ID   SYI_STRPM               Reviewed;         933 AA.
AC   Q48SL8;
DT   20-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT   13-SEP-2005, sequence version 1.
DT   04-NOV-2026, entry version 118.
DE   RecName: Full=Isoleucine--tRNA ligase {ECO:0000255|HAMAP-Rule:MF_02002};
DE            EC=6.1.1.5 {ECO:0000255|HAMAP-Rule:MF_02002};
DE   AltName: Full=Isoleucyl-tRNA synthetase {ECO:0000255|HAMAP-Rule:MF_02002};
DE            Short=IleRS {ECO:0000255|HAMAP-Rule:MF_02002};
GN   Name=ileS {ECO:0000255|HAMAP-Rule:MF_02002};
GN   OrderedLocusNames=M28_Spy1182;
OS   Streptococcus pyogenes serotype M28 (strain MGAS6180).
OC   Bacteria; Bacillati; Bacillota; Bacilli; Lactobacillales; Streptococcaceae;
OC   Streptococcus.
OX   NCBI_TaxID=319701;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MGAS6180;
RX   PubMed=16088825; DOI=10.1086/430618;
RA   Green N.M., Zhang S., Porcella S.F., Nagiec M.J., Barbian K.D., Beres S.B.,
RA   Lefebvre R.B., Musser J.M.;
RT   "Genome sequence of a serotype M28 strain of group A Streptococcus:
RT   potential new insights into puerperal sepsis and bacterial disease
RT   specificity.";
RL   J. Infect. Dis. 192:760-770(2005).
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_02002}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=tRNA(Ile) + L-isoleucine + ATP = L-isoleucyl-tRNA(Ile) + AMP +
CC         diphosphate; Xref=Rhea:RHEA:11060, Rhea:RHEA-COMP:9666, Rhea:RHEA-
CC         COMP:9695, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58045,
CC         ChEBI:CHEBI:78442, ChEBI:CHEBI:78528, ChEBI:CHEBI:456215; EC=6.1.1.5;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_02002};
CC   -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_02002}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_02002}.
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_02002}.
CC   -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC       IleS type 1 subfamily. {ECO:0000255|HAMAP-Rule:MF_02002}.
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DR   EMBL; CP000056; AAX72292.1; -; Genomic_DNA.
DR   RefSeq; WP_011284956.1; NC_007296.2.
DR   AlphaFoldDB; Q48SL8; -.
DR   SMR; Q48SL8; -.
DR   KEGG; spb:M28_Spy1182; -.
DR   HOGENOM; CLU_001493_7_1_9; -.
DR   OMA; AACGHYL; -.
DR   GO; GO:0005829; C:cytosol; IEA:TreeGrafter.
DR   GO; GO:0002161; F:aminoacyl-tRNA deacylase 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:0006428; P:isoleucyl-tRNA aminoacylation; IEA:UniProtKB-UniRule.
DR   CDD; cd07960; Anticodon_Ia_Ile_BEm; 1.
DR   CDD; cd00818; IleRS_core; 1.
DR   FunFam; 1.10.10.830:FF:000001; Isoleucine--tRNA ligase; 1.
DR   FunFam; 1.10.730.20:FF:000001; Isoleucine--tRNA ligase; 1.
DR   FunFam; 3.40.50.620:FF:000092; Isoleucine--tRNA ligase; 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   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; IPR050081; Ile-tRNA_ligase.
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; 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   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.
PE   3: Inferred from homology;
KW   Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; Ligase;
KW   Nucleotide-binding; Protein biosynthesis.
FT   CHAIN           1..933
FT                   /note="Isoleucine--tRNA ligase"
FT                   /id="PRO_0000098483"
FT   MOTIF           57..67
FT                   /note="'HIGH' region"
FT   MOTIF           595..599
FT                   /note="'KMSKS' region"
FT   BINDING         554
FT                   /ligand="L-isoleucyl-5'-AMP"
FT                   /ligand_id="ChEBI:CHEBI:178002"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02002"
FT   BINDING         598
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02002"
SQ   SEQUENCE   933 AA;  105069 MW;  88EB823B25979B02 CRC64;
     MKLKETLNLG KTAFPMRAGL PNKEPQWQAA WEQAELYKKR QELNAGKPAF HLHDGPPYAN
     GNIHVGHALN KISKDIIVRS KSMSGFQAPY VPGWDTHGLP IEQVLAKQGI KRKEMDLAEY
     LEMCRQYALS QVDKQRDDFK RLGVSADWEN PYVTLDPQFE ADQIRVFGAM AEKGYIYRGA
     KPVYWSWSSE SALAEAEIEY HDIDSTSLYY ANKVKDGKGI LDTNTYIVVW TTTPFTVTAS
     RGLTVGPDMD YLVVKPAGSD RQYVVAEGLL DSLAGKFGWE SFETLASHKG ADLEYIVTEH
     PWDTDVEELV ILGDHVTLES GTGIVHTAPG FGEDDYNVGT KYKLEVAVTV DERGLMTENA
     GPDFHGQFYN KVTPIVIDKL GDLLLAQEVI NHSYPFDWRT KKPIIWRAVP QWFASVSDFR
     QDILDEIEKT TFHPSWGETR LYNMIRDRGD WVISRQRAWG VPLPIFYAED GTAIMTKEVT
     DHVADLFQEN GSIIWWQKEA KDLLPEGFTH PGSPNGEFTK ETDIMDVWFD SGSSWNGVMN
     TKENLSYPAD LYLEGSDQYR GWFNSSLITS VAVNGHAPYK AILSQGFVLD GKGEKMSKSK
     GNIISPNDVA KQYGADILRL WVASVDTDND VRVSMEILGQ VSETYRKIRN TLRFLIANTS
     DFNPATDTVA YADLGAVDKY MTIVFNQLVA TITDAYERYD FMAIYKAVVN FVTVDLSAFY
     LDFAKDVVYI EAANSLERRR MQTVFYDILV KITKLLTPIL PHTTEEIWSY LEHESEAFVQ
     LAEMPVAETF SAQEDILEAW SAFMTLRTQA QKALEEARNA KIIGKSLEAH LTIYASEEVK
     TLLTALDSDI ALLLIVSQLT IADLADAPAD AVAFEGIAFM VEHAIGEVCE RSRRIDPTTR
     MRSYNAFVCD HSAKIIEENF PEAVAEGFEE SDK
//