ID   SYIM_MOUSE              Reviewed;        1012 AA.
AC   Q8BIJ6; Q3TKT8; Q8BIJ0; Q8BIP3;
DT   02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 153.
DE   RecName: Full=Isoleucine--tRNA ligase, mitochondrial {ECO:0000305};
DE            EC=6.1.1.5 {ECO:0000250|UniProtKB:P00956};
DE   AltName: Full=Isoleucyl-tRNA synthetase;
DE            Short=IleRS;
DE   Flags: Precursor;
GN   Name=Iars2 {ECO:0000312|MGI:MGI:1919586};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Cerebellum, Head, and Liver;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J;
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   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [4]
RP   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-56; LYS-74; LYS-194; LYS-241;
RP   LYS-479; LYS-500; LYS-775 AND LYS-781, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast, and Liver;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
RN   [5]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-74; LYS-725 AND LYS-775, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA   Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA   Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT   "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT   identifies substrates of SIRT3 in metabolic pathways.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC   -!- FUNCTION: Aminoacyl-tRNA synthetase that catalyzes the specific
CC       attachment of isoleucine to its cognate tRNA (tRNA(Ile)).
CC       {ECO:0000250|UniProtKB:P00956}.
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:0000250|UniProtKB:P00956};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11061;
CC         Evidence={ECO:0000305};
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC       {ECO:0000305}.
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DR   EMBL; AK166832; BAE39055.1; -; mRNA.
DR   EMBL; AK036182; BAC29337.1; -; mRNA.
DR   EMBL; AK048653; BAC33410.1; -; mRNA.
DR   EMBL; AK050358; BAC34208.1; -; mRNA.
DR   EMBL; BC052403; AAH52403.1; -; mRNA.
DR   CCDS; CCDS15596.1; -.
DR   RefSeq; NP_941055.1; NM_198653.2.
DR   AlphaFoldDB; Q8BIJ6; -.
DR   SMR; Q8BIJ6; -.
DR   BioGRID; 237874; 12.
DR   STRING; 10090.ENSMUSP00000027921; -.
DR   GlyGen; Q8BIJ6; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8BIJ6; -.
DR   PhosphoSitePlus; Q8BIJ6; -.
DR   SwissPalm; Q8BIJ6; -.
DR   EPD; Q8BIJ6; -.
DR   jPOST; Q8BIJ6; -.
DR   MaxQB; Q8BIJ6; -.
DR   PaxDb; 10090-ENSMUSP00000027921; -.
DR   PeptideAtlas; Q8BIJ6; -.
DR   ProteomicsDB; 253437; -.
DR   Pumba; Q8BIJ6; -.
DR   Antibodypedia; 20735; 184 antibodies from 29 providers.
DR   DNASU; 381314; -.
DR   Ensembl; ENSMUST00000027921.11; ENSMUSP00000027921.5; ENSMUSG00000026618.12.
DR   GeneID; 381314; -.
DR   KEGG; mmu:381314; -.
DR   UCSC; uc007dyz.1; mouse.
DR   AGR; MGI:1919586; -.
DR   CTD; 55699; -.
DR   MGI; MGI:1919586; Iars2.
DR   VEuPathDB; HostDB:ENSMUSG00000026618; -.
DR   eggNOG; KOG0433; Eukaryota.
DR   GeneTree; ENSGT00550000074910; -.
DR   HOGENOM; CLU_001493_7_2_1; -.
DR   InParanoid; Q8BIJ6; -.
DR   OMA; HCWRCKT; -.
DR   OrthoDB; 656at2759; -.
DR   PhylomeDB; Q8BIJ6; -.
DR   TreeFam; TF300518; -.
DR   BioGRID-ORCS; 381314; 31 hits in 80 CRISPR screens.
DR   ChiTaRS; Iars2; mouse.
DR   PRO; PR:Q8BIJ6; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; Q8BIJ6; Protein.
DR   Bgee; ENSMUSG00000026618; Expressed in migratory enteric neural crest cell and 271 other cell types or tissues.
DR   ExpressionAtlas; Q8BIJ6; baseline and differential.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0002161; F:aminoacyl-tRNA editing activity; IEA:InterPro.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004822; F:isoleucine-tRNA ligase activity; IBA:GO_Central.
DR   GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR   GO; GO:0006428; P:isoleucyl-tRNA aminoacylation; IBA:GO_Central.
DR   GO; GO:0032543; P:mitochondrial translation; IBA:GO_Central.
DR   CDD; cd07960; Anticodon_Ia_Ile_BEm; 1.
DR   Gene3D; 1.10.730.20; -; 1.
DR   Gene3D; 3.40.50.620; HUPs; 2.
DR   Gene3D; 1.10.10.830; Ile-tRNA synthetase CP2 domain-like; 1.
DR   Gene3D; 3.90.740.10; Valyl/Leucyl/Isoleucyl-tRNA synthetase, editing domain; 1.
DR   HAMAP; MF_02002; Ile_tRNA_synth_type1; 1.
DR   InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR   InterPro; IPR002300; aa-tRNA-synth_Ia.
DR   InterPro; IPR033708; Anticodon_Ile_BEm.
DR   InterPro; IPR002301; Ile-tRNA-ligase.
DR   InterPro; IPR023585; Ile-tRNA-ligase_type1.
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   InterPro; IPR010663; Znf_FPG/IleRS.
DR   NCBIfam; TIGR00392; ileS; 1.
DR   PANTHER; PTHR42765:SF1; ISOLEUCINE--TRNA LIGASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR42765; SOLEUCYL-TRNA SYNTHETASE; 1.
DR   Pfam; PF08264; Anticodon_1; 1.
DR   Pfam; PF00133; tRNA-synt_1; 1.
DR   Pfam; PF06827; zf-FPG_IleRS; 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; Q8BIJ6; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Ligase; Mitochondrion;
KW   Nucleotide-binding; Protein biosynthesis; Reference proteome;
KW   Transit peptide.
FT   TRANSIT         1..48
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           49..1012
FT                   /note="Isoleucine--tRNA ligase, mitochondrial"
FT                   /id="PRO_0000233337"
FT   MOTIF           116..126
FT                   /note="'HIGH' region"
FT                   /evidence="ECO:0000305"
FT   MOTIF           664..668
FT                   /note="'KMSKS' region"
FT                   /evidence="ECO:0000305"
FT   BINDING         664
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P00956"
FT   BINDING         667
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:P00956"
FT   MOD_RES         56
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         74
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         74
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         194
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         233
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NSE4"
FT   MOD_RES         241
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NSE4"
FT   MOD_RES         241
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         479
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         500
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         725
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         775
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         775
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         781
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NSE4"
FT   MOD_RES         781
FT                   /note="N6-succinyllysine; alternate"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   CONFLICT        68
FT                   /note="Q -> K (in Ref. 1; BAC29337)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        86
FT                   /note="E -> G (in Ref. 1; BAE39055)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        119
FT                   /note="N -> K (in Ref. 1; BAC29337)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        709
FT                   /note="V -> M (in Ref. 1; BAC34208)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        819
FT                   /note="C -> Y (in Ref. 1; BAE39055)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1012 AA;  112804 MW;  A4663D3A1BC3D678 CRC64;
     MHWGLCPRGP GAAAVAAAGS FWGPARLPSR LGCLGMTRRL VVRSVAGADS PQSSSKGGRY
     RDTVLLPQTS FPMKLLGRQQ SDMELEIQQK CGFSELYSWQ RERKVKTEFC LHDGPPYANG
     DPHVGHALNK ILKDIANRFH MMRGSKVHFV PGWDCHGLPI ETKVLSELGV DAQSLSAMEI
     REKARSFAQA AIEKQKSAFV RWGVMADWNN CYYTFDPKYE AKQLRVFYQM YEKGLVYRSY
     KPVYWSPSSR TALAEAELEY NPEHVSRSIY VRFPLLRPPP KLESLTDASS PVSVLVWTTQ
     PWTIPANQAI CYMPEAKYAV VKCSASGHLY ILAEDKIAPV ASALETTFDV VAAFSGVDLE
     GGTCSHPLTP DKVSPLLPAT HVTMAKGTGL VHTAPAHGME DYSVASQHSL PMDCLVDEGG
     MFTDAAGPEL QNKAVLKEGT DVVIKMLQAT KNVLKEENIV HSYPCDWRTK TPVLIRASKQ
     WFVNITDIKA AAKESLKTVK FIPGAALNSM TDMLDRRPYW CISRQRVWGV PIPVFHHKTK
     DEYLINSQTT EHIIKLVEQH GSDVWWTLPA EQLLPAEVLA QAGGPGALEY APGQDILDIW
     FDSGTSWSCV LQDTQQRADL YLEGKDQLGG WFQSSLLTSV ATRSKAPFRT VMVHGFTLGE
     KGEKMSKSLG NVINPDTIIS GGKDHSKEPP YGADILRWWI AESNVFTEVT IGPSVLSAAR
     DDISKLRNTL RFLLGNLTGF NPETDSVPVK NMYVIDQYML HLIQDFATKI TDSYKQYDFG
     KVVRLLKAFY TRELSSFYFS IVKDRLYCEN EKDPKRRSCQ TALAEILDVL VRAFAPILPH
     LAEEVFQHIP YVTEPKSVFR TGWINTSSIW KKPGLEEAVE SACAMRDSFL GSIPGKNAAE
     YEVIIVIEPG LLFEIMEMLQ AEETSSTSQL NELMMASQTT LLAQEPRERT AGDIELTGTF
     VINLEGGDIR EESSYKVIVV PTAREKCPRC WKHTSETADA LCPRCAEVIG AK
//