ID   IMDH4_YEAST             Reviewed;         524 AA.
AC   P50094; D6VZB8; Q2VQW8;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 203.
DE   RecName: Full=Inosine-5'-monophosphate dehydrogenase 4 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMP dehydrogenase 4 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMPD 4 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMPDH 4 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            EC=1.1.1.205 {ECO:0000255|HAMAP-Rule:MF_03156};
GN   Name=IMD4 {ECO:0000255|HAMAP-Rule:MF_03156};
GN   OrderedLocusNames=YML056C; ORFNames=YM9958.06C;
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=9169872;
RA   Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA   Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA   Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA   Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL   Nature 387:90-93(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   NUCLEOTIDE SEQUENCE [MRNA] OF 1-83.
RC   STRAIN=ATCC 208353 / W303-1A;
RX   PubMed=15905473; DOI=10.1093/nar/gki583;
RA   Zhang Z., Dietrich F.S.;
RT   "Mapping of transcription start sites in Saccharomyces cerevisiae using 5'
RT   SAGE.";
RL   Nucleic Acids Res. 33:2838-2851(2005).
RN   [4]
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   [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   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   [7]
RP   FUNCTION, AND SUBUNIT.
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   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, AND IDENTIFICATION BY
RP   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).
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}.
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   -!- 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       P50094; P50095: IMD3; NbExp=8; IntAct=EBI-9195, EBI-9190;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03156,
CC       ECO:0000269|PubMed:14562095}.
CC   -!- MISCELLANEOUS: Present with 2970 molecules/cell in log phase SD medium.
CC       {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; Z46729; CAA86719.1; -; Genomic_DNA.
DR   EMBL; AY899250; AAX83935.1; -; mRNA.
DR   EMBL; BK006946; DAA09842.1; -; Genomic_DNA.
DR   PIR; S50890; S50890.
DR   RefSeq; NP_013656.1; NM_001182414.1.
DR   AlphaFoldDB; P50094; -.
DR   SMR; P50094; -.
DR   BioGRID; 35111; 156.
DR   DIP; DIP-6458N; -.
DR   IntAct; P50094; 69.
DR   MINT; P50094; -.
DR   STRING; 4932.YML056C; -.
DR   iPTMnet; P50094; -.
DR   MaxQB; P50094; -.
DR   PaxDb; 4932-YML056C; -.
DR   PeptideAtlas; P50094; -.
DR   EnsemblFungi; YML056C_mRNA; YML056C; YML056C.
DR   GeneID; 854948; -.
DR   KEGG; sce:YML056C; -.
DR   AGR; SGD:S000004520; -.
DR   SGD; S000004520; IMD4.
DR   VEuPathDB; FungiDB:YML056C; -.
DR   eggNOG; KOG2550; Eukaryota.
DR   GeneTree; ENSGT00940000170207; -.
DR   HOGENOM; CLU_022552_2_1_1; -.
DR   InParanoid; P50094; -.
DR   OMA; NCPPDEQ; -.
DR   OrthoDB; 166969at2759; -.
DR   BioCyc; YEAST:YML056C-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   UniPathway; UPA00601; UER00295.
DR   BioGRID-ORCS; 854948; 2 hits in 10 CRISPR screens.
DR   PRO; PR:P50094; -.
DR   Proteomes; UP000002311; Chromosome XIII.
DR   RNAct; P50094; Protein.
DR   GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR   GO; GO:0003938; F:IMP dehydrogenase activity; ISS:SGD.
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; Phosphoprotein; Potassium; Purine biosynthesis;
KW   Reference proteome; Repeat.
FT   CHAIN           1..524
FT                   /note="Inosine-5'-monophosphate dehydrogenase 4"
FT                   /id="PRO_0000093684"
FT   DOMAIN          122..183
FT                   /note="CBS 1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   DOMAIN          185..241
FT                   /note="CBS 2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   ACT_SITE        336
FT                   /note="Thioimidate intermediate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   ACT_SITE        438
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         279..281
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         329..331
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         331
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="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         334
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         336
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         369..371
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         392..393
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         416..420
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         450
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
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   BINDING         511
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   MOD_RES         125
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
SQ   SEQUENCE   524 AA;  56394 MW;  A73D1E4EFE8AEAD9 CRC64;
     MSAAPLDYKK ALEHLKTYSS KDGLSVQELM DSTTRGGLTY NDFLVLPGLV NFPSSAVSLQ
     TKLTKKITLN TPFVSSPMDT VTEADMAIYM ALLGGIGFIH HNCTPKEQAS MVKKVKMFEN
     GFINSPIVIS PTTTVGEVKV MKRKFGFSGF PVTEDGKCPG KLVGLVTSRD IQFLEDDSLV
     VSEVMTKNPV TGIKGITLKE GNEILKQTKK GKLLIVDDNG NLVSMLSRAD LMKNQNYPLA
     SKSATTKQLL CGAAIGTIEA DKERLRLLVE AGLDVVILDS SQGNSVFQLN MIKWIKETFP
     DLEIIAGNVA TREQAANLIA AGADGLRIGM GSGSICITQE VMACGRPQGT AVYNVCQFAN
     QFGVPCMADG GVQNIGHITK ALALGSSTVM MGGMLAGTTE SPGEYFYKDG KRLKAYRGMG
     SIDAMQKTGN KGNASTSRYF SESDSVLVAQ GVSGAVVDKG SIKKFIPYLY NGLQHSCQDI
     GCESLTSLKE NVQNGEVRFE FRTASAQLEG GVHNLHSYEK RLYN
//