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Database: UniProt
Entry: HIS5_YEAST
LinkDB: HIS5_YEAST
Original site: HIS5_YEAST 
ID   HIS5_YEAST              Reviewed;         552 AA.
AC   P33734; D6VQP4;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1994, sequence version 2.
DT   08-NOV-2023, entry version 192.
DE   RecName: Full=Imidazole glycerol phosphate synthase hisHF;
DE            Short=IGP synthase;
DE            Short=IGPS;
DE            Short=ImGP synthase;
DE            EC=4.3.2.10;
DE   Includes:
DE     RecName: Full=Glutaminase;
DE              EC=3.5.1.2;
DE   Includes:
DE     RecName: Full=Cyclase;
GN   Name=HIS7; OrderedLocusNames=YBR248C; ORFNames=YBR1640;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8366040; DOI=10.1128/jb.175.17.5548-5558.1993;
RA   Kuenzler M., Balmelli T., Egli C.M., Paravicini G., Braus G.H.;
RT   "Cloning, primary structure, and regulation of the HIS7 gene encoding a
RT   bifunctional glutamine amidotransferase: cyclase from Saccharomyces
RT   cerevisiae.";
RL   J. Bacteriol. 175:5548-5558(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA   Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA   Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA   Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA   Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA   Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA   Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA   Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA   Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA   Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA   Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA   Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA   Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA   Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA   Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA   Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA   Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA   Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA   Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA   Mewes H.-W., Kleine K.;
RT   "Complete DNA sequence of yeast chromosome II.";
RL   EMBO J. 13:5795-5809(1994).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   MUTAGENESIS OF ARG-239; LYS-258 AND LYS-360, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=12795596; DOI=10.1021/bi034314l;
RA   Myers R.S., Jensen J.R., Deras I.L., Smith J.L., Davisson V.J.;
RT   "Substrate-induced changes in the ammonia channel for imidazole glycerol
RT   phosphate synthase.";
RL   Biochemistry 42:7013-7022(2003).
RN   [5]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG, AND
RP   SUBUNIT.
RX   PubMed=11591353; DOI=10.1016/s0969-2126(01)00661-x;
RA   Chaudhuri B.N., Lange S.C., Myers R.S., Chittur S.V., Davisson V.J.,
RA   Smith J.L.;
RT   "Crystal structure of imidazole glycerol phosphate synthase: a tunnel
RT   through a (beta/alpha)8 barrel joins two active sites.";
RL   Structure 9:987-997(2001).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF APOENZYME; IN COMPLEX WITH
RP   SUBSTRATE AND SUBSTRATE ANALOG AND IN COMPLEX WITH INHIBITOR.
RX   PubMed=12795595; DOI=10.1021/bi034320h;
RA   Chaudhuri B.N., Lange S.C., Myers R.S., Davisson V.J., Smith J.L.;
RT   "Toward understanding the mechanism of the complex cyclization reaction
RT   catalyzed by imidazole glycerolphosphate synthase: crystal structures of a
RT   ternary complex and the free enzyme.";
RL   Biochemistry 42:7003-7012(2003).
CC   -!- FUNCTION: IGPS catalyzes the conversion of PRFAR and glutamine to IGP,
CC       AICAR and glutamate. The glutaminase domain produces the ammonia
CC       necessary for the cyclase domain to produce IGP and AICAR from PRFAR.
CC       The ammonia is channeled to the active site of the cyclase domain.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=5-[(5-phospho-1-deoxy-D-ribulos-1-ylimino)methylamino]-1-(5-
CC         phospho-beta-D-ribosyl)imidazole-4-carboxamide + L-glutamine = 5-
CC         amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide + D-
CC         erythro-1-(imidazol-4-yl)glycerol 3-phosphate + H(+) + L-glutamate;
CC         Xref=Rhea:RHEA:24793, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985,
CC         ChEBI:CHEBI:58278, ChEBI:CHEBI:58359, ChEBI:CHEBI:58475,
CC         ChEBI:CHEBI:58525; EC=4.3.2.10;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + L-glutamine = L-glutamate + NH4(+);
CC         Xref=Rhea:RHEA:15889, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938,
CC         ChEBI:CHEBI:29985, ChEBI:CHEBI:58359; EC=3.5.1.2;
CC   -!- PATHWAY: Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine
CC       from 5-phospho-alpha-D-ribose 1-diphosphate: step 5/9.
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11591353,
CC       ECO:0000269|PubMed:12795595}.
CC   -!- INDUCTION: By amino acid starvation. It has a GCN4-dependent and a
CC       GCN4-independent (basal) expression.
CC   -!- MISCELLANEOUS: Present with 11800 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the HisA/HisF family.
CC       {ECO:0000305}.
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DR   EMBL; X69815; CAA49469.1; -; Genomic_DNA.
DR   EMBL; Z36117; CAA85211.1; -; Genomic_DNA.
DR   EMBL; BK006936; DAA07364.1; -; Genomic_DNA.
DR   PIR; S46125; S46125.
DR   RefSeq; NP_009807.3; NM_001178596.3.
DR   PDB; 1JVN; X-ray; 2.10 A; A/B=1-552.
DR   PDB; 1OX4; X-ray; 2.50 A; A/B=1-552.
DR   PDB; 1OX5; X-ray; 2.50 A; A/B=1-552.
DR   PDB; 1OX6; X-ray; 2.40 A; A/B=1-552.
DR   PDBsum; 1JVN; -.
DR   PDBsum; 1OX4; -.
DR   PDBsum; 1OX5; -.
DR   PDBsum; 1OX6; -.
DR   AlphaFoldDB; P33734; -.
DR   SMR; P33734; -.
DR   BioGRID; 32943; 16.
DR   DIP; DIP-4222N; -.
DR   MINT; P33734; -.
DR   STRING; 4932.YBR248C; -.
DR   iPTMnet; P33734; -.
DR   MaxQB; P33734; -.
DR   PaxDb; 4932-YBR248C; -.
DR   PeptideAtlas; P33734; -.
DR   EnsemblFungi; YBR248C_mRNA; YBR248C; YBR248C.
DR   GeneID; 852550; -.
DR   KEGG; sce:YBR248C; -.
DR   AGR; SGD:S000000452; -.
DR   SGD; S000000452; HIS7.
DR   VEuPathDB; FungiDB:YBR248C; -.
DR   eggNOG; KOG0623; Eukaryota.
DR   HOGENOM; CLU_037550_0_0_1; -.
DR   InParanoid; P33734; -.
DR   OMA; EAMGTGE; -.
DR   OrthoDB; 2782495at2759; -.
DR   BioCyc; YEAST:YBR248C-MONOMER; -.
DR   BRENDA; 4.3.1.B2; 984.
DR   BRENDA; 4.3.2.10; 984.
DR   SABIO-RK; P33734; -.
DR   UniPathway; UPA00031; UER00010.
DR   BioGRID-ORCS; 852550; 2 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P33734; -.
DR   PRO; PR:P33734; -.
DR   Proteomes; UP000002311; Chromosome II.
DR   RNAct; P33734; Protein.
DR   GO; GO:0005737; C:cytoplasm; IC:SGD.
DR   GO; GO:0004359; F:glutaminase activity; IDA:SGD.
DR   GO; GO:0000107; F:imidazoleglycerol-phosphate synthase activity; IDA:SGD.
DR   GO; GO:0016833; F:oxo-acid-lyase activity; IEA:InterPro.
DR   GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0000105; P:histidine biosynthetic process; IMP:SGD.
DR   CDD; cd01748; GATase1_IGP_Synthase; 1.
DR   CDD; cd04731; HisF; 1.
DR   Gene3D; 3.40.50.880; -; 1.
DR   Gene3D; 3.20.20.70; Aldolase class I; 1.
DR   HAMAP; MF_00278; HisH; 1.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR029062; Class_I_gatase-like.
DR   InterPro; IPR017926; GATASE.
DR   InterPro; IPR006062; His_biosynth.
DR   InterPro; IPR004651; HisF.
DR   InterPro; IPR014640; IGPS_HisHF.
DR   InterPro; IPR010139; Imidazole-glycPsynth_HisH.
DR   InterPro; IPR011060; RibuloseP-bd_barrel.
DR   NCBIfam; TIGR00735; hisF; 1.
DR   NCBIfam; TIGR01855; IMP_synth_hisH; 1.
DR   PANTHER; PTHR21235:SF2; IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE HISHF; 1.
DR   PANTHER; PTHR21235; IMIDAZOLE GLYCEROL PHOSPHATE SYNTHASE SUBUNIT HISF/H IGP SYNTHASE SUBUNIT HISF/H; 1.
DR   Pfam; PF00117; GATase; 1.
DR   Pfam; PF00977; His_biosynth; 1.
DR   PIRSF; PIRSF036936; IGPS_HisHF; 1.
DR   SUPFAM; SSF52317; Class I glutamine amidotransferase-like; 1.
DR   SUPFAM; SSF51366; Ribulose-phoshate binding barrel; 1.
DR   PROSITE; PS51273; GATASE_TYPE_1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Amino-acid biosynthesis; Glutamine amidotransferase;
KW   Histidine biosynthesis; Hydrolase; Lyase; Multifunctional enzyme;
KW   Reference proteome; Stress response.
FT   CHAIN           1..552
FT                   /note="Imidazole glycerol phosphate synthase hisHF"
FT                   /id="PRO_0000152476"
FT   DOMAIN          3..218
FT                   /note="Glutamine amidotransferase type-1"
FT   REGION          236..552
FT                   /note="Cyclase"
FT   REGION          364..365
FT                   /note="PRFAR binding"
FT   REGION          402..404
FT                   /note="PRFAR binding"
FT   REGION          474..475
FT                   /note="PRFAR binding"
FT   REGION          500..501
FT                   /note="PRFAR binding"
FT   REGION          523..524
FT                   /note="PRFAR binding"
FT   ACT_SITE        83
FT                   /note="For GATase activity"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        193
FT                   /note="For GATase activity"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        195
FT                   /note="For GATase activity"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        245
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        404
FT                   /evidence="ECO:0000255"
FT   BINDING         83
FT                   /ligand="L-glutamine"
FT                   /ligand_id="ChEBI:CHEBI:58359"
FT                   /note="covalent"
FT   BINDING         332
FT                   /ligand="substrate"
FT   BINDING         469
FT                   /ligand="substrate"
FT   MUTAGEN         239
FT                   /note="R->A,H,K: 1000-fold decrease in catalytic
FT                   efficiency. Uncoupling of glutaminase activity from the
FT                   cyclase activity."
FT                   /evidence="ECO:0000269|PubMed:12795596"
FT   MUTAGEN         258
FT                   /note="K->A: No activity. Uncoupling of glutaminase
FT                   activity from the cyclase activity."
FT                   /evidence="ECO:0000269|PubMed:12795596"
FT   MUTAGEN         258
FT                   /note="K->R: Small reduction of activity."
FT                   /evidence="ECO:0000269|PubMed:12795596"
FT   MUTAGEN         360
FT                   /note="K->A,R: Almost no effect on activity."
FT                   /evidence="ECO:0000269|PubMed:12795596"
FT   CONFLICT        54
FT                   /note="G -> A (in Ref. 1; CAA49469)"
FT                   /evidence="ECO:0000305"
FT   STRAND          3..7
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           15..23
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          27..33
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           34..36
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           39..41
FT                   /evidence="ECO:0007829|PDB:1OX6"
FT   STRAND          45..49
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           53..62
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           66..74
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          79..83
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           84..87
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          90..93
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          104..111
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   TURN            114..116
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          119..125
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          143..150
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           155..163
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          167..173
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          176..184
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          187..193
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           194..196
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           198..209
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           221..227
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           232..235
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          240..248
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          250..252
FT                   /evidence="ECO:0007829|PDB:1OX5"
FT   STRAND          254..257
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           277..288
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          292..299
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           307..309
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           311..319
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   TURN            320..322
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          327..332
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           346..356
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          359..363
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           365..376
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           386..394
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           396..398
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          399..403
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          405..412
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           413..415
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          433..440
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   TURN            441..444
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          445..450
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           451..460
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          465..468
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           471..473
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   TURN            474..476
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           482..491
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          496..498
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           505..514
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   STRAND          518..523
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           524..527
FT                   /evidence="ECO:0007829|PDB:1JVN"
FT   HELIX           533..542
FT                   /evidence="ECO:0007829|PDB:1JVN"
SQ   SEQUENCE   552 AA;  61068 MW;  046E11EA5F83ABA3 CRC64;
     MPVVHVIDVE SGNLQSLTNA IEHLGYEVQL VKSPKDFNIS GTSRLILPGV GNYGHFVDNL
     FNRGFEKPIR EYIESGKPIM GICVGLQALF AGSVESPKST GLNYIDFKLS RFDDSEKPVP
     EIGWNSCIPS ENLFFGLDPY KRYYFVHSFA AILNSEKKKN LENDGWKIAK AKYGSEEFIA
     AVNKNNIFAT QFHPEKSGKA GLNVIENFLK QQSPPIPNYS AEEKELLMND YSNYGLTRRI
     IACLDVRTND QGDLVVTKGD QYDVREKSDG KGVRNLGKPV QLAQKYYQQG ADEVTFLNIT
     SFRDCPLKDT PMLEVLKQAA KTVFVPLTVG GGIKDIVDVD GTKIPALEVA SLYFRSGADK
     VSIGTDAVYA AEKYYELGNR GDGTSPIETI SKAYGAQAVV ISVDPKRVYV NSQADTKNKV
     FETEYPGPNG EKYCWYQCTI KGGRESRDLG VWELTRACEA LGAGEILLNC IDKDGSNSGY
     DLELIEHVKD AVKIPVIASS GAGVPEHFEE AFLKTRADAC LGAGMFHRGE FTVNDVKEYL
     LEHGLKVRMD EE
//
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