ID SYEM_HUMAN Reviewed; 523 AA. AC Q5JPH6; B3KTT2; D3DWF1; Q86YH3; Q8TF31; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 31-OCT-2006, sequence version 2. DT 27-MAR-2024, entry version 154. DE RecName: Full=Nondiscriminating glutamyl-tRNA synthetase EARS2, mitochondrial {ECO:0000305}; DE EC=6.1.1.24 {ECO:0000269|PubMed:19805282}; DE AltName: Full=Glutamate--tRNA(Gln) ligase EARS2, mitochondrial {ECO:0000305}; DE EC=6.1.1.17 {ECO:0000269|PubMed:19805282}; DE AltName: Full=Glutamyl-tRNA synthetase; DE Short=GluRS; DE AltName: Full=Mitochondrial glutamyl-tRNA synthetase {ECO:0000303|PubMed:19805282}; DE Short=mtGluRS {ECO:0000303|PubMed:19805282}; DE Flags: Precursor; GN Name=EARS2 {ECO:0000312|HGNC:HGNC:29419}; GN Synonyms=KIAA1970 {ECO:0000303|PubMed:11853319}; 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] (ISOFORM 1), AND VARIANT GLY-457. RC TISSUE=Kidney; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-457. RC TISSUE=Testis; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLY-457. RC TISSUE=Brain; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-523 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=11853319; DOI=10.1093/dnares/8.6.319; RA Nagase T., Kikuno R., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XXII. The RT complete sequences of 50 new cDNA clones which code for large proteins."; RL DNA Res. 8:319-327(2001). RN [6] RP IDENTIFICATION. RX PubMed=15779907; DOI=10.1021/bi047527z; RA Bonnefond L., Fender A., Rudinger-Thirion J., Giege R., Florentz C., RA Sissler M.; RT "Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: RT characterization of AspRS and TyrRS."; RL Biochemistry 44:4805-4816(2005). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP SUBCELLULAR LOCATION. RX PubMed=19805282; DOI=10.1073/pnas.0907602106; RA Nagao A., Suzuki T., Katoh T., Sakaguchi Y., Suzuki T.; RT "Biogenesis of glutaminyl-mt tRNAGln in human mitochondria."; RL Proc. Natl. Acad. Sci. U.S.A. 106:16209-16214(2009). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-486, 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 [9] 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 [10] 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 [11] 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 [12] RP VARIANTS COXPD12 HIS-55; LYS-96; HIS-107; TRP-108; SER-110; TYR-167; RP GLY-168; SER-204; SER-224; CYS-317; 426-THR-ARG-427 DELINS LEU AND GLN-516. RX PubMed=22492562; DOI=10.1093/brain/aws070; RA Steenweg M.E., Ghezzi D., Haack T., Abbink T.E., Martinelli D., RA van Berkel C.G., Bley A., Diogo L., Grillo E., Te Water Naude J., RA Strom T.M., Bertini E., Prokisch H., van der Knaap M.S., Zeviani M.; RT "Leukoencephalopathy with thalamus and brainstem involvement and high RT lactate 'LTBL' caused by EARS2 mutations."; RL Brain 135:1387-1394(2012). RN [13] RP VARIANT COXPD12 GLU-65. RX PubMed=23008233; DOI=10.1093/brain/aws197; RA Talim B., Pyle A., Griffin H., Topaloglu H., Tokatli A., Keogh M.J., RA Santibanez-Koref M., Chinnery P.F., Horvath R.; RT "Multisystem fatal infantile disease caused by a novel homozygous EARS2 RT mutation."; RL Brain 136:E228-E228(2013). RN [14] RP VARIANTS COXPD12 CYS-107 AND GLN-489. RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679; RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y., RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H., RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y., RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K., RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M., RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K., RA Ohtake A., Okazaki Y.; RT "A comprehensive genomic analysis reveals the genetic landscape of RT mitochondrial respiratory chain complex deficiencies."; RL PLoS Genet. 12:E1005679-E1005679(2016). CC -!- FUNCTION: Non-discriminating glutamyl-tRNA synthetase that catalyzes CC aminoacylation of both mitochondrial tRNA(Glu) and tRNA(Gln) and CC participates in RNA aminoacylation for mitochondrial protein CC translation (PubMed:19805282). Attachs glutamate to tRNA(Glu) or CC tRNA(Gln) in a two-step reaction: glutamate is first activated by ATP CC to form Glu-AMP and then transferred to the acceptor end of tRNA(Glu) CC or tRNA(Gln) (PubMed:19805282). In vitro, cytoplasmic tRNA(Gln) is CC slightly glutamylated, but with low activity (PubMed:19805282). CC {ECO:0000269|PubMed:19805282}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-glutamate + tRNA(Glx) = AMP + diphosphate + L- CC glutamyl-tRNA(Glx); Xref=Rhea:RHEA:18397, Rhea:RHEA-COMP:9713, CC Rhea:RHEA-COMP:9716, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:78442, ChEBI:CHEBI:78520, CC ChEBI:CHEBI:456215; EC=6.1.1.24; CC Evidence={ECO:0000269|PubMed:19805282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18398; CC Evidence={ECO:0000269|PubMed:19805282}; 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 Evidence={ECO:0000269|PubMed:19805282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23541; CC Evidence={ECO:0000269|PubMed:19805282}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-glutamate + tRNA(Gln) = AMP + diphosphate + L- CC glutamyl-tRNA(Gln); Xref=Rhea:RHEA:64612, Rhea:RHEA-COMP:9662, CC Rhea:RHEA-COMP:9684, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:78442, ChEBI:CHEBI:78520, CC ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:19805282}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64613; CC Evidence={ECO:0000269|PubMed:19805282}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.27 uM for tRNA(Glu) {ECO:0000269|PubMed:19805282}; CC KM=1.7 uM for tRNA(Gln) {ECO:0000269|PubMed:19805282}; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:19805282}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q5JPH6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5JPH6-2; Sequence=VSP_057203; CC -!- DISEASE: Combined oxidative phosphorylation deficiency 12 (COXPD12) CC [MIM:614924]: An autosomal recessive, mitochondrial, neurologic CC disorder characterized by onset in infancy of hypotonia and delayed CC psychomotor development, or early developmental regression, associated CC with T2-weighted hyperintensities in the deep cerebral white matter, CC brainstem, and cerebellar white matter. Serum lactate is increased due CC to a defect in mitochondrial respiration. There are 2 main phenotypic CC groups: those with a milder disease course and some recovery of skills CC after age 2 years, and those with a severe disease course resulting in CC marked disability. {ECO:0000269|PubMed:22492562, CC ECO:0000269|PubMed:23008233, ECO:0000269|PubMed:26741492}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family. CC Glutamate--tRNA ligase type 1 subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK095998; BAG53194.1; -; mRNA. DR EMBL; AL832489; CAI46121.1; -; mRNA. DR EMBL; CH471145; EAW55822.1; -; Genomic_DNA. DR EMBL; CH471145; EAW55824.1; -; Genomic_DNA. DR EMBL; BC040013; AAH40013.1; -; mRNA. DR EMBL; AB075850; BAB85556.1; -; mRNA. DR CCDS; CCDS42132.1; -. [Q5JPH6-1] DR CCDS; CCDS76844.1; -. [Q5JPH6-2] DR RefSeq; NP_001077083.1; NM_001083614.1. [Q5JPH6-1] DR RefSeq; NP_001295140.1; NM_001308211.1. [Q5JPH6-2] DR AlphaFoldDB; Q5JPH6; -. DR SMR; Q5JPH6; -. DR BioGRID; 125866; 149. DR IntAct; Q5JPH6; 9. DR MINT; Q5JPH6; -. DR STRING; 9606.ENSP00000456218; -. DR DrugBank; DB00142; Glutamic acid. DR iPTMnet; Q5JPH6; -. DR PhosphoSitePlus; Q5JPH6; -. DR SwissPalm; Q5JPH6; -. DR BioMuta; EARS2; -. DR DMDM; 117949790; -. DR EPD; Q5JPH6; -. DR jPOST; Q5JPH6; -. DR MassIVE; Q5JPH6; -. DR MaxQB; Q5JPH6; -. DR PaxDb; 9606-ENSP00000395196; -. DR PeptideAtlas; Q5JPH6; -. DR ProteomicsDB; 63015; -. [Q5JPH6-1] DR Pumba; Q5JPH6; -. DR Antibodypedia; 25969; 153 antibodies from 22 providers. DR DNASU; 124454; -. DR Ensembl; ENST00000449606.7; ENSP00000395196.2; ENSG00000103356.18. [Q5JPH6-1] DR Ensembl; ENST00000563232.1; ENSP00000456218.1; ENSG00000103356.18. [Q5JPH6-2] DR Ensembl; ENST00000674054.1; ENSP00000501251.1; ENSG00000103356.18. [Q5JPH6-1] DR GeneID; 124454; -. DR KEGG; hsa:124454; -. DR MANE-Select; ENST00000449606.7; ENSP00000395196.2; NM_001083614.2; NP_001077083.1. DR UCSC; uc002dlt.5; human. [Q5JPH6-1] DR AGR; HGNC:29419; -. DR CTD; 124454; -. DR DisGeNET; 124454; -. DR GeneCards; EARS2; -. DR HGNC; HGNC:29419; EARS2. DR HPA; ENSG00000103356; Low tissue specificity. DR MalaCards; EARS2; -. DR MIM; 612799; gene. DR MIM; 614924; phenotype. DR neXtProt; NX_Q5JPH6; -. DR OpenTargets; ENSG00000103356; -. DR Orphanet; 314051; Leukoencephalopathy-thalamus and brainstem anomalies-high lactate syndrome. DR PharmGKB; PA144596439; -. DR VEuPathDB; HostDB:ENSG00000103356; -. DR eggNOG; KOG1149; Eukaryota. DR GeneTree; ENSGT00390000009759; -. DR HOGENOM; CLU_015768_6_3_1; -. DR InParanoid; Q5JPH6; -. DR OMA; EAFKWVG; -. DR OrthoDB; 5404395at2759; -. DR PhylomeDB; Q5JPH6; -. DR TreeFam; TF313268; -. DR PathwayCommons; Q5JPH6; -. DR Reactome; R-HSA-379726; Mitochondrial tRNA aminoacylation. DR SignaLink; Q5JPH6; -. DR SIGNOR; Q5JPH6; -. DR BioGRID-ORCS; 124454; 383 hits in 1166 CRISPR screens. DR ChiTaRS; EARS2; human. DR GenomeRNAi; 124454; -. DR Pharos; Q5JPH6; Tbio. DR PRO; PR:Q5JPH6; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q5JPH6; Protein. DR Bgee; ENSG00000103356; Expressed in adrenal tissue and 164 other cell types or tissues. DR ExpressionAtlas; Q5JPH6; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004818; F:glutamate-tRNA ligase activity; IDA:UniProtKB. DR GO; GO:0050561; F:glutamate-tRNA(Gln) ligase activity; IDA:UniProtKB. DR GO; GO:0000049; F:tRNA binding; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006424; P:glutamyl-tRNA aminoacylation; IDA:UniProtKB. DR GO; GO:0070127; P:tRNA aminoacylation for mitochondrial protein translation; IDA:UniProtKB. DR CDD; cd00808; GluRS_core; 1. DR Gene3D; 1.10.10.350; -; 1. DR Gene3D; 3.40.50.620; HUPs; 1. DR HAMAP; MF_00022; Glu_tRNA_synth_type1; 1. DR InterPro; IPR045462; aa-tRNA-synth_I_cd-bd. DR InterPro; IPR020751; aa-tRNA-synth_I_codon-bd_sub2. DR InterPro; IPR001412; aa-tRNA-synth_I_CS. DR InterPro; IPR008925; aa_tRNA-synth_I_cd-bd_sf. DR InterPro; IPR004527; Glu-tRNA-ligase_bac/mito. DR InterPro; IPR000924; Glu/Gln-tRNA-synth. DR InterPro; IPR020058; Glu/Gln-tRNA-synth_Ib_cat-dom. DR InterPro; IPR033910; GluRS_core. DR InterPro; IPR014729; Rossmann-like_a/b/a_fold. DR NCBIfam; TIGR00464; gltX_bact; 1. DR PANTHER; PTHR43311; GLUTAMATE--TRNA LIGASE; 1. DR PANTHER; PTHR43311:SF2; GLUTAMATE--TRNA LIGASE, MITOCHONDRIAL-RELATED; 1. DR Pfam; PF19269; Anticodon_2; 1. DR Pfam; PF00749; tRNA-synt_1c; 1. DR PRINTS; PR00987; TRNASYNTHGLU. DR SUPFAM; SSF48163; An anticodon-binding domain of class I aminoacyl-tRNA synthetases; 1. DR SUPFAM; SSF52374; Nucleotidylyl transferase; 1. DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 1. DR Genevisible; Q5JPH6; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding; KW Disease variant; Ligase; Mitochondrion; Nucleotide-binding; KW Primary mitochondrial disease; Protein biosynthesis; Reference proteome; KW RNA-binding; Transit peptide. FT TRANSIT 1..41 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 42..523 FT /note="Nondiscriminating glutamyl-tRNA synthetase EARS2, FT mitochondrial" FT /id="PRO_0000254560" FT MOTIF 45..53 FT /note="'HIGH' region" FT MOTIF 284..288 FT /note="'KMSKS' region" FT BINDING 40..42 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 50 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 76 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 228..232 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 246 FT /ligand="L-glutamate" FT /ligand_id="ChEBI:CHEBI:29985" FT /evidence="ECO:0000250" FT BINDING 249 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT BINDING 284..288 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT MOD_RES 256 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9CXJ1" FT MOD_RES 486 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 497..523 FT /note="QGPPVAEMMLALGPKEVRERIQKVVSS -> VRQGHGLDCSLEPLIDPLNLH FT FLAGTELNIEYTKVNET (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_057203" FT VARIANT 55 FT /note="R -> H (in COXPD12; dbSNP:rs770862902)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069235" FT VARIANT 65 FT /note="K -> E (in COXPD12; dbSNP:rs397514595)" FT /evidence="ECO:0000269|PubMed:23008233" FT /id="VAR_069236" FT VARIANT 96 FT /note="E -> K (in COXPD12; dbSNP:rs397514593)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069237" FT VARIANT 107 FT /note="R -> C (in COXPD12; dbSNP:rs1355685453)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076183" FT VARIANT 107 FT /note="R -> H (in COXPD12; dbSNP:rs1021330566)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069238" FT VARIANT 108 FT /note="R -> W (in COXPD12; dbSNP:rs376103091)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069239" FT VARIANT 110 FT /note="G -> S (in COXPD12; dbSNP:rs201842633)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069240" FT VARIANT 167 FT /note="C -> Y (in COXPD12; dbSNP:rs397514594)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069241" FT VARIANT 168 FT /note="R -> G (in COXPD12; dbSNP:rs397514591)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069242" FT VARIANT 204 FT /note="G -> S (in COXPD12; dbSNP:rs397514592)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069243" FT VARIANT 224 FT /note="G -> S (in COXPD12; dbSNP:rs141129877)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069244" FT VARIANT 317 FT /note="G -> C (in COXPD12; dbSNP:rs746838793)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069245" FT VARIANT 426..427 FT /note="TR -> L (in COXPD12)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069246" FT VARIANT 457 FT /note="S -> G (in dbSNP:rs6497671)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005" FT /id="VAR_028840" FT VARIANT 489 FT /note="R -> Q (in COXPD12; dbSNP:rs757965573)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076184" FT VARIANT 516 FT /note="R -> Q (in COXPD12; dbSNP:rs201727231)" FT /evidence="ECO:0000269|PubMed:22492562" FT /id="VAR_069247" SQ SEQUENCE 523 AA; 58689 MW; FA9B19569AD9F5DB CRC64; MAALLRRLLQ RERPSAASGR PVGRREANLG TDAGVAVRVR FAPSPTGFLH LGGLRTALYN YIFAKKYQGS FILRLEDTDQ TRVVPGAAEN IEDMLEWAGI PPDESPRRGG PAGPYQQSQR LELYAQATEA LLKTGAAYPC FCSPQRLELL KKEALRNHQT PRYDNRCRNM SQEQVAQKLA KDPKPAIRFR LEQVVPAFQD LVYGWNRHEV ASVEGDPVIM KSDGFPTYHL ACVVDDHHMG ISHVLRGSEW LVSTAKHLLL YQALGWQPPH FAHLPLLLNR DGSKLSKRQG DVFLEHFAAD GFLPDSLLDI ITNCGSGFAE NQMGRTLPEL ITQFNLTQVT CHSALLDLEK LPEFNRLHLQ RLVSNESQRR QLVGKLQVLV EEAFGCQLQN RDVLNPVYVE RILLLRQGHI CRLQDLVSPV YSYLWTRPAV GRAQLDAISE KVDVIAKRVL GLLERSSMSL TQDMLNGELK KLSEGLEGTK YSNVMKLLRM ALSGQQQGPP VAEMMLALGP KEVRERIQKV VSS //