ID SYVC_HUMAN Reviewed; 1264 AA. AC P26640; B0V1N1; B4DZ61; Q5JQ90; Q96E77; Q9UQM2; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 4. DT 28-JUN-2023, entry version 230. DE RecName: Full=Valine--tRNA ligase {ECO:0000305}; DE EC=6.1.1.9 {ECO:0000269|PubMed:8428657}; DE AltName: Full=Protein G7a; DE AltName: Full=Valyl-tRNA synthetase; DE Short=ValRS; GN Name=VARS1 {ECO:0000312|HGNC:HGNC:12651}; Synonyms=G7A, VARS, VARS2; 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 [MRNA] (ISOFORM 1). RX PubMed=1898367; DOI=10.1042/bj2780809; RA Hsieh H.-L., Campbell R.D.; RT "Evidence that gene G7a in the human major histocompatibility complex RT encodes valyl-tRNA synthetase."; RL Biochem. J. 278:809-816(1991). RN [2] RP ERRATUM OF PUBMED:1898367. RA Hsieh S.-L., Campbell R.D.; RL Biochem. J. 281:879-879(1992). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14656967; DOI=10.1101/gr.1736803; RA Xie T., Rowen L., Aguado B., Ahearn M.E., Madan A., Qin S., Campbell R.D., RA Hood L.; RT "Analysis of the gene-dense major histocompatibility complex class III RT region and its comparison to mouse."; RL Genome Res. 13:2621-2636(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Shiina S., Tamiya G., Oka A., Inoko H.; RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [7] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle; 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 [9] RP PROTEIN SEQUENCE OF 2-17; 123-147; 451-461; 592-606; 619-633; 935-942; RP 1120-1129 AND 1252-1262, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT RP SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Hepatoma; RA Bienvenut W.V., Dhillon A.S., Kolch W.; RL Submitted (FEB-2008) to UniProtKB. RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 201-1263 (ISOFORM 1), FUNCTION, AND CATALYTIC RP ACTIVITY. RX PubMed=8428657; DOI=10.1016/0378-1119(93)90122-j; RA Vilalta A., Donovan D., Wood L., Vogeli G., Yang D.C.H.; RT "Cloning, sequencing and expression of a cDNA encoding mammalian valyl-tRNA RT synthetase."; RL Gene 123:181-186(1993). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-645, 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 [12] 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 [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-437 AND SER-527, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [16] 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 [17] 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 [18] RP INVOLVEMENT IN NDMSCA, AND VARIANTS NDMSCA PHE-885 AND GLN-1058. RX PubMed=26539891; DOI=10.1016/j.neuron.2015.09.048; RA Karaca E., Harel T., Pehlivan D., Jhangiani S.N., Gambin T., RA Coban Akdemir Z., Gonzaga-Jauregui C., Erdin S., Bayram Y., Campbell I.M., RA Hunter J.V., Atik M.M., Van Esch H., Yuan B., Wiszniewski W., Isikay S., RA Yesil G., Yuregir O.O., Tug Bozdogan S., Aslan H., Aydin H., Tos T., RA Aksoy A., De Vivo D.C., Jain P., Geckinli B.B., Sezer O., Gul D., RA Durmaz B., Cogulu O., Ozkinay F., Topcu V., Candan S., Cebi A.H., Ikbal M., RA Yilmaz Gulec E., Gezdirici A., Koparir E., Ekici F., Coskun S., Cicek S., RA Karaer K., Koparir A., Duz M.B., Kirat E., Fenercioglu E., Ulucan H., RA Seven M., Guran T., Elcioglu N., Yildirim M.S., Aktas D., Alikasifoglu M., RA Ture M., Yakut T., Overton J.D., Yuksel A., Ozen M., Muzny D.M., RA Adams D.R., Boerwinkle E., Chung W.K., Gibbs R.A., Lupski J.R.; RT "Genes that affect brain structure and function identified by rare variant RT analyses of mendelian neurologic disease."; RL Neuron 88:499-513(2015). CC -!- FUNCTION: Catalyzes the attachment of valine to tRNA(Val). CC {ECO:0000269|PubMed:8428657}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-valine + tRNA(Val) = AMP + diphosphate + L-valyl- CC tRNA(Val); Xref=Rhea:RHEA:10704, Rhea:RHEA-COMP:9672, Rhea:RHEA- CC COMP:9708, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57762, CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78537, ChEBI:CHEBI:456215; EC=6.1.1.9; CC Evidence={ECO:0000269|PubMed:8428657}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10705; CC Evidence={ECO:0000305|PubMed:8428657}; CC -!- ACTIVITY REGULATION: Can be regulated by protein kinase C-dependent CC phosphorylation. CC -!- SUBUNIT: Forms high-molecular-mass aggregates with elongation factor 1. CC -!- INTERACTION: CC P26640; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-355765, EBI-739580; CC P26640; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-355765, EBI-1383687; CC P26640; Q13554-3: CAMK2B; NbExp=3; IntAct=EBI-355765, EBI-11523526; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P26640-1; Sequence=Displayed; CC Name=2; CC IsoId=P26640-2; Sequence=VSP_056480, VSP_056481, VSP_056482; CC -!- DISEASE: Neurodevelopmental disorder with microcephaly, seizures, and CC cortical atrophy (NDMSCA) [MIM:617802]: An autosomal recessive CC neurodevelopmental disorder characterized by severe developmental CC delay, intellectual disability, severe microcephaly, and cortical CC atrophy. {ECO:0000269|PubMed:26539891}. Note=The disease may be caused CC by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA41990.1; Type=Frameshift; Evidence={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; X59303; CAA41990.1; ALT_FRAME; mRNA. DR EMBL; AF134726; AAD21819.1; -; Genomic_DNA. DR EMBL; BA000025; BAB63303.1; -; Genomic_DNA. DR EMBL; AK302762; BAG63973.1; -; mRNA. DR EMBL; AL662834; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL662899; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL671762; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR925765; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471081; EAX03523.1; -; Genomic_DNA. DR EMBL; BC012808; AAH12808.1; -; mRNA. DR EMBL; M98326; AAA81332.1; -; mRNA. DR CCDS; CCDS34412.1; -. [P26640-1] DR PIR; S17675; S17675. DR RefSeq; NP_006286.1; NM_006295.2. [P26640-1] DR AlphaFoldDB; P26640; -. DR SMR; P26640; -. DR BioGRID; 113250; 234. DR IntAct; P26640; 72. DR MINT; P26640; -. DR STRING; 9606.ENSP00000364815; -. DR BindingDB; P26640; -. DR ChEMBL; CHEMBL2612; -. DR DrugBank; DB00161; Valine. DR GlyGen; P26640; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P26640; -. DR MetOSite; P26640; -. DR PhosphoSitePlus; P26640; -. DR SwissPalm; P26640; -. DR BioMuta; VARS; -. DR DMDM; 12644177; -. DR CPTAC; CPTAC-1642; -. DR EPD; P26640; -. DR jPOST; P26640; -. DR MassIVE; P26640; -. DR MaxQB; P26640; -. DR PaxDb; P26640; -. DR PeptideAtlas; P26640; -. DR ProteomicsDB; 54358; -. [P26640-1] DR ProteomicsDB; 5573; -. DR Antibodypedia; 51277; 226 antibodies from 28 providers. DR DNASU; 7407; -. DR Ensembl; ENST00000211402.10; ENSP00000211402.6; ENSG00000096171.14. [P26640-1] DR Ensembl; ENST00000375663.8; ENSP00000364815.3; ENSG00000204394.13. [P26640-1] DR Ensembl; ENST00000422694.6; ENSP00000401121.2; ENSG00000224264.9. DR Ensembl; ENST00000435657.6; ENSP00000415316.2; ENSG00000231116.9. DR Ensembl; ENST00000457796.6; ENSP00000403359.2; ENSG00000226589.9. [P26640-1] DR GeneID; 7407; -. DR KEGG; hsa:7407; -. DR MANE-Select; ENST00000375663.8; ENSP00000364815.3; NM_006295.3; NP_006286.1. DR UCSC; uc003nxe.4; human. [P26640-1] DR AGR; HGNC:12651; -. DR CTD; 7407; -. DR DisGeNET; 7407; -. DR GeneCards; VARS1; -. DR HGNC; HGNC:12651; VARS1. DR HPA; ENSG00000204394; Low tissue specificity. DR MalaCards; VARS1; -. DR MIM; 192150; gene. DR MIM; 617802; phenotype. DR neXtProt; NX_P26640; -. DR OpenTargets; ENSG00000204394; -. DR Orphanet; 420728; Combined oxidative phosphorylation defect type 20. DR PharmGKB; PA37275; -. DR VEuPathDB; HostDB:ENSG00000204394; -. DR eggNOG; KOG0432; Eukaryota. DR eggNOG; KOG0867; Eukaryota. DR GeneTree; ENSGT00940000157775; -. DR HOGENOM; CLU_001493_0_1_1; -. DR InParanoid; P26640; -. DR OMA; FATKLWN; -. DR OrthoDB; 5473263at2759; -. DR PhylomeDB; P26640; -. DR TreeFam; TF300648; -. DR BRENDA; 6.1.1.9; 2681. DR PathwayCommons; P26640; -. DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation. DR SignaLink; P26640; -. DR SIGNOR; P26640; -. DR BioGRID-ORCS; 7407; 829 hits in 1128 CRISPR screens. DR ChiTaRS; VARS; human. DR GeneWiki; VARS; -. DR GenomeRNAi; 7407; -. DR Pharos; P26640; Tchem. DR PRO; PR:P26640; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; P26640; protein. DR Bgee; ENSG00000096171; Expressed in medulla oblongata and 11 other tissues. DR ExpressionAtlas; P26640; baseline and differential. DR Genevisible; P26640; HS. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0002161; F:aminoacyl-tRNA editing activity; IEA:InterPro. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004832; F:valine-tRNA ligase activity; IDA:UniProtKB. DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome. DR GO; GO:0006438; P:valyl-tRNA aminoacylation; IBA:GO_Central. DR CDD; cd07962; Anticodon_Ia_Val; 1. DR CDD; cd10294; GST_C_ValRS_N; 1. DR CDD; cd00817; ValRS_core; 1. DR Gene3D; 1.20.1050.10; -; 1. DR Gene3D; 3.40.50.620; HUPs; 2. DR Gene3D; 1.10.287.380; Valyl-tRNA synthetase, C-terminal domain; 1. DR Gene3D; 3.90.740.10; Valyl/Leucyl/Isoleucyl-tRNA synthetase, editing domain; 1. DR HAMAP; MF_02004; Val_tRNA_synth_type1; 1. DR InterPro; IPR001412; aa-tRNA-synth_I_CS. DR InterPro; IPR002300; aa-tRNA-synth_Ia. DR InterPro; IPR033705; Anticodon_Ia_Val. DR InterPro; IPR010987; Glutathione-S-Trfase_C-like. DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf. DR InterPro; IPR004046; GST_C. DR InterPro; IPR013155; M/V/L/I-tRNA-synth_anticd-bd. DR InterPro; IPR014729; Rossmann-like_a/b/a_fold. DR InterPro; IPR009080; tRNAsynth_Ia_anticodon-bd. DR InterPro; IPR037118; Val-tRNA_synth_C_sf. DR InterPro; IPR009008; Val/Leu/Ile-tRNA-synth_edit. DR InterPro; IPR002303; Valyl-tRNA_ligase. DR PANTHER; PTHR11946:SF115; VALINE--TRNA LIGASE; 1. DR PANTHER; PTHR11946; VALYL-TRNA SYNTHETASES; 1. DR Pfam; PF08264; Anticodon_1; 1. DR Pfam; PF00043; GST_C; 1. DR Pfam; PF00133; tRNA-synt_1; 1. DR PRINTS; PR00986; TRNASYNTHVAL. DR SUPFAM; SSF47323; Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases; 1. DR SUPFAM; SSF47616; GST C-terminal domain-like; 1. DR SUPFAM; SSF52374; Nucleotidylyl transferase; 1. DR SUPFAM; SSF50677; ValRS/IleRS/LeuRS editing domain; 1. DR TIGRFAMs; TIGR00422; valS; 1. DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 1. DR PROSITE; PS50405; GST_CTER; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding; KW Direct protein sequencing; Disease variant; Epilepsy; KW Intellectual disability; Ligase; Nucleotide-binding; Phosphoprotein; KW Protein biosynthesis; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..1264 FT /note="Valine--tRNA ligase" FT /id="PRO_0000106253" FT DOMAIN 89..219 FT /note="GST C-terminal" FT REGION 217..296 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 344..354 FT /note="'HIGH' region" FT MOTIF 862..866 FT /note="'KMSKS' region" FT COMPBIAS 233..249 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 262..277 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 865 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|Ref.9, ECO:0007744|PubMed:22223895, FT ECO:0007744|PubMed:22814378" FT MOD_RES 437 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 527 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 645 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 1..295 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056480" FT VAR_SEQ 589..592 FT /note="AVKI -> PAQV (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056481" FT VAR_SEQ 593..1264 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056482" FT VARIANT 51 FT /note="P -> R (in dbSNP:rs2607015)" FT /id="VAR_052647" FT VARIANT 51 FT /note="P -> T (in dbSNP:rs2753960)" FT /id="VAR_061909" FT VARIANT 181 FT /note="R -> C (in dbSNP:rs35196751)" FT /id="VAR_052648" FT VARIANT 626 FT /note="P -> S (in dbSNP:rs11531)" FT /id="VAR_052649" FT VARIANT 885 FT /note="L -> F (in NDMSCA; unknown pathological FT significance; dbSNP:rs1060499734)" FT /evidence="ECO:0000269|PubMed:26539891" FT /id="VAR_080602" FT VARIANT 1008 FT /note="P -> L (in dbSNP:rs1076827)" FT /id="VAR_052650" FT VARIANT 1058 FT /note="R -> Q (in NDMSCA; unknown pathological FT significance; dbSNP:rs769369302)" FT /evidence="ECO:0000269|PubMed:26539891" FT /id="VAR_080603" FT CONFLICT 51 FT /note="P -> S (in Ref. 1; CAA41990 and 7; AAH12808)" FT /evidence="ECO:0000305" FT CONFLICT 331 FT /note="A -> G (in Ref. 10; AAA81332)" FT /evidence="ECO:0000305" FT CONFLICT 590 FT /note="V -> G (in Ref. 1; CAA41990)" FT /evidence="ECO:0000305" FT CONFLICT 792 FT /note="S -> F (in Ref. 1; CAA41990)" FT /evidence="ECO:0000305" FT CONFLICT 1064 FT /note="M -> I (in Ref. 10; AAA81332)" FT /evidence="ECO:0000305" FT CONFLICT 1169 FT /note="Missing (in Ref. 10; AAA81332)" FT /evidence="ECO:0000305" SQ SEQUENCE 1264 AA; 140476 MW; 95CCDDBB3AB148AD CRC64; MSTLYVSPHP DAFPSLRALI AARYGEAGEG PGWGGAHPRI CLQPPPTSRT PFPPPRLPAL EQGPGGLWVW GATAVAQLLW PAGLGGPGGS RAAVLVQQWV SYADTELIPA ACGATLPALG LRSSAQDPQA VLGALGRALS PLEEWLRLHT YLAGEAPTLA DLAAVTALLL PFRYVLDPPA RRIWNNVTRW FVTCVRQPEF RAVLGEVVLY SGARPLSHQP GPEAPALPKT AAQLKKEAKK REKLEKFQQK QKIQQQQPPP GEKKPKPEKR EKRDPGVITY DLPTPPGEKK DVSGPMPDSY SPRYVEAAWY PWWEQQGFFK PEYGRPNVSA ANPRGVFMMC IPPPNVTGSL HLGHALTNAI QDSLTRWHRM RGETTLWNPG CDHAGIATQV VVEKKLWREQ GLSRHQLGRE AFLQEVWKWK EEKGDRIYHQ LKKLGSSLDW DRACFTMDPK LSAAVTEAFV RLHEEGIIYR STRLVNWSCT LNSAISDIEV DKKELTGRTL LSVPGYKEKV EFGVLVSFAY KVQGSDSDEE VVVATTRIET MLGDVAVAVH PKDTRYQHLK GKNVIHPFLS RSLPIVFDEF VDMDFGTGAV KITPAHDQND YEVGQRHGLE AISIMDSRGA LINVPPPFLG LPRFEARKAV LVALKERGLF RGIEDNPMVV PLCNRSKDVV EPLLRPQWYV RCGEMAQAAS AAVTRGDLRI LPEAHQRTWH AWMDNIREWC ISRQLWWGHR IPAYFVTVSD PAVPPGEDPD GRYWVSGRNE AEAREKAAKE FGVSPDKISL QQDEDVLDTW FSSGLFPLSI LGWPNQSEDL SVFYPGTLLE TGHDILFFWV ARMVMLGLKL TGRLPFREVY LHAIVRDAHG RKMSKSLGNV IDPLDVIYGI SLQGLHNQLL NSNLDPSEVE KAKEGQKADF PAGIPECGTD ALRFGLCAYM SQGRDINLDV NRILGYRHFC NKLWNATKFA LRGLGKGFVP SPTSQPGGHE SLVDRWIRSR LTEAVRLSNQ GFQAYDFPAV TTAQYSFWLY ELCDVYLECL KPVLNGVDQV AAECARQTLY TCLDVGLRLL SPFMPFVTEE LFQRLPRRMP QAPPSLCVTP YPEPSECSWK DPEAEAALEL ALSITRAVRS LRADYNLTRI RPDCFLEVAD EATGALASAV SGYVQALASA GVVAVLALGA PAPQGCAVAL ASDRCSIHLQ LQGLVDPARE LGKLQAKRVE AQRQAQRLRE RRAASGYPVK VPLEVQEADE AKLQQTEAEL RKVDEAIALF QKML //