IMDH3_YEAST
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 03-AUG-2022, entry version 203.
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}; OrderedLocusNames=YLR432W;
GN 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;
CC Evidence={ECO:0000255|HAMAP-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}.
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; 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; 207.
DR DIP; DIP-1947N; -.
DR IntAct; P50095; 199.
DR MINT; P50095; -.
DR STRING; 4932.YLR432W; -.
DR iPTMnet; P50095; -.
DR MaxQB; P50095; -.
DR PaxDb; P50095; -.
DR PRIDE; P50095; -.
DR EnsemblFungi; YLR432W_mRNA; YLR432W; YLR432W.
DR GeneID; 851152; -.
DR KEGG; sce:YLR432W; -.
DR SGD; S000004424; IMD3.
DR VEuPathDB; FungiDB:YLR432W; -.
DR eggNOG; KOG2550; Eukaryota.
DR GeneTree; ENSGT00940000170207; -.
DR HOGENOM; CLU_022552_2_1_1; -.
DR OMA; MGYCGAK; -.
DR BioCyc; YEAST:YLR432W-MON; -.
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 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; cd00381; IMPDH; 1.
DR Gene3D; 3.20.20.70; -; 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 PANTHER; PTHR11911; PTHR11911; 1.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00478; IMPDH; 1.
DR PIRSF; PIRSF000130; IMPDH; 1.
DR SMART; SM00116; CBS; 2.
DR SUPFAM; SSF54631; SSF54631; 1.
DR TIGRFAMs; TIGR01302; IMP_dehydrog; 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
