ID   SYIC_HUMAN              Reviewed;        1262 AA.
AC   P41252; A8KAE9; Q5TCD0; Q7Z3T4; Q9H588;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   16-JUN-2009, sequence version 2.
DT   27-MAR-2024, entry version 220.
DE   RecName: Full=Isoleucine--tRNA ligase, cytoplasmic;
DE            EC=6.1.1.5 {ECO:0000269|PubMed:8052601};
DE   AltName: Full=Isoleucyl-tRNA synthetase;
DE            Short=IRS;
DE            Short=IleRS;
GN   Name=IARS1 {ECO:0000312|HGNC:HGNC:5330}; Synonyms=IARS;
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], FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=8052601; DOI=10.1073/pnas.91.16.7435;
RA   Shiba K., Suzuki N., Shigesada K., Schimmel P., Noda T.;
RT   "Human cytoplasmic isoleucyl-tRNA synthetase: selective divergence of the
RT   anticodon-binding domain and acquisition of a new structural unit.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:7435-7439(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION,
RP   AND VARIANT ILE-769.
RC   TISSUE=Liver;
RX   PubMed=7721108; DOI=10.1016/0378-1119(94)00634-5;
RA   Nichols R.C., Raben N., Boerkoel C.F., Plotz P.H.;
RT   "Human isoleucyl-tRNA synthetase: sequence of the cDNA, alternative mRNA
RT   splicing, and the characteristics of an unusually long C-terminal
RT   extension.";
RL   Gene 155:299-304(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Trachea;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-1182.
RC   TISSUE=Colon endothelium;
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [6]
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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1047, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE 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   [8]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP   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   [9]
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   [10]
RP   SUBCELLULAR LOCATION, AND SUBUNIT.
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   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1047 AND SER-1049, AND
RP   IDENTIFICATION BY 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   [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   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1047, 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   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1047 AND THR-1058, AND
RP   IDENTIFICATION BY MASS 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   [15]
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   [16]
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   [17]
RP   VARIANTS TYR-302 AND THR-1188.
RX   PubMed=24706940; DOI=10.1136/jmedgenet-2013-102218;
RG   FORGE Canada Consortium;
RA   Smith A.C., Mears A.J., Bunker R., Ahmed A., MacKenzie M.,
RA   Schwartzentruber J.A., Beaulieu C.L., Ferretti E., Majewski J.,
RA   Bulman D.E., Celik F.C., Boycott K.M., Graham G.E.;
RT   "Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type
RT   spondylometaphyseal dysplasia.";
RL   J. Med. Genet. 51:470-474(2014).
RN   [18]
RP   INVOLVEMENT IN GRIDHH, VARIANTS GRIDHH GLY-370; LEU-437; ASP-992 AND
RP   ASN-1174, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=27426735; DOI=10.1016/j.ajhg.2016.05.027;
RA   Kopajtich R., Murayama K., Janecke A.R., Haack T.B., Breuer M.,
RA   Knisely A.S., Harting I., Ohashi T., Okazaki Y., Watanabe D., Tokuzawa Y.,
RA   Kotzaeridou U., Koelker S., Sauer S., Carl M., Straub S., Entenmann A.,
RA   Gizewski E., Feichtinger R.G., Mayr J.A., Lackner K., Strom T.M.,
RA   Meitinger T., Mueller T., Ohtake A., Hoffmann G.F., Prokisch H.,
RA   Staufner C.;
RT   "Biallelic IARS mutations cause growth retardation with prenatal onset,
RT   intellectual disability, muscular hypotonia, and infantile hepatopathy.";
RL   Am. J. Hum. Genet. 99:414-422(2016).
CC   -!- FUNCTION: Catalyzes the specific attachment of an amino acid to its
CC       cognate tRNA in a 2 step reaction: the amino acid (AA) is first
CC       activated by ATP to form AA-AMP and then transferred to the acceptor
CC       end of the tRNA. {ECO:0000269|PubMed:8052601}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-isoleucine + tRNA(Ile) = AMP + diphosphate + L-
CC         isoleucyl-tRNA(Ile); Xref=Rhea:RHEA:11060, Rhea:RHEA-COMP:9666,
CC         Rhea:RHEA-COMP:9695, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC         ChEBI:CHEBI:58045, ChEBI:CHEBI:78442, ChEBI:CHEBI:78528,
CC         ChEBI:CHEBI:456215; EC=6.1.1.5;
CC         Evidence={ECO:0000269|PubMed:8052601};
CC   -!- SUBUNIT: Part of a multisubunit complex that groups 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:19131329, PubMed:19289464). {ECO:0000269|PubMed:19131329,
CC       ECO:0000269|PubMed:19289464}.
CC   -!- INTERACTION:
CC       P41252; P07814: EPRS1; NbExp=7; IntAct=EBI-355303, EBI-355315;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27426735,
CC       ECO:0000269|PubMed:7721108}. Cytoplasm, cytosol
CC       {ECO:0000269|PubMed:19289464}.
CC   -!- TISSUE SPECIFICITY: Expressed in liver and muscle (at protein level).
CC       {ECO:0000269|PubMed:27426735}.
CC   -!- DISEASE: Growth retardation, impaired intellectual development,
CC       hypotonia, and hepatopathy (GRIDHH) [MIM:617093]: An autosomal
CC       recessive disorder characterized by severe growth retardation with
CC       prenatal onset, intellectual disability, muscular hypotonia, and
CC       hepatic dysfunction. {ECO:0000269|PubMed:27426735}. Note=The disease is
CC       caused 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=BAA05835.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; D28473; BAA05835.1; ALT_INIT; mRNA.
DR   EMBL; U04953; AAA80153.1; -; mRNA.
DR   EMBL; AK293014; BAF85703.1; -; mRNA.
DR   EMBL; BX537429; CAD97671.1; -; mRNA.
DR   EMBL; AL136097; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471089; EAW62813.1; -; Genomic_DNA.
DR   CCDS; CCDS6694.1; -.
DR   PIR; I59314; I59314.
DR   RefSeq; NP_002152.2; NM_002161.5.
DR   RefSeq; NP_038203.2; NM_013417.3.
DR   AlphaFoldDB; P41252; -.
DR   SMR; P41252; -.
DR   BioGRID; 109605; 375.
DR   ComplexPortal; CPX-2469; Multiaminoacyl-tRNA synthetase complex.
DR   CORUM; P41252; -.
DR   IntAct; P41252; 70.
DR   MINT; P41252; -.
DR   STRING; 9606.ENSP00000364794; -.
DR   BindingDB; P41252; -.
DR   ChEMBL; CHEMBL3235; -.
DR   DrugBank; DB00167; Isoleucine.
DR   DrugCentral; P41252; -.
DR   CarbonylDB; P41252; -.
DR   GlyGen; P41252; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P41252; -.
DR   MetOSite; P41252; -.
DR   PhosphoSitePlus; P41252; -.
DR   SwissPalm; P41252; -.
DR   BioMuta; IARS; -.
DR   DMDM; 239938717; -.
DR   EPD; P41252; -.
DR   jPOST; P41252; -.
DR   MassIVE; P41252; -.
DR   MaxQB; P41252; -.
DR   PaxDb; 9606-ENSP00000364794; -.
DR   PeptideAtlas; P41252; -.
DR   ProteomicsDB; 55454; -.
DR   Pumba; P41252; -.
DR   Antibodypedia; 28131; 150 antibodies from 21 providers.
DR   DNASU; 3376; -.
DR   Ensembl; ENST00000375643.7; ENSP00000364794.3; ENSG00000196305.19.
DR   Ensembl; ENST00000443024.7; ENSP00000406448.4; ENSG00000196305.19.
DR   Ensembl; ENST00000683565.1; ENSP00000507144.1; ENSG00000196305.19.
DR   Ensembl; ENST00000707248.1; ENSP00000516807.1; ENSG00000291356.1.
DR   Ensembl; ENST00000707249.1; ENSP00000516808.1; ENSG00000291356.1.
DR   Ensembl; ENST00000707251.1; ENSP00000516810.1; ENSG00000291356.1.
DR   GeneID; 3376; -.
DR   KEGG; hsa:3376; -.
DR   MANE-Select; ENST00000443024.7; ENSP00000406448.4; NM_002161.6; NP_002152.2.
DR   UCSC; uc004art.4; human.
DR   AGR; HGNC:5330; -.
DR   CTD; 3376; -.
DR   DisGeNET; 3376; -.
DR   GeneCards; IARS1; -.
DR   HGNC; HGNC:5330; IARS1.
DR   HPA; ENSG00000196305; Low tissue specificity.
DR   MalaCards; IARS1; -.
DR   MIM; 600709; gene.
DR   MIM; 617093; phenotype.
DR   neXtProt; NX_P41252; -.
DR   OpenTargets; ENSG00000196305; -.
DR   Orphanet; 541423; Growth delay-intellectual disability-hepatopathy syndrome.
DR   PharmGKB; PA29580; -.
DR   VEuPathDB; HostDB:ENSG00000196305; -.
DR   eggNOG; KOG0434; Eukaryota.
DR   GeneTree; ENSGT00550000074921; -.
DR   InParanoid; P41252; -.
DR   OMA; EIIVIHK; -.
DR   OrthoDB; 656at2759; -.
DR   PhylomeDB; P41252; -.
DR   PathwayCommons; P41252; -.
DR   Reactome; R-HSA-2408522; Selenoamino acid metabolism.
DR   Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation.
DR   SignaLink; P41252; -.
DR   SIGNOR; P41252; -.
DR   BioGRID-ORCS; 3376; 800 hits in 1127 CRISPR screens.
DR   ChiTaRS; IARS; human.
DR   GeneWiki; IARS; -.
DR   GenomeRNAi; 3376; -.
DR   Pharos; P41252; Tchem.
DR   PRO; PR:P41252; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; P41252; Protein.
DR   Bgee; ENSG00000196305; Expressed in cartilage tissue and 211 other cell types or tissues.
DR   ExpressionAtlas; P41252; baseline and differential.
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:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; 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:0051020; F:GTPase binding; IPI:UniProtKB.
DR   GO; GO:0004822; F:isoleucine-tRNA ligase activity; IDA:UniProtKB.
DR   GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR   GO; GO:0006428; P:isoleucyl-tRNA aminoacylation; IDA:UniProtKB.
DR   GO; GO:0001649; P:osteoblast differentiation; HDA:UniProtKB.
DR   GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome.
DR   CDD; cd07961; Anticodon_Ia_Ile_ABEc; 1.
DR   CDD; cd00818; IleRS_core; 1.
DR   Gene3D; 3.40.50.620; HUPs; 2.
DR   HAMAP; MF_02003; Ile_tRNA_synth_type2; 1.
DR   InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR   InterPro; IPR002300; aa-tRNA-synth_Ia.
DR   InterPro; IPR033709; Anticodon_Ile_ABEc.
DR   InterPro; IPR002301; Ile-tRNA-ligase.
DR   InterPro; IPR023586; Ile-tRNA-ligase_type2.
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; IPR009008; Val/Leu/Ile-tRNA-synth_edit.
DR   NCBIfam; TIGR00392; ileS; 1.
DR   PANTHER; PTHR42780:SF1; ISOLEUCINE--TRNA LIGASE, CYTOPLASMIC; 1.
DR   PANTHER; PTHR42780; SOLEUCYL-TRNA SYNTHETASE; 1.
DR   Pfam; PF08264; Anticodon_1; 1.
DR   Pfam; PF19302; DUF5915; 1.
DR   Pfam; PF00133; tRNA-synt_1; 1.
DR   PRINTS; PR00984; TRNASYNTHILE.
DR   SUPFAM; SSF47323; Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases; 1.
DR   SUPFAM; SSF52374; Nucleotidylyl transferase; 1.
DR   SUPFAM; SSF50677; ValRS/IleRS/LeuRS editing domain; 1.
DR   PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
DR   Genevisible; P41252; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm;
KW   Direct protein sequencing; Disease variant; Intellectual disability;
KW   Ligase; Nucleotide-binding; Phosphoprotein; Protein biosynthesis;
KW   Reference proteome.
FT   CHAIN           1..1262
FT                   /note="Isoleucine--tRNA ligase, cytoplasmic"
FT                   /id="PRO_0000098597"
FT   MOTIF           48..58
FT                   /note="'HIGH' region"
FT   MOTIF           600..604
FT                   /note="'KMSKS' region"
FT   BINDING         603
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0007744|PubMed:19413330"
FT   MOD_RES         1047
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18669648,
FT                   ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT                   ECO:0007744|PubMed:23186163"
FT   MOD_RES         1049
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:20068231"
FT   MOD_RES         1058
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VARIANT         302
FT                   /note="N -> Y (in dbSNP:rs140666586)"
FT                   /evidence="ECO:0000269|PubMed:24706940"
FT                   /id="VAR_071387"
FT   VARIANT         370
FT                   /note="V -> G (in GRIDHH; dbSNP:rs886037876)"
FT                   /evidence="ECO:0000269|PubMed:27426735"
FT                   /id="VAR_077055"
FT   VARIANT         437
FT                   /note="P -> L (in GRIDHH; dbSNP:rs886037874)"
FT                   /evidence="ECO:0000269|PubMed:27426735"
FT                   /id="VAR_077056"
FT   VARIANT         684
FT                   /note="T -> M (in dbSNP:rs2070053)"
FT                   /id="VAR_058300"
FT   VARIANT         769
FT                   /note="M -> I"
FT                   /evidence="ECO:0000269|PubMed:7721108"
FT                   /id="VAR_057951"
FT   VARIANT         992
FT                   /note="N -> D (in GRIDHH; dbSNP:rs886037877)"
FT                   /evidence="ECO:0000269|PubMed:27426735"
FT                   /id="VAR_077057"
FT   VARIANT         1174
FT                   /note="I -> N (in GRIDHH; dbSNP:rs886037873)"
FT                   /evidence="ECO:0000269|PubMed:27426735"
FT                   /id="VAR_077058"
FT   VARIANT         1182
FT                   /note="K -> E (in dbSNP:rs556155)"
FT                   /evidence="ECO:0000269|PubMed:17974005"
FT                   /id="VAR_057952"
FT   VARIANT         1188
FT                   /note="M -> T (in dbSNP:rs201071417)"
FT                   /evidence="ECO:0000269|PubMed:24706940"
FT                   /id="VAR_071388"
FT   CONFLICT        658
FT                   /note="N -> S (in Ref. 4; CAD97671)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1262 AA;  144498 MW;  73CB3967A6868005 CRC64;
     MLQQVPENIN FPAEEEKILE FWTEFNCFQE CLKQSKHKPK FTFYDGPPFA TGLPHYGHIL
     AGTIKDIVTR YAHQSGFHVD RRFGWDCHGL PVEYEIDKTL GIRGPEDVAK MGITEYNNQC
     RAIVMRYSAE WKSTVSRLGR WIDFDNDYKT LYPQFMESVW WVFKQLYDKG LVYRGVKVMP
     FSTACNTPLS NFESHQNYKD VQDPSVFVTF PLEEDETVSL VAWTTTPWTL PSNLAVCVNP
     EMQYVKIKDV ARGRLLILME ARLSALYKLE SDYEILERFP GAYLKGKKYR PLFDYFLKCK
     ENGAFTVLVD NYVKEEEGTG VVHQAPYFGA EDYRVCMDFN IIRKDSLPVC PVDASGCFTT
     EVTDFAGQYV KDADKSIIRT LKEQGRLLVA TTFTHSYPFC WRSDTPLIYK AVPSWFVRVE
     NMVDQLLRNN DLCYWVPELV REKRFGNWLK DARDWTISRN RYWGTPIPLW VSDDFEEVVC
     IGSVAELEEL SGAKISDLHR ESVDHLTIPS RCGKGSLHRI SEVFDCWFES GSMPYAQVHY
     PFENKREFED AFPADFIAEG IDQTRGWFYT LLVLATALFG QPPFKNVIVN GLVLASDGQK
     MSKRKKNYPD PVSIIQKYGA DALRLYLINS PVVRAENLRF KEEGVRDVLK DVLLPWYNAY
     RFLIQNVLRL QKEEEIEFLY NENTVRESPN ITDRWILSFM QSLIGFFETE MAAYRLYTVV
     PRLVKFVDIL TNWYVRMNRR RLKGENGMED CVMALETLFS VLLSLCRLMA PYTPFLTELM
     YQNLKVLIDP VSVQDKDTLS IHYLMLPRVR EELIDKKTES AVSQMQSVIE LGRVIRDRKT
     IPIKYPLKEI VVIHQDPEAL KDIKSLEKYI IEELNVRKVT LSTDKNKYGI RLRAEPDHMV
     LGKRLKGAFK AVMTSIKQLS SEELEQFQKT GTIVVEGHEL HDEDIRLMYT FDQATGGTAQ
     FEAHSDAQAL VLLDVTPDQS MVDEGMAREV INRIQKLRKK CNLVPTDEIT VYYKAKSEGT
     YLNSVIESHT EFIFTTIKAP LKPYPVSPSD KVLIQEKTQL KGSELEITLT RGSSLPGPAC
     AYVNLNICAN GSEQGGVLLL ENPKGDNRLD LLKLKSVVTS IFGVKNTELA VFHDETEIQN
     QTDLLSLSGK TLCVTAGSAP SLINSSSTLL CQYINLQLLN AKPQECLMGT VGTLLLENPL
     GQNGLTHQGL LYEAAKVFGL RSRKLKLFLN ETQTQEITED IPVKTLNMKT VYVSVLPTTA
     DF
//