IMDH4_YEAST
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 03-AUG-2022, entry version 196.
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}; OrderedLocusNames=YML056C;
GN 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;
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 -!- 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}.
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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; 149.
DR DIP; DIP-6458N; -.
DR IntAct; P50094; 69.
DR MINT; P50094; -.
DR STRING; 4932.YML056C; -.
DR iPTMnet; P50094; -.
DR MaxQB; P50094; -.
DR PaxDb; P50094; -.
DR PRIDE; P50094; -.
DR EnsemblFungi; YML056C_mRNA; YML056C; YML056C.
DR GeneID; 854948; -.
DR KEGG; sce:YML056C; -.
DR SGD; S000004520; IMD4.
DR VEuPathDB; FungiDB:YML056C; -.
DR eggNOG; KOG2550; Eukaryota.
DR GeneTree; ENSGT00940000170207; -.
DR HOGENOM; CLU_022552_2_1_1; -.
DR OMA; GCTEESG; -.
DR BioCyc; YEAST:YML056C-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 UniPathway; UPA00601; UER00295.
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; 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; 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
