ID   PUR91_YEAST             Reviewed;         591 AA.
AC   P54113; D6VY30; E9PAG6;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 187.
DE   RecName: Full=Bifunctional purine biosynthesis protein ADE16;
DE   Includes:
DE     RecName: Full=Phosphoribosylaminoimidazolecarboxamide formyltransferase;
DE              EC=2.1.2.3 {ECO:0000269|PubMed:10877846, ECO:0000305|PubMed:9143321};
DE     AltName: Full=5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase {ECO:0000303|PubMed:9143321};
DE     AltName: Full=AICAR transformylase {ECO:0000303|PubMed:9143321};
DE   Includes:
DE     RecName: Full=Inosine 5'-monophosphate cyclohydrolase {ECO:0000305};
DE              Short=IMP cyclohydrolase {ECO:0000303|PubMed:9143321};
DE              EC=3.5.4.10 {ECO:0000269|PubMed:10877846, ECO:0000305|PubMed:9143321};
DE     AltName: Full=ATIC;
DE     AltName: Full=IMP synthase;
DE     AltName: Full=Inosinicase;
GN   Name=ADE16 {ECO:0000303|PubMed:9143321}; OrderedLocusNames=YLR028C;
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], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP   AND DISRUPTION PHENOTYPE.
RX   PubMed=9143321; DOI=10.1006/abbi.1997.9919;
RA   Tibbetts A.S., Appling D.R.;
RT   "Saccharomyces cerevisiae expresses two genes encoding isozymes of 5-
RT   aminoimidazole-4-carboxamide ribonucleotide transformylase.";
RL   Arch. Biochem. Biophys. 340:195-200(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169871;
RA   Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA   Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA   Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA   Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA   Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA   Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA   Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA   Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA   Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA   Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA   Zollner A., Hani J., Hoheisel J.D.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL   Nature 387:87-90(1997).
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   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY,
RP   SUBUNIT, SUBCELLULAR LOCATION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=10877846; DOI=10.1074/jbc.m909851199;
RA   Tibbetts A.S., Appling D.R.;
RT   "Characterization of two 5-aminoimidazole-4-carboxamide ribonucleotide
RT   transformylase/inosine monophosphate cyclohydrolase isozymes from
RT   Saccharomyces cerevisiae.";
RL   J. Biol. Chem. 275:20920-20927(2000).
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).
CC   -!- FUNCTION: Bifunctional enzyme that catalyzes the last two steps of
CC       purine biosynthesis (PubMed:9143321, PubMed:10877846). Acts as a
CC       transformylase that incorporates a formyl group to the AMP analog AICAR
CC       (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to
CC       produce the intermediate formyl-AICAR (FAICAR) (PubMed:9143321,
CC       PubMed:10877846). Also catalyzes the cyclization of FAICAR to IMP
CC       (PubMed:9143321, PubMed:10877846). {ECO:0000269|PubMed:10877846,
CC       ECO:0000269|PubMed:9143321}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(6R)-10-formyltetrahydrofolate + 5-amino-1-(5-phospho-beta-D-
CC         ribosyl)imidazole-4-carboxamide = (6S)-5,6,7,8-tetrahydrofolate + 5-
CC         formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide;
CC         Xref=Rhea:RHEA:22192, ChEBI:CHEBI:57453, ChEBI:CHEBI:58467,
CC         ChEBI:CHEBI:58475, ChEBI:CHEBI:195366; EC=2.1.2.3;
CC         Evidence={ECO:0000269|PubMed:10877846, ECO:0000305|PubMed:9143321};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + IMP = 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-
CC         carboxamide; Xref=Rhea:RHEA:18445, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:58053, ChEBI:CHEBI:58467; EC=3.5.4.10;
CC         Evidence={ECO:0000269|PubMed:10877846, ECO:0000305|PubMed:9143321};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=26 uM for
CC         5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide (with
CC         (6S)-10-formyltetrahydrofolate as cosubstrate) (at pH 7.4)
CC         {ECO:0000269|PubMed:10877846};
CC         KM=131 uM for (6S)-10-formyltetrahydrofolate (with
CC         5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide as
CC         cosubstrate) (at pH 7.4) {ECO:0000269|PubMed:10877846};
CC   -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; 5-
CC       formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide from 5-amino-
CC       1-(5-phospho-D-ribosyl)imidazole-4-carboxamide (10-formyl THF route):
CC       step 1/1. {ECO:0000269|PubMed:10877846, ECO:0000269|PubMed:9143321}.
CC   -!- PATHWAY: Purine metabolism; IMP biosynthesis via de novo pathway; IMP
CC       from 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide: step
CC       1/1. {ECO:0000269|PubMed:10877846, ECO:0000269|PubMed:9143321}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10877846}.
CC   -!- INTERACTION:
CC       P54113; P38009: ADE17; NbExp=5; IntAct=EBI-14213, EBI-14223;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10877846}.
CC   -!- INDUCTION: Induced during growth on the non-fermentable carbon source
CC       glycerol with ethanol (PubMed:10877846). Does not appear to be
CC       repressed by adenine (PubMed:10877846). {ECO:0000269|PubMed:10877846}.
CC   -!- DOMAIN: The IMP cyclohydrolase activity resides in the N-terminal
CC       region. {ECO:0000250|UniProtKB:P31939}.
CC   -!- DISRUPTION PHENOTYPE: Simultaneous knockout of ADE17 leads to adenine
CC       and histidine auxotrophy. {ECO:0000269|PubMed:10877846,
CC       ECO:0000269|PubMed:9143321}.
CC   -!- MISCELLANEOUS: Present with 7700 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the PurH family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA97551.2; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305};
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DR   EMBL; U62402; AAB57774.1; -; Genomic_DNA.
DR   EMBL; Z73199; CAA97551.2; ALT_SEQ; Genomic_DNA.
DR   EMBL; Z73200; CAA97552.1; -; Genomic_DNA.
DR   EMBL; BK006945; DAA09346.1; -; Genomic_DNA.
DR   PIR; S77707; S77707.
DR   RefSeq; NP_013128.1; NM_001181915.1.
DR   AlphaFoldDB; P54113; -.
DR   SMR; P54113; -.
DR   BioGRID; 31302; 191.
DR   DIP; DIP-4657N; -.
DR   IntAct; P54113; 17.
DR   MINT; P54113; -.
DR   STRING; 4932.YLR028C; -.
DR   CarbonylDB; P54113; -.
DR   iPTMnet; P54113; -.
DR   MaxQB; P54113; -.
DR   PaxDb; 4932-YLR028C; -.
DR   PeptideAtlas; P54113; -.
DR   TopDownProteomics; P54113; -.
DR   EnsemblFungi; YLR028C_mRNA; YLR028C; YLR028C.
DR   GeneID; 850715; -.
DR   KEGG; sce:YLR028C; -.
DR   AGR; SGD:S000004018; -.
DR   SGD; S000004018; ADE16.
DR   VEuPathDB; FungiDB:YLR028C; -.
DR   eggNOG; KOG2555; Eukaryota.
DR   GeneTree; ENSGT00390000004553; -.
DR   HOGENOM; CLU_016316_3_2_1; -.
DR   InParanoid; P54113; -.
DR   OMA; GKHPGKI; -.
DR   OrthoDB; 275312at2759; -.
DR   BioCyc; MetaCyc:YLR028C-MONOMER; -.
DR   BioCyc; YEAST:YLR028C-MONOMER; -.
DR   UniPathway; UPA00074; UER00133.
DR   UniPathway; UPA00074; UER00135.
DR   BioGRID-ORCS; 850715; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P54113; -.
DR   Proteomes; UP000002311; Chromosome XII.
DR   RNAct; P54113; Protein.
DR   GO; GO:0005829; C:cytosol; IDA:SGD.
DR   GO; GO:0003937; F:IMP cyclohydrolase activity; IDA:SGD.
DR   GO; GO:0004643; F:phosphoribosylaminoimidazolecarboxamide formyltransferase activity; IDA:SGD.
DR   GO; GO:0006189; P:'de novo' IMP biosynthetic process; IDA:SGD.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; IDA:SGD.
DR   CDD; cd01421; IMPCH; 1.
DR   Gene3D; 1.10.287.440; -; 1.
DR   Gene3D; 3.40.140.20; -; 2.
DR   Gene3D; 3.40.50.1380; Methylglyoxal synthase-like domain; 1.
DR   HAMAP; MF_00139; PurH; 1.
DR   InterPro; IPR024051; AICAR_Tfase_dup_dom_sf.
DR   InterPro; IPR024050; AICAR_Tfase_insert_dom_sf.
DR   InterPro; IPR016193; Cytidine_deaminase-like.
DR   InterPro; IPR011607; MGS-like_dom.
DR   InterPro; IPR036914; MGS-like_dom_sf.
DR   InterPro; IPR002695; PurH-like.
DR   NCBIfam; TIGR00355; purH; 1.
DR   PANTHER; PTHR11692:SF0; BIFUNCTIONAL PURINE BIOSYNTHESIS PROTEIN ATIC; 1.
DR   PANTHER; PTHR11692; BIFUNCTIONAL PURINE BIOSYNTHESIS PROTEIN PURH; 1.
DR   Pfam; PF01808; AICARFT_IMPCHas; 1.
DR   Pfam; PF02142; MGS; 1.
DR   PIRSF; PIRSF000414; AICARFT_IMPCHas; 1.
DR   SMART; SM00798; AICARFT_IMPCHas; 1.
DR   SMART; SM00851; MGS; 1.
DR   SUPFAM; SSF53927; Cytidine deaminase-like; 1.
DR   SUPFAM; SSF52335; Methylglyoxal synthase-like; 1.
DR   PROSITE; PS51855; MGS; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Hydrolase; Multifunctional enzyme; Purine biosynthesis;
KW   Reference proteome; Transferase.
FT   CHAIN           1..591
FT                   /note="Bifunctional purine biosynthesis protein ADE16"
FT                   /id="PRO_0000192159"
FT   DOMAIN          1..147
FT                   /note="MGS-like"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01202"
FT   ACT_SITE        138
FT                   /note="Proton donor/acceptor; for FAICAR cyclization
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   ACT_SITE        267
FT                   /note="Proton acceptor; for AICAR formyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         35..38
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         65..68
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         102..103
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         126..127
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         206..207
FT                   /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
FT                   carboxamide"
FT                   /ligand_id="ChEBI:CHEBI:58475"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         267
FT                   /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
FT                   carboxamide"
FT                   /ligand_id="ChEBI:CHEBI:58475"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         315
FT                   /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
FT                   carboxamide"
FT                   /ligand_id="ChEBI:CHEBI:58475"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         338
FT                   /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
FT                   carboxamide"
FT                   /ligand_id="ChEBI:CHEBI:58475"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         430
FT                   /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
FT                   carboxamide"
FT                   /ligand_id="ChEBI:CHEBI:58475"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         450
FT                   /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
FT                   carboxamide"
FT                   /ligand_id="ChEBI:CHEBI:58475"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         451
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P31335"
FT   BINDING         540
FT                   /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
FT                   carboxamide"
FT                   /ligand_id="ChEBI:CHEBI:58475"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   BINDING         545
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P31335"
FT   BINDING         564..565
FT                   /ligand="(6R)-10-formyltetrahydrofolate"
FT                   /ligand_id="ChEBI:CHEBI:195366"
FT                   /evidence="ECO:0000250|UniProtKB:P31335"
FT   BINDING         587
FT                   /ligand="5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-
FT                   carboxamide"
FT                   /ligand_id="ChEBI:CHEBI:58475"
FT                   /ligand_note="ligand shared between dimeric partners"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
FT   SITE            266
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000250|UniProtKB:P31939"
SQ   SEQUENCE   591 AA;  65282 MW;  DEC06684BFED7CA7 CRC64;
     MGKYTKTAIL SVYDKTGLLD LAKGLVENNV RILASGGTAN MVREAGFPVD DVSSITHAPE
     MLGGRVKTLH PAVHAGILAR NLEGDEKDLK EQHIDKVDFV VCNLYPFKET VAKIGVTVQE
     AVEEIDIGGV TLLRAAAKNH SRVTILSDPN DYSIFLQDLS KDGEISQDLR NRFALKAFEH
     TADYDAAISD FFRKQYSEGK AQLPLRYGCN PHQRPAQAYI TQQEELPFKV LCGTPGYINL
     LDALNSWPLV KELSASLNLP AAASFKHVSP AGAAVGLPLS DVERQVYFVN DMEDLSPLAC
     AYARARGADR MSSFGDFIAL SNIVDVATAK IISKEVSDGV IAPGYEPEAL NILSKKKNGK
     YCILQIDPNY VPGQMESREV FGVTLQQKRN DAIINQSTFK EIVSKNKALT EQAVIDLTVA
     TLVLKYTQSN SVCYAKNGMV VGLGAGQQSR IHCTRLAGDK TDNWWLRQHP KVLNMKWAKG
     IKRADKSNAI DLFVTGQRIE GPEKVDYESK FEEVPEPFTK EERLEWLSKL NNVSLSSDAF
     FPFPDNVYRA VQSGVKFITA PSGSVMDKVV FQAADSFDIV YVENPIRLFH H
//