ID   SYI_PYRFU               Reviewed;        1066 AA.
AC   P46214;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   26-SEP-2001, sequence version 2.
DT   27-MAR-2024, entry version 142.
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=PF1096;
OS   Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1).
OC   Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC   Pyrococcus.
OX   NCBI_TaxID=186497;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX   PubMed=10430560; DOI=10.1093/genetics/152.4.1299;
RA   Maeder D.L., Weiss R.B., Dunn D.M., Cherry J.L., Gonzalez J.M.,
RA   DiRuggiero J., Robb F.T.;
RT   "Divergence of the hyperthermophilic archaea Pyrococcus furiosus and P.
RT   horikoshii inferred from complete genomic sequences.";
RL   Genetics 152:1299-1305(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 87-632.
RX   PubMed=7708661; DOI=10.1073/pnas.92.7.2441;
RA   Brown J.R., Doolittle W.F.;
RT   "Root of the universal tree of life based on ancient aminoacyl-tRNA
RT   synthetase gene duplications.";
RL   Proc. Natl. Acad. Sci. U.S.A. 92:2441-2445(1995).
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; Evidence={ECO:0000255|HAMAP-
CC         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}.
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; AE009950; AAL81220.1; -; Genomic_DNA.
DR   EMBL; L37105; AAC41446.1; -; Genomic_DNA.
DR   RefSeq; WP_011012235.1; NZ_CP023154.1.
DR   AlphaFoldDB; P46214; -.
DR   SMR; P46214; -.
DR   STRING; 186497.PF1096; -.
DR   PaxDb; 186497-PF1096; -.
DR   GeneID; 41712904; -.
DR   KEGG; pfu:PF1096; -.
DR   PATRIC; fig|186497.12.peg.1156; -.
DR   eggNOG; arCOG00807; Archaea.
DR   HOGENOM; CLU_001493_1_1_2; -.
DR   OrthoDB; 30823at2157; -.
DR   PhylomeDB; P46214; -.
DR   Proteomes; UP000001013; 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   CDD; cd00818; IleRS_core; 1.
DR   Gene3D; 3.30.720.200; -; 1.
DR   Gene3D; 3.40.50.620; HUPs; 2.
DR   Gene3D; 3.90.740.10; Valyl/Leucyl/Isoleucyl-tRNA synthetase, editing domain; 1.
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; 2.
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; Metal-binding;
KW   Nucleotide-binding; Protein biosynthesis; Reference proteome; Zinc.
FT   CHAIN           1..1066
FT                   /note="Isoleucine--tRNA ligase"
FT                   /id="PRO_0000098589"
FT   MOTIF           49..59
FT                   /note="'HIGH' region"
FT   MOTIF           625..629
FT                   /note="'KMSKS' region"
FT   BINDING         628
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_02003"
FT   CONFLICT        88
FT                   /note="M -> T (in Ref. 2; AAC41446)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        119
FT                   /note="I -> V (in Ref. 2; AAC41446)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        167
FT                   /note="R -> W (in Ref. 2; AAC41446)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        241
FT                   /note="H -> L (in Ref. 2; AAC41446)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        250
FT                   /note="R -> G (in Ref. 2; AAC41446)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        494
FT                   /note="A -> T (in Ref. 2; AAC41446)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        501
FT                   /note="G -> S (in Ref. 2; AAC41446)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1066 AA;  125752 MW;  4704936EBC5D2272 CRC64;
     MIKEPEFRDY TPGKLEEKIE QFWKESNIYQ KVKELRKNGP KYYFLDGPPY VSGAIHLGTA
     WNKIIKDMII RFRTMQGYNV WRQPGYDMHG LPIEVKVEQA LGLKTKKEIE EKIGVENFIQ
     KCKEFALNNL RIMTEQFKML GVWMDWDNPY MTIKNEYIES AWFTLKRAWE KGLLEKDKRV
     LHWCPRCETA LAEHEVRGEY KLRKDPSIYV KFPVEGKENE YLLIWTTTPW TLPANLAVSA
     HPDYDYVKVR VDLNGREEYW ILAKALVEKV LGDIGVKGEV VEEFKGKELE GLRYVHILMD
     EYPRQKEFRE KYEWVHRVIL ADFVTLEEGT GLVHTAPGHG EEDFEVGQKY GLPVYSPVDD
     QGKYVEGKWK GVYVKEADPQ IIEHLKEKGY LVKAGEIEHK YPHCWRCKTP LIFRATDQWF
     LKVSKVKEKI IKENDEKVTW YPEWVKIRFD NGVRDSGDWV ISRQRYWGIP LPIWQSEDGE
     IYVVGSWKEL VELAVAIEVN GERIDLPESY EEKLKVIEEK LGPEDLHRPY VDAFIIKVNG
     KEMRRVKDVV DVWFDSGIAS WASLGYPRNK ELFEKLWPAD FIVEGEDQVT KWFYSQQAAS
     VIAFDTVPYR AVAMHGYVLD EKGDKMSKSL GNIIRPEEVV EKAGRDTFRF YMLWATNPWE
     NLKFSWKGVE QVRRMLNILW NVYVLSATYM SLDNFDPRNV KVEELEFREE DKWILSRVNN
     LIKEVENGIE TFYLTKATRA LYNFVVEDLS RWYVRLIRKR LWVEGDDPDK LAAYYTLWKV
     FDVLLRLMAP FTPYITEEIY QNIMRPFTGI ESVHMLDWPK PDESAVDEEL EREMEFIRRI
     VEAGSAARQK AKIKLRYPVR KIIIETQDDT VKKAVERLNY ILRDQLNAKE VVVGNVEREI
     TVKPNFAKVG PEFKGDARLV AKWISEHGLE LYEKGEVDVE IEGKKFHLTR EHIIVEENIP
     DFLVAEDFEG GRVYVDKTLT RELLAEGLAR EFVRRIQEMR KRLDLDVNDR IVVTIETTEE
     NRELLQENLE YIMRETRAIE VRFEEAKGYV VEWPEVQAKI GIEKIE
//