ID   IMDH3_YEAST             Reviewed;         523 AA.
AC   P50095; D6VZ67;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 209.
DE   RecName: Full=Inosine-5'-monophosphate dehydrogenase 3 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMP dehydrogenase 3 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMPD 3 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMPDH 3 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            EC=1.1.1.205 {ECO:0000255|HAMAP-Rule:MF_03156};
GN   Name=IMD3 {ECO:0000255|HAMAP-Rule:MF_03156};
GN   OrderedLocusNames=YLR432W; ORFNames=L9753.4;
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 [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   [2]
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   [3]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14562095; DOI=10.1038/nature02026;
RA   Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA   Weissman J.S., O'Shea E.K.;
RT   "Global analysis of protein localization in budding yeast.";
RL   Nature 425:686-691(2003).
RN   [4]
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   [5]
RP   FUNCTION.
RX   PubMed=12746440; DOI=10.1074/jbc.m303736200;
RA   Hyle J.W., Shaw R.J., Reines D.;
RT   "Functional distinctions between IMP dehydrogenase genes in providing
RT   mycophenolate resistance and guanine prototrophy to yeast.";
RL   J. Biol. Chem. 278:28470-28478(2003).
RN   [6]
RP   FUNCTION, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=15292516; DOI=10.1073/pnas.0403341101;
RA   McPhillips C.C., Hyle J.W., Reines D.;
RT   "Detection of the mycophenolate-inhibited form of IMP dehydrogenase in
RT   vivo.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:12171-12176(2004).
RN   [7]
RP   FUNCTION, AND MUTAGENESIS OF ALA-253.
RX   PubMed=16278936; DOI=10.1002/yea.1300;
RA   Jenks M.H., Reines D.;
RT   "Dissection of the molecular basis of mycophenolate resistance in
RT   Saccharomyces cerevisiae.";
RL   Yeast 22:1181-1190(2005).
CC   -!- FUNCTION: Catalyzes the conversion of inosine 5'-phosphate (IMP) to
CC       xanthosine 5'-phosphate (XMP), the first committed and rate-limiting
CC       step in the de novo synthesis of guanine nucleotides, and therefore
CC       plays an important role in the regulation of cell growth.
CC       {ECO:0000255|HAMAP-Rule:MF_03156, ECO:0000269|PubMed:12746440,
CC       ECO:0000269|PubMed:15292516, ECO:0000269|PubMed:16278936}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + IMP + NAD(+) = H(+) + NADH + XMP; Xref=Rhea:RHEA:11708,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57464,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58053;
CC         EC=1.1.1.205; Evidence={ECO:0000255|HAMAP-Rule:MF_03156};
CC   -!- COFACTOR:
CC       Name=K(+); Xref=ChEBI:CHEBI:29103; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03156};
CC   -!- ACTIVITY REGULATION: Mycophenolic acid (MPA) is a non-competitive
CC       inhibitor that prevents formation of the closed enzyme conformation by
CC       binding to the same site as the amobile flap. In contrast, mizoribine
CC       monophosphate (MZP) is a competitive inhibitor that induces the closed
CC       conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor
CC       inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of
CC       bacterial IMPDH. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=100 uM for Inosine 5'-phosphate {ECO:0000269|PubMed:15292516};
CC         KM=314 uM for NAD(+) {ECO:0000269|PubMed:15292516};
CC   -!- PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP
CC       from IMP: step 1/1. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC   -!- SUBUNIT: Homotetramer. Seems to be able to form heterotetramers
CC       composed from more than 1 of the 3 IMPDH gene products (IMD2-4).
CC       {ECO:0000255|HAMAP-Rule:MF_03156, ECO:0000269|PubMed:15292516}.
CC   -!- INTERACTION:
CC       P50095; P50095: IMD3; NbExp=3; IntAct=EBI-9190, EBI-9190;
CC       P50095; P50094: IMD4; NbExp=8; IntAct=EBI-9190, EBI-9195;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03156,
CC       ECO:0000269|PubMed:14562095}.
CC   -!- MISCELLANEOUS: Present with 26300 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC       Rule:MF_03156}.
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DR   EMBL; U21094; AAB67516.1; -; Genomic_DNA.
DR   EMBL; BK006945; DAA09733.1; -; Genomic_DNA.
DR   PIR; S59402; S59402.
DR   RefSeq; NP_013536.3; NM_001182320.3.
DR   AlphaFoldDB; P50095; -.
DR   SMR; P50095; -.
DR   BioGRID; 31691; 218.
DR   DIP; DIP-1947N; -.
DR   IntAct; P50095; 199.
DR   MINT; P50095; -.
DR   STRING; 4932.YLR432W; -.
DR   iPTMnet; P50095; -.
DR   MaxQB; P50095; -.
DR   PaxDb; 4932-YLR432W; -.
DR   PeptideAtlas; P50095; -.
DR   EnsemblFungi; YLR432W_mRNA; YLR432W; YLR432W.
DR   GeneID; 851152; -.
DR   KEGG; sce:YLR432W; -.
DR   AGR; SGD:S000004424; -.
DR   SGD; S000004424; IMD3.
DR   VEuPathDB; FungiDB:YLR432W; -.
DR   eggNOG; KOG2550; Eukaryota.
DR   GeneTree; ENSGT00940000170207; -.
DR   HOGENOM; CLU_022552_2_1_1; -.
DR   InParanoid; P50095; -.
DR   OMA; MGYCGAK; -.
DR   OrthoDB; 166969at2759; -.
DR   BioCyc; YEAST:YLR432W-MONOMER; -.
DR   Reactome; R-SCE-6798695; Neutrophil degranulation.
DR   Reactome; R-SCE-73817; Purine ribonucleoside monophosphate biosynthesis.
DR   Reactome; R-SCE-9748787; Azathioprine ADME.
DR   SABIO-RK; P50095; -.
DR   UniPathway; UPA00601; UER00295.
DR   BioGRID-ORCS; 851152; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P50095; -.
DR   Proteomes; UP000002311; Chromosome XII.
DR   RNAct; P50095; Protein.
DR   GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR   GO; GO:0005886; C:plasma membrane; HDA:SGD.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0003938; F:IMP dehydrogenase activity; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0003729; F:mRNA binding; HDA:SGD.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-UniRule.
DR   GO; GO:0006183; P:GTP biosynthetic process; IBA:GO_Central.
DR   CDD; cd04601; CBS_pair_IMPDH; 1.
DR   CDD; cd00381; IMPDH; 1.
DR   Gene3D; 3.20.20.70; Aldolase class I; 1.
DR   HAMAP; MF_01964; IMPDH; 1.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR000644; CBS_dom.
DR   InterPro; IPR046342; CBS_dom_sf.
DR   InterPro; IPR005990; IMP_DH.
DR   InterPro; IPR015875; IMP_DH/GMP_Rdtase_CS.
DR   InterPro; IPR001093; IMP_DH_GMPRt.
DR   NCBIfam; TIGR01302; IMP_dehydrog; 1.
DR   PANTHER; PTHR11911:SF111; INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE; 1.
DR   PANTHER; PTHR11911; INOSINE-5-MONOPHOSPHATE DEHYDROGENASE RELATED; 1.
DR   Pfam; PF00571; CBS; 2.
DR   Pfam; PF00478; IMPDH; 1.
DR   PIRSF; PIRSF000130; IMPDH; 1.
DR   SMART; SM00116; CBS; 2.
DR   SMART; SM01240; IMPDH; 1.
DR   SUPFAM; SSF54631; CBS-domain pair; 1.
DR   SUPFAM; SSF51412; Inosine monophosphate dehydrogenase (IMPDH); 1.
DR   PROSITE; PS51371; CBS; 2.
DR   PROSITE; PS00487; IMP_DH_GMP_RED; 1.
PE   1: Evidence at protein level;
KW   CBS domain; Cytoplasm; GMP biosynthesis; Metal-binding; NAD;
KW   Oxidoreductase; Potassium; Purine biosynthesis; Reference proteome; Repeat.
FT   CHAIN           1..523
FT                   /note="Inosine-5'-monophosphate dehydrogenase 3"
FT                   /id="PRO_0000093683"
FT   DOMAIN          121..183
FT                   /note="CBS 1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   DOMAIN          184..240
FT                   /note="CBS 2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   ACT_SITE        335
FT                   /note="Thioimidate intermediate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   ACT_SITE        437
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         278..280
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         328..330
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         330
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /ligand_note="ligand shared between two tetrameric
FT                   partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         332
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /ligand_note="ligand shared between two tetrameric
FT                   partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         333
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         335
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /ligand_note="ligand shared between two tetrameric
FT                   partners"
FT                   /note="in other chain"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         368..370
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         391..392
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         415..419
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         449
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         508
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /ligand_note="ligand shared between two tetrameric
FT                   partners"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         509
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /ligand_note="ligand shared between two tetrameric
FT                   partners"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         510
FT                   /ligand="K(+)"
FT                   /ligand_id="ChEBI:CHEBI:29103"
FT                   /ligand_note="ligand shared between two tetrameric
FT                   partners"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   MUTAGEN         253
FT                   /note="A->S: Increases drug-resistance to MPA."
FT                   /evidence="ECO:0000269|PubMed:16278936"
SQ   SEQUENCE   523 AA;  56585 MW;  A0C84C22527AAEA6 CRC64;
     MAAVRDYKTA LEFAKSLPRL DGLSVQELMD SKTRGGLTYN DFLVLPGLVD FPSSEVSLQT
     KLTRNITLNT PFVSSPMDTV TESEMAIFMA LLGGIGFIHH NCTPEDQADM VRRVKNYENG
     FINNPIVISP TTTVGEAKSM KERFGFSGFP VTEDGKRNGK LMGIVTSRDI QFVEDNSLLV
     QDVMTKNPVT GAQGITLSEG NEILKKIKKG KLLIVDDNGN LVSMLSRTDL MKNQNYPLAS
     KSATTKQLLC GAAIGTIDAD KERLRLLVEA GLDVVILDSS QGNSIFQLNM IKWIKETFPD
     LEIIAGNVAT REQAANLIAA GADGLRIGMG SGSICITQEV MACGRPQGTA VYNVCEFANQ
     FGIPCMADGG VQNIGHITKA LALGSSTVMM GGMLAGTTES PGEYFYQDGK RLKAYRGMGS
     IDAMQKTGTK GNASTSRYFS ESDSVLVAQG VSGAVVDKGS IKKFIPYLYN GLQHSCQDIG
     YKSLTLLKEN VQSGKVRFEF RTASAQLEGG VHNLHSYEKR LHN
//