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 03-AUG-2022, entry version 187.
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; 14.
DR DIP; DIP-4222N; -.
DR MINT; P33734; -.
DR STRING; 4932.YBR248C; -.
DR iPTMnet; P33734; -.
DR MaxQB; P33734; -.
DR PaxDb; P33734; -.
DR PRIDE; P33734; -.
DR EnsemblFungi; YBR248C_mRNA; YBR248C; YBR248C.
DR GeneID; 852550; -.
DR KEGG; sce:YBR248C; -.
DR SGD; S000000452; HIS7.
DR VEuPathDB; FungiDB:YBR248C; -.
DR eggNOG; KOG0623; Eukaryota.
DR HOGENOM; CLU_037550_0_0_1; -.
DR InParanoid; P33734; -.
DR OMA; GHFGHCM; -.
DR BioCyc; YEAST:YBR248C-MON; -.
DR BRENDA; 4.3.1.B2; 984.
DR BRENDA; 4.3.2.10; 984.
DR SABIO-RK; P33734; -.
DR UniPathway; UPA00031; UER00010.
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; 3.20.20.70; -; 1.
DR Gene3D; 3.40.50.880; -; 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 Pfam; PF00117; GATase; 1.
DR Pfam; PF00977; His_biosynth; 1.
DR PIRSF; PIRSF036936; IGPS_HisHF; 1.
DR SUPFAM; SSF51366; SSF51366; 1.
DR SUPFAM; SSF52317; SSF52317; 1.
DR TIGRFAMs; TIGR00735; hisF; 1.
DR TIGRFAMs; TIGR01855; IMP_synth_hisH; 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
