-355303;
CC P07814; Q15046: KARS1; NbExp=4; IntAct=EBI-355315, EBI-356367;
CC P07814; P42695: NCAPD3; NbExp=4; IntAct=EBI-355315, EBI-722805;
CC P07814; O60506: SYNCRIP; NbExp=3; IntAct=EBI-355315, EBI-1024357;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10791971,
CC ECO:0000269|PubMed:19289464}. Membrane {ECO:0000269|PubMed:28178239};
CC Peripheral membrane protein {ECO:0000305|PubMed:19289464,
CC ECO:0000305|PubMed:28178239}. Note=Translocates from cytosol to
CC membranes upon phosphorylation at Ser-999.
CC {ECO:0000269|PubMed:19289464, ECO:0000269|PubMed:28178239}.
CC -!- DOMAIN: The WHEP-TRS domains are involved in RNA binding.
CC {ECO:0000250|UniProtKB:Q7SIA2}.
CC -!- PTM: Phosphorylated at Ser-886 by CDK5 (PubMed:19647514,
CC PubMed:21220307). Phosphorylated at Ser-999 by RPS6KB1; triggers EPRS1
CC release from the aminoacyl-tRNA synthetase multienzyme complex
CC (PubMed:19647514, PubMed:21220307, PubMed:28178239). In monocytes, the
CC IFN-gamma-induced sequential phosphorylation at Ser-886 and Ser-999
CC releases EPRS1 from the aminoacyl-tRNA synthetase multienzyme complex,
CC allowing its association with the GAIT complex. Phosphorylation at Ser-
CC 999 is specifically required for the RPL13A-mediated interaction of the
CC GAIT complex with eIF4G (PubMed:19647514, PubMed:21220307).
CC Phosphorylation at Ser-999 by RPS6KB1, is also induced by insulin
CC through activation of the mTORC1 signaling pathway and promotes the
CC interaction of EPRS1 with SLC27A1 (PubMed:28178239).
CC {ECO:0000269|PubMed:19647514, ECO:0000269|PubMed:21220307,
CC ECO:0000269|PubMed:28178239}.
CC -!- DISEASE: Leukodystrophy, hypomyelinating, 15 (HLD15) [MIM:617951]: An
CC autosomal recessive disorder characterized by hypomyelinating
CC leukodystrophy with thinning of the corpus callosum. Clinical features
CC include motor and cognitive impairment appearing in the first or second
CC decade of life, dystonia, ataxia, spasticity, and dysphagia. Most
CC patients develop severe optic atrophy, and some have hearing loss.
CC {ECO:0000269|PubMed:29576217}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class-I
CC aminoacyl-tRNA synthetase family. Glutamate--tRNA ligase type 2
CC subfamily. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the class-II
CC aminoacyl-tRNA synthetase family. {ECO:0000305}.
CC -!- CAUTION: Was originally thought to be a glutaminyl-tRNA synthetase.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH15494.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH34797.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH46156.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAH58921.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAS72877.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA30354.1; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305};
CC Sequence=CAA38224.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; CR933648; CAI45949.1; -; mRNA.
DR EMBL; AC103590; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015494; AAH15494.1; ALT_SEQ; mRNA.
DR EMBL; BC034797; AAH34797.1; ALT_SEQ; mRNA.
DR EMBL; BC046156; AAH46156.1; ALT_SEQ; mRNA.
DR EMBL; BC058921; AAH58921.1; ALT_SEQ; mRNA.
DR EMBL; BC126275; AAI26276.1; -; mRNA.
DR EMBL; BC136465; AAI36466.1; -; mRNA.
DR EMBL; X54326; CAA38224.1; ALT_INIT; mRNA.
DR EMBL; AY493416; AAS72877.1; ALT_INIT; mRNA.
DR EMBL; X07466; CAA30354.1; ALT_SEQ; mRNA.
DR CCDS; CCDS31027.1; -.
DR PIR; A38663; SYHUQT.
DR RefSeq; NP_004437.2; NM_004446.2.
DR PDB; 1FYJ; NMR; -; A=749-805.
DR PDB; 4HVC; X-ray; 2.00 A; A/B=1003-1512.
DR PDB; 4K86; X-ray; 2.40 A; A=1000-1512.
DR PDB; 4K87; X-ray; 2.30 A; A=1000-1512.
DR PDB; 4K88; X-ray; 2.62 A; A=1000-1512.
DR PDB; 5A1N; X-ray; 2.10 A; A=1-175.
DR PDB; 5A34; X-ray; 2.60 A; A/C/E/G=1-175.
DR PDB; 5A5H; X-ray; 2.32 A; A/C/E/G=1-175.
DR PDB; 5BMU; X-ray; 2.60 A; B/D/F/H=1-175.
DR PDB; 5V58; X-ray; 2.59 A; A=1003-1512.
DR PDB; 5VAD; X-ray; 2.36 A; A/B=998-1512.
DR PDB; 5Y6L; X-ray; 2.90 A; C=1-175.
DR PDB; 6IY6; X-ray; 3.60 A; E/F/K/L=1-157.
DR PDB; 7BBU; X-ray; 2.19 A; A=1000-1512.
DR PDB; 7OSY; X-ray; 2.23 A; A/B=1001-1512.
DR PDB; 7OSZ; X-ray; 2.46 A; A/B=1001-1512.
DR PDB; 7OT0; X-ray; 2.32 A; A/B=1001-1512.
DR PDB; 7OT1; X-ray; 2.71 A; A/B=1001-1512.
DR PDB; 7OT2; X-ray; 2.48 A; A/B=1001-1512.
DR PDB; 7OT3; X-ray; 2.53 A; A/B=1001-1512.
DR PDBsum; 1FYJ; -.
DR PDBsum; 4HVC; -.
DR PDBsum; 4K86; -.
DR PDBsum; 4K87; -.
DR PDBsum; 4K88; -.
DR PDBsum; 5A1N; -.
DR PDBsum; 5A34; -.
DR PDBsum; 5A5H; -.
DR PDBsum; 5BMU; -.
DR PDBsum; 5V58; -.
DR PDBsum; 5VAD; -.
DR PDBsum; 5Y6L; -.
DR PDBsum; 6IY6; -.
DR PDBsum; 7BBU; -.
DR PDBsum; 7OSY; -.
DR PDBsum; 7OSZ; -.
DR PDBsum; 7OT0; -.
DR PDBsum; 7OT1; -.
DR PDBsum; 7OT2; -.
DR PDBsum; 7OT3; -.
DR AlphaFoldDB; P07814; -.
DR SMR; P07814; -.
DR BioGRID; 108372; 312.
DR CORUM; P07814; -.
DR DIP; DIP-40825N; -.
DR IntAct; P07814; 75.
DR MINT; P07814; -.
DR STRING; 9606.ENSP00000355890; -.
DR BindingDB; P07814; -.
DR ChEMBL; CHEMBL3873; -.
DR DrugBank; DB02684; 5'-O-(L-Cysteinylsulfamoyl)adenosine.
DR DrugBank; DB02510; 5'-O-(L-Prolylsulfamoyl)adenosine.
DR DrugBank; DB03376; 5'-O-(N-(Alanyl)sulfamoyl)adenosine.
DR DrugBank; DB00142; Glutamic acid.
DR DrugBank; DB00172; Proline.
DR MoonProt; P07814; -.
DR GlyGen; P07814; 3 sites, 2 O-linked glycans (3 sites).
DR iPTMnet; P07814; -.
DR MetOSite; P07814; -.
DR PhosphoSitePlus; P07814; -.
DR SwissPalm; P07814; -.
DR BioMuta; EPRS; -.
DR DMDM; 288558855; -.
DR CPTAC; CPTAC-71; -.
DR CPTAC; CPTAC-72; -.
DR EPD; P07814; -.
DR jPOST; P07814; -.
DR MassIVE; P07814; -.
DR MaxQB; P07814; -.
DR PaxDb; P07814; -.
DR PeptideAtlas; P07814; -.
DR PRIDE; P07814; -.
DR ProteomicsDB; 52028; -.
DR Antibodypedia; 20734; 204 antibodies from 30 providers.
DR DNASU; 2058; -.
DR Ensembl; ENST00000366923.8; ENSP00000355890.3; ENSG00000136628.18.
DR GeneID; 2058; -.
DR KEGG; hsa:2058; -.
DR MANE-Select; ENST00000366923.8; ENSP00000355890.3; NM_004446.3; NP_004437.2.
DR UCSC; uc001hly.2; human.
DR CTD; 2058; -.
DR DisGeNET; 2058; -.
DR GeneCards; EPRS1; -.
DR HGNC; HGNC:3418; EPRS1.
DR HPA; ENSG00000136628; Low tissue specificity.
DR MalaCards; EPRS1; -.
DR MIM; 138295; gene.
DR MIM; 617951; phenotype.
DR neXtProt; NX_P07814; -.
DR OpenTargets; ENSG00000136628; -.
DR PharmGKB; PA27837; -.
DR VEuPathDB; HostDB:ENSG00000136628; -.
DR eggNOG; KOG1147; Eukaryota.
DR eggNOG; KOG4163; Eukaryota.
DR GeneTree; ENSGT00550000074815; -.
DR HOGENOM; CLU_001882_0_2_1; -.
DR InParanoid; P07814; -.
DR OMA; WDPKGNN; -.
DR OrthoDB; 809861at2759; -.
DR PhylomeDB; P07814; -.
DR TreeFam; TF300380; -.
DR BRENDA; 6.1.1.15; 2681.
DR BRENDA; 6.1.1.17; 2681.
DR PathwayCommons; P07814; -.
DR Reactome; R-HSA-2408522; Selenoamino acid metabolism.
DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation.
DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol.
DR SignaLink; P07814; -.
DR SIGNOR; P07814; -.
DR BioGRID-ORCS; 2058; 762 hits in 1079 CRISPR screens.
DR ChiTaRS; EPRS; human.
DR EvolutionaryTrace; P07814; -.
DR GeneWiki; EPRS; -.
DR GenomeRNAi; 2058; -.
DR Pharos; P07814; Tchem.
DR PRO; PR:P07814; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P07814; protein.
DR Bgee; ENSG00000136628; Expressed in parotid gland and 216 other tissues.
DR ExpressionAtlas; P07814; baseline and differential.
DR Genevisible; P07814; HS.
DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:CAFA.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0097452; C:GAIT complex; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004818; F:glutamate-tRNA ligase activity; TAS:Reactome.
DR GO; GO:0051020; F:GTPase binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004827; F:proline-tRNA ligase activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0035613; F:RNA stem-loop binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB.
DR GO; GO:0006424; P:glutamyl-tRNA aminoacylation; IEA:InterPro.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:0006433; P:prolyl-tRNA aminoacylation; IDA:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; TAS:ProtInc.
DR GO; GO:0140212; P:regulation of long-chain fatty acid import into cell; IMP:UniProtKB.
DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome.
DR CDD; cd00778; ProRS_core_arch_euk; 1.
DR Gene3D; 2.40.240.10; -; 2.
DR Gene3D; 3.30.110.30; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR Gene3D; 3.40.50.800; -; 1.
DR HAMAP; MF_02076; Glu_tRNA_synth_type2; 1.
DR HAMAP; MF_01571; Pro_tRNA_synth_type3; 1.
DR InterPro; IPR002314; aa-tRNA-synt_IIb.
DR InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004154; Anticodon-bd.
DR InterPro; IPR036621; Anticodon-bd_dom_sf.
DR InterPro; IPR004526; Glu-tRNA-synth_arc/euk.
DR InterPro; IPR000924; Glu/Gln-tRNA-synth.
DR InterPro; IPR020058; Glu/Gln-tRNA-synth_Ib_cat-dom.
DR InterPro; IPR020059; Glu/Gln-tRNA-synth_Ib_codon-bd.
DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR InterPro; IPR004046; GST_C.
DR InterPro; IPR004499; Pro-tRNA-ligase_IIa_arc-type.
DR InterPro; IPR016061; Pro-tRNA_ligase_II_C.
DR InterPro; IPR017449; Pro-tRNA_synth_II.
DR InterPro; IPR033721; ProRS_core_arch_euk.
DR InterPro; IPR020056; Rbsml_L25/Gln-tRNA_synth_N.
DR InterPro; IPR011035; Ribosomal_L25/Gln-tRNA_synth.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR009068; S15_NS1_RNA-bd.
DR InterPro; IPR000738; WHEP-TRS_dom.
DR PANTHER; PTHR43382; PTHR43382; 1.
DR Pfam; PF00043; GST_C; 1.
DR Pfam; PF03129; HGTP_anticodon; 1.
DR Pfam; PF09180; ProRS-C_1; 1.
DR Pfam; PF00749; tRNA-synt_1c; 1.
DR Pfam; PF03950; tRNA-synt_1c_C; 1.
DR Pfam; PF00587; tRNA-synt_2b; 1.
DR Pfam; PF00458; WHEP-TRS; 3.
DR PRINTS; PR00987; TRNASYNTHGLU.
DR SMART; SM00946; ProRS-C_1; 1.
DR SMART; SM00991; WHEP-TRS; 3.
DR SUPFAM; SSF47060; SSF47060; 3.
DR SUPFAM; SSF47616; SSF47616; 1.
DR SUPFAM; SSF50715; SSF50715; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR SUPFAM; SSF64586; SSF64586; 1.
DR TIGRFAMs; TIGR00463; gltX_arch; 1.
DR TIGRFAMs; TIGR00408; proS_fam_I; 1.
DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
DR PROSITE; PS00762; WHEP_TRS_1; 3.
DR PROSITE; PS51185; WHEP_TRS_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Aminoacyl-tRNA synthetase; ATP-binding;
KW Cytoplasm; Disease variant; Leukodystrophy; Ligase; Membrane;
KW Metal-binding; Methylation; Multifunctional enzyme; Neurodegeneration;
KW Nucleotide-binding; Phosphoprotein; Protein biosynthesis;
KW Reference proteome; Repeat; RNA-binding; Translation regulation; Zinc.
FT CHAIN 1..1512
FT /note="Bifunctional glutamate/proline--tRNA ligase"
FT /id="PRO_0000119743"
FT DOMAIN 749..805
FT /note="WHEP-TRS 1"
FT DOMAIN 822..878
FT /note="WHEP-TRS 2"
FT DOMAIN 900..956
FT /note="WHEP-TRS 3"
FT REGION 164..759
FT /note="Glutamate--tRNA ligase"
FT REGION 709..744
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 760..956
FT /note="3 X 57 AA approximate repeats"
FT REGION 869..900
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 956..1012
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 959..991
FT /note="Charged"
FT REGION 1007..1512
FT /note="Proline--tRNA ligase"
FT MOTIF 204..214
FT /note="'HIGH' region"
FT MOTIF 432..436
FT /note="'KMSKS' region"
FT COMPBIAS 710..729
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 730..744
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 875..893
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 956..987
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 988..1006
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 211
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 398
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 432..436
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 1121..1123
FT /ligand="L-proline"
FT /ligand_id="ChEBI:CHEBI:60039"
FT /evidence="ECO:0000269|PubMed:24100331,
FT ECO:0007744|PDB:4K87"
FT BINDING 1152..1154
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23263184,
FT ECO:0000269|PubMed:24100331, ECO:0007744|PDB:4HVC,
FT ECO:0007744|PDB:4K87"
FT BINDING 1152
FT /ligand="L-proline"
FT /ligand_id="ChEBI:CHEBI:60039"
FT /evidence="ECO:0000269|PubMed:24100331,
FT ECO:0007744|PDB:4K87"
FT BINDING 1163..1164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23263184,
FT ECO:0000269|PubMed:24100331, ECO:0007744|PDB:4HVC,
FT ECO:0007744|PDB:4K87"
FT BINDING 1237..1240
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23263184,
FT ECO:0000269|PubMed:24100331, ECO:0007744|PDB:4HVC,
FT ECO:0007744|PDB:4K87"
FT BINDING 1242
FT /ligand="L-proline"
FT /ligand_id="ChEBI:CHEBI:60039"
FT /evidence="ECO:0000269|PubMed:24100331,
FT ECO:0007744|PDB:4K87"
FT BINDING 1276
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23263184,
FT ECO:0000269|PubMed:24100331, ECO:0007744|PDB:4HVC,
FT ECO:0007744|PDB:4K87"
FT BINDING 1448
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23263184,
FT ECO:0000269|PubMed:24100331, ECO:0007744|PDB:4HVC,
FT ECO:0007744|PDB:4K86, ECO:0007744|PDB:4K87"
FT BINDING 1453
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23263184,
FT ECO:0000269|PubMed:24100331, ECO:0007744|PDB:4HVC,
FT ECO:0007744|PDB:4K86, ECO:0007744|PDB:4K87,
FT ECO:0007744|PDB:4K88"
FT BINDING 1495
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23263184,
FT ECO:0000269|PubMed:24100331, ECO:0007744|PDB:4HVC,
FT ECO:0007744|PDB:4K86, ECO:0007744|PDB:4K87,
FT ECO:0007744|PDB:4K88"
FT BINDING 1497
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23263184,
FT ECO:0000269|PubMed:24100331, ECO:0007744|PDB:4HVC,
FT ECO:0007744|PDB:4K86, ECO:0007744|PDB:4K87,
FT ECO:0007744|PDB:4K88"
FT MOD_RES 300
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 300
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:21908771"
FT MOD_RES 355
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 417
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 498
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 535
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 542
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 637
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 747
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 788
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 861
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8CGC7"
FT MOD_RES 872
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 882
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 885
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 886
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:19647514,
FT ECO:0000269|PubMed:21220307, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 891
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 898
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 998
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 999
FT /note="Phosphoserine; by RPS6KB1"
FT /evidence="ECO:0000269|PubMed:19647514,
FT ECO:0000269|PubMed:28178239"
FT MOD_RES 1000
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1152
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 1350
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1503
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VARIANT 296
FT /note="A -> P (in dbSNP:rs35999099)"
FT /id="VAR_037288"
FT VARIANT 308
FT /note="D -> E (in dbSNP:rs2230301)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005, ECO:0000269|PubMed:1988429,
FT ECO:0000269|PubMed:3290852, ECO:0000269|Ref.5"
FT /id="VAR_037289"
FT VARIANT 334
FT /note="Q -> H (in dbSNP:rs1063236)"
FT /evidence="ECO:0000269|PubMed:1988429,
FT ECO:0000269|PubMed:3290852, ECO:0000269|Ref.5"
FT /id="VAR_037290"
FT VARIANT 339..1512
FT /note="Missing (in HLD15)"
FT /evidence="ECO:0000269|PubMed:29576217"
FT /id="VAR_080800"
FT VARIANT 893
FT /note="P -> H (in dbSNP:rs5030751)"
FT /id="VAR_037291"
FT VARIANT 913
FT /note="E -> G (in dbSNP:rs2230302)"
FT /id="VAR_057358"
FT VARIANT 1043
FT /note="I -> V (in dbSNP:rs5030752)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_037292"
FT VARIANT 1107
FT /note="S -> F (in dbSNP:rs12144752)"
FT /id="VAR_037293"
FT VARIANT 1115
FT /note="P -> R (in HLD15; slightly decreased protein level;
FT does not affect multisynthetase complex assembly;
FT dbSNP:rs1288116010)"
FT /evidence="ECO:0000269|PubMed:29576217"
FT /id="VAR_080801"
FT VARIANT 1126
FT /note="M -> T (in HLD15; unknown pathological significance;
FT small decrease in aminoacylation activity;
FT dbSNP:rs1474000585)"
FT /evidence="ECO:0000269|PubMed:29576217"
FT /id="VAR_080802"
FT VARIANT 1160
FT /note="P -> S (in HLD15; unknown pathological significance;
FT dbSNP:rs898824971)"
FT /evidence="ECO:0000269|PubMed:29576217"
FT /id="VAR_080803"
FT VARIANT 1399
FT /note="T -> N (in dbSNP:rs34559775)"
FT /id="VAR_037294"
FT MUTAGEN 886
FT /note="S->A: Abolishes release from the aminoacyl-tRNA
FT synthetase multienzyme complex and association with the
FT GAIT complex upon interferon-gamma treatment. Abolishes
FT interaction with SYNCRIP."
FT /evidence="ECO:0000269|PubMed:23071094"
FT MUTAGEN 886
FT /note="S->D: Not active in translation inhibition
FT (phosphomimetic) and abolishes GAIT complex association
FT with eiF4G. No effect on interaction with SYNCRIP."
FT /evidence="ECO:0000269|PubMed:23071094"
FT MUTAGEN 999
FT /note="S->A: Not active in translation inhibition,
FT abolishes release from the aminoacyl-tRNA synthetase
FT multienzyme complex and association with the GAIT complex
FT upon interferon-gamma treatment."
FT /evidence="ECO:0000269|PubMed:23071094"
FT MUTAGEN 999
FT /note="S->D: Active in translation inhibition
FT (phosphomimetic). No effect on GAIT complex association
FT with eiF4G."
FT /evidence="ECO:0000269|PubMed:23071094"
FT MUTAGEN 1097
FT /note="F->A: Almost complete loss of prolyl-tRNA ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:24100331"
FT MUTAGEN 1097
FT /note="F->W: No effect on prolyl-tRNA ligase activity.
FT Decreases inhibition by halofuginone."
FT /evidence="ECO:0000269|PubMed:24100331"
FT MUTAGEN 1152
FT /note="R->K: No effect on prolyl-tRNA ligase activity.
FT Decreases inhibition by halofuginone."
FT /evidence="ECO:0000269|PubMed:24100331"
FT MUTAGEN 1152
FT /note="R->L: Almost complete loss of prolyl-tRNA ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:24100331"
FT CONFLICT 532
FT /note="K -> R (in Ref. 1; CAI45949)"
FT /evidence="ECO:0000305"
FT CONFLICT 594
FT /note="L -> F (in Ref. 4; CAA38224 and 5; AAS72877)"
FT /evidence="ECO:0000305"
FT CONFLICT 943
FT /note="K -> E (in Ref. 1; CAI45949)"
FT /evidence="ECO:0000305"
FT CONFLICT 1177..1179
FT /note="ATM -> VTV (in Ref. 1; CAI45949)"
FT /evidence="ECO:0000305"
FT CONFLICT 1441
FT /note="K -> R (in Ref. 1; CAI45949)"
FT /evidence="ECO:0000305"
FT STRAND 4..7
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 10..12
FT /evidence="ECO:0007829|PDB:5A34"
FT HELIX 15..24
FT /evidence="ECO:0007829|PDB:5A1N"
FT TURN 25..27
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 51..61
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 72..87
FT /evidence="ECO:0007829|PDB:5A1N"
FT TURN 88..90
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 95..106
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:5A1N"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:5BMU"
FT HELIX 119..129
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 132..139
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 145..155
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 158..167
FT /evidence="ECO:0007829|PDB:5A1N"
FT HELIX 750..769
FT /evidence="ECO:0007829|PDB:1FYJ"
FT HELIX 774..795
FT /evidence="ECO:0007829|PDB:1FYJ"
FT TURN 1020..1022
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1024..1034
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1038..1040
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1042..1045
FT /evidence="ECO:0007829|PDB:4K86"
FT STRAND 1047..1049
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1051..1070
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1080..1083
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1084..1087
FT /evidence="ECO:0007829|PDB:4HVC"
FT TURN 1088..1090
FT /evidence="ECO:0007829|PDB:4K86"
FT HELIX 1095..1100
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1102..1107
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1110..1118
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1120..1122
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1123..1133
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1137..1139
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1142..1151
FT /evidence="ECO:0007829|PDB:4HVC"
FT TURN 1160..1162
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1165..1178
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1179..1198
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1206..1209
FT /evidence="ECO:0007829|PDB:4HVC"
FT TURN 1212..1214
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1219..1229
FT /evidence="ECO:0007829|PDB:4HVC"
FT TURN 1230..1233
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1234..1245
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1247..1252
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1255..1257
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1261..1263
FT /evidence="ECO:0007829|PDB:7BBU"
FT STRAND 1265..1267
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1269..1276
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1278..1287
FT /evidence="ECO:0007829|PDB:4HVC"
FT TURN 1297..1299
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1303..1308
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1313..1315
FT /evidence="ECO:0007829|PDB:4K87"
FT HELIX 1317..1336
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1341..1343
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1347..1349
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1351..1360
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1364..1369
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1371..1376
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1378..1383
FT /evidence="ECO:0007829|PDB:4HVC"
FT TURN 1384..1386
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1389..1393
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1394..1396
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1397..1423
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1424..1426
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1430..1438
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1442..1447
FT /evidence="ECO:0007829|PDB:4HVC"
FT HELIX 1451..1462
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1477..1484
FT /evidence="ECO:0007829|PDB:4HVC"
FT STRAND 1498..1501
FT /evidence="ECO:0007829|PDB:7BBU"
FT STRAND 1504..1509
FT /evidence="ECO:0007829|PDB:4HVC"
SQ SEQUENCE 1512 AA; 170591 MW; 2CE4311076719403 CRC64;
MATLSLTVNS GDPPLGALLA VEHVKDDVSI SVEEGKENIL HVSENVIFTD VNSILRYLAR
VATTAGLYGS NLMEHTEIDH WLEFSATKLS SCDSFTSTIN ELNHCLSLRT YLVGNSLSLA
DLCVWATLKG NAAWQEQLKQ KKAPVHVKRW FGFLEAQQAF QSVGTKWDVS TTKARVAPEK
KQDVGKFVEL PGAEMGKVTV RFPPEASGYL HIGHAKAALL NQHYQVNFKG KLIMRFDDTN
PEKEKEDFEK VILEDVAMLH IKPDQFTYTS DHFETIMKYA EKLIQEGKAY VDDTPAEQMK
AEREQRIDSK HRKNPIEKNL QMWEEMKKGS QFGQSCCLRA KIDMSSNNGC MRDPTLYRCK
IQPHPRTGNK YNVYPTYDFA CPIVDSIEGV THALRTTEYH DRDEQFYWII EALGIRKPYI
WEYSRLNLNN TVLSKRKLTW FVNEGLVDGW DDPRFPTVRG VLRRGMTVEG LKQFIAAQGS
SRSVVNMEWD KIWAFNKKVI DPVAPRYVAL LKKEVIPVNV PEAQEEMKEV AKHPKNPEVG
LKPVWYSPKV FIEGADAETF SEGEMVTFIN WGNLNITKIH KNADGKIISL DAKLNLENKD
YKKTTKVTWL AETTHALPIP VICVTYEHLI TKPVLGKDED FKQYVNKNSK HEELMLGDPC
LKDLKKGDII QLQRRGFFIC DQPYEPVSPY SCKEAPCVLI YIPDGHTKEM PTSGSKEKTK
VEATKNETSA PFKERPTPSL NNNCTTSEDS LVLYNRVAVQ GDVVRELKAK KAPKEDVDAA
VKQLLSLKAE YKEKTGQEYK PGNPPAEIGQ NISSNSSASI LESKSLYDEV AAQGEVVRKL
KAEKSPKAKI NEAVECLLSL KAQYKEKTGK EYIPGQPPLS QSSDSSPTRN SEPAGLETPE
AKVLFDKVAS QGEVVRKLKT EKAPKDQVDI AVQELLQLKA QYKSLIGVEY KPVSATGAED
KDKKKKEKEN KSEKQNKPQK QNDGQRKDPS KNQGGGLSSS GAGEGQGPKK QTRLGLEAKK
EENLADWYSQ VITKSEMIEY HDISGCYILR PWAYAIWEAI KDFFDAEIKK LGVENCYFPM
FVSQSALEKE KTHVADFAPE VAWVTRSGKT ELAEPIAIRP TSETVMYPAY AKWVQSHRDL
PIKLNQWCNV VRWEFKHPQP FLRTREFLWQ EGHSAFATME EAAEEVLQIL DLYAQVYEEL
LAIPVVKGRK TEKEKFAGGD YTTTIEAFIS ASGRAIQGGT SHHLGQNFSK MFEIVFEDPK
IPGEKQFAYQ NSWGLTTRTI GVMTMVHGDN MGLVLPPRVA CVQVVIIPCG ITNALSEEDK
EALIAKCNDY RRRLLSVNIR VRADLRDNYS PGWKFNHWEL KGVPIRLEVG PRDMKSCQFV
AVRRDTGEKL TVAENEAETK LQAILEDIQV TLFTRASEDL KTHMVVANTM EDFQKILDSG
KIVQIPFCGE IDCEDWIKKT TARDQDLEPG APSMGAKSLC IPFKPLCELQ PGAKCVCGKN
PAKYYTLFGR SY
