ID   SYI_METTH               Reviewed;        1044 AA.
AC   O27428;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   03-AUG-2022, entry version 137.
DE   RecName: Full=Isoleucine--tRNA ligase {ECO:0000255|HAMAP-Rule:MF_02003};
DE            EC=6.1.1.5 {ECO:0000255|HAMAP-Rule:MF_02003};
DE   AltName: Full=Isoleucyl-tRNA synthetase {ECO:0000255|HAMAP-Rule:MF_02003};
DE            Short=IleRS {ECO:0000255|HAMAP-Rule:MF_02003};
GN   Name=ileS {ECO:0000255|HAMAP-Rule:MF_02003}; OrderedLocusNames=MTH_1375;
OS   Methanothermobacter thermautotrophicus (strain ATCC 29096 / DSM 1053 / JCM
OS   10044 / NBRC 100330 / Delta H) (Methanobacterium thermoautotrophicum).
OC   Archaea; Euryarchaeota; Methanomada group; Methanobacteria;
OC   Methanobacteriales; Methanobacteriaceae; Methanothermobacter.
OX   NCBI_TaxID=187420;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 29096 / DSM 1053 / JCM 10044 / NBRC 100330 / Delta H;
RX   PubMed=9371463; DOI=10.1128/jb.179.22.7135-7155.1997;
RA   Smith D.R., Doucette-Stamm L.A., Deloughery C., Lee H.-M., Dubois J.,
RA   Aldredge T., Bashirzadeh R., Blakely D., Cook R., Gilbert K., Harrison D.,
RA   Hoang L., Keagle P., Lumm W., Pothier B., Qiu D., Spadafora R., Vicare R.,
RA   Wang Y., Wierzbowski J., Gibson R., Jiwani N., Caruso A., Bush D.,
RA   Safer H., Patwell D., Prabhakar S., McDougall S., Shimer G., Goyal A.,
RA   Pietrovski S., Church G.M., Daniels C.J., Mao J.-I., Rice P., Noelling J.,
RA   Reeve J.N.;
RT   "Complete genome sequence of Methanobacterium thermoautotrophicum deltaH:
RT   functional analysis and comparative genomics.";
RL   J. Bacteriol. 179:7135-7155(1997).
CC   -!- FUNCTION: Catalyzes the attachment of isoleucine to tRNA(Ile). As IleRS
CC       can inadvertently accommodate and process structurally similar amino
CC       acids such as valine, to avoid such errors it has two additional
CC       distinct tRNA(Ile)-dependent editing activities. One activity is
CC       designated as 'pretransfer' editing and involves the hydrolysis of
CC       activated Val-AMP. The other activity is designated 'posttransfer'
CC       editing and involves deacylation of mischarged Val-tRNA(Ile).
CC       {ECO:0000255|HAMAP-Rule:MF_02003}.
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; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_02003};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_02003};
CC   -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_02003}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_02003}.
CC   -!- DOMAIN: IleRS has two distinct active sites: one for aminoacylation and
CC       one for editing. The misactivated valine is translocated from the
CC       active site to the editing site, which sterically excludes the
CC       correctly activated isoleucine. The single editing site contains two
CC       valyl binding pockets, one specific for each substrate (Val-AMP or Val-
CC       tRNA(Ile)). {ECO:0000255|HAMAP-Rule:MF_02003}.
CC   -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC       IleS type 2 subfamily. {ECO:0000255|HAMAP-Rule:MF_02003}.
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DR   EMBL; AE000666; AAB85852.1; -; Genomic_DNA.
DR   PIR; H69049; H69049.
DR   RefSeq; WP_010876987.1; NC_000916.1.
DR   AlphaFoldDB; O27428; -.
DR   SMR; O27428; -.
DR   STRING; 187420.MTH_1375; -.
DR   EnsemblBacteria; AAB85852; AAB85852; MTH_1375.
DR   GeneID; 1471092; -.
DR   KEGG; mth:MTH_1375; -.
DR   PATRIC; fig|187420.15.peg.1340; -.
DR   HOGENOM; CLU_001493_1_1_2; -.
DR   OMA; HLGTAWN; -.
DR   Proteomes; UP000005223; Chromosome.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0002161; F:aminoacyl-tRNA editing activity; IEA:InterPro.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0004822; F:isoleucine-tRNA ligase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0006428; P:isoleucyl-tRNA aminoacylation; IEA:UniProtKB-UniRule.
DR   CDD; cd07961; Anticodon_Ia_Ile_ABEc; 1.
DR   Gene3D; 3.40.50.620; -; 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   PANTHER; PTHR42780; PTHR42780; 1.
DR   Pfam; PF08264; Anticodon_1; 1.
DR   Pfam; PF00133; tRNA-synt_1; 1.
DR   PRINTS; PR00984; TRNASYNTHILE.
DR   SUPFAM; SSF47323; SSF47323; 1.
DR   SUPFAM; SSF50677; SSF50677; 1.
DR   TIGRFAMs; TIGR00392; ileS; 1.
DR   PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
PE   3: Inferred from homology;
KW   Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Ligase; Metal-binding;
KW   Nucleotide-binding; Protein biosynthesis; Reference proteome; Zinc.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250"
FT   CHAIN           2..1044
FT                   /note="Isoleucine--tRNA ligase"
FT                   /id="PRO_0000098578"
FT   MOTIF           49..59
FT                   /note="'HIGH' region"
FT   MOTIF           591..595
FT                   /note="'KMSKS' region"
FT   BINDING         594
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02003"
SQ   SEQUENCE   1044 AA;  120980 MW;  BDE882817791051B CRC64;
     MPIQEAEKSY RPHRIEEKVQ SFWEERDIYE RVKELREDRP RYSFLDGPPY CSGRIHLGTA
     WNKIMKDTYL RFKSMKGFNV RRQPGWDTHG LPIEHKVEGL LGVRSKKDIE DKIGIEEFVN
     KCREFAVENK AVMTGQFQRL GVWMDWDDPY VTFDPAYMES CWWTLKRAHE KDLLVRDLRV
     ITWCPRCETA LALAEIDYHD KEDPSIYVKF PVSGDTHILV WTTTPWTLPA NMAVAVHPDF
     EYAYARLDGE TYIMAEALVE KVLGEEAEIL KRVKGTELEG LTYRHPLDDE VPLHREIEHR
     VILGDHVTLT EGTGCVHTAP GHGPEDFEIG KKYGLEVICP VDEAGIFTEE AGKYSGRFVK
     DADEDIIADL RSKGLLLKAG TISHRYGFCW RCKTPIIYLA TEQWFLKITE IKDKMLRELD
     RVQWVPSWAG ESRFRNWIEN ARDWTISRQR YWGIPIPIWI CEECDSIHVV GSIDELRELA
     VEGELEGDFI HRPHVDRIVL ECGECGGRMK RTPDVLDVWI DSGVAGWAAL HYPSETELFR
     EWFPYDFITE GHDQTRGWFY SQLGCGVIAL DEVPYRRVLM HGFTLDEEGR KMSKSLGNVV
     EPEDVIEKYG ADVLRFYLLW ENKPWEDLKF VWDELRNVNK MFNILWNVYV FATTYMSLDR
     FQPGDHSAED LSFRDEDRWI LSRINSVALK VTEAIENLHF HRATREIHDF IVEDLSRWYI
     RLIRSRTWIE RDDPDKLAAY HTLYTVLKTL IVTLSPMAPH VCEDIYQNLV RGAEPDSPES
     IHMLDWILDE GAVDSQLEAD MDIVREIIEA CARARDTARY KLRWPVREMV VVSEDEGVLK
     AAESLKNVIA EQANAKSIKT STEFPDMKII ARPNPATLGP RLRQDIPLVM RELEGADGSA
     VKAALDSDGE FTVETDGKKF KLTSEDIVFE TELPENIVSA QFDGGSVFID TELTPEIMSE
     AMARELVRRI QDMRKDLDLD VEASIEVSVK CSEEFRELTE PQREFIENEV RASTLSFDYS
     ELEYTKEWKI SDENLIISIK PAKV