ID   IMDH2_XENTR             Reviewed;         515 AA.
AC   F7CYY5;
DT   22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 1.
DT   27-MAR-2024, entry version 61.
DE   RecName: Full=Inosine-5'-monophosphate dehydrogenase 2 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMP dehydrogenase 2 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMPD 2 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            Short=IMPDH 2 {ECO:0000255|HAMAP-Rule:MF_03156};
DE            EC=1.1.1.205 {ECO:0000250|UniProtKB:P12268};
GN   Name=impdh2;
OS   Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX   NCBI_TaxID=8364;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=20431018; DOI=10.1126/science.1183670;
RA   Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA   Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA   Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA   Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA   Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA   Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA   Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA   Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA   Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT   "The genome of the Western clawed frog Xenopus tropicalis.";
RL   Science 328:633-636(2010).
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:0000250|UniProtKB:P12268}.
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:0000250|UniProtKB:P12268};
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:0000250|UniProtKB:P12268}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P12268}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P12268}. Nucleus
CC       {ECO:0000250|UniProtKB:P12268}. Cytoplasm, cytosol
CC       {ECO:0000250|UniProtKB:P12268}. Note=Can form fiber-like subcellular
CC       structures termed 'cytoophidia' in response to intracellular guanine-
CC       nucleotide depletion. {ECO:0000250|UniProtKB:P12268}.
CC   -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC       Rule:MF_03156}.
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DR   EMBL; AAMC01018809; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; F7CYY5; -.
DR   SMR; F7CYY5; -.
DR   STRING; 8364.ENSXETP00000043519; -.
DR   PaxDb; 8364-ENSXETP00000059998; -.
DR   AGR; Xenbase:XB-GENE-478728; -.
DR   eggNOG; KOG2550; Eukaryota.
DR   HOGENOM; CLU_022552_2_1_1; -.
DR   InParanoid; F7CYY5; -.
DR   UniPathway; UPA00601; UER00295.
DR   Proteomes; UP000008143; Genome assembly.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003938; F:IMP dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
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; ISS:UniProtKB.
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; 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:SF121; INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE 2; 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; SSF51412; Inosine monophosphate dehydrogenase (IMPDH); 2.
DR   PROSITE; PS51371; CBS; 2.
DR   PROSITE; PS00487; IMP_DH_GMP_RED; 1.
PE   3: Inferred from homology;
KW   CBS domain; Cytoplasm; GMP biosynthesis; Metal-binding; NAD; Nucleus;
KW   Oxidoreductase; Potassium; Purine biosynthesis; Reference proteome; Repeat.
FT   CHAIN           1..515
FT                   /note="Inosine-5'-monophosphate dehydrogenase 2"
FT                   /id="PRO_0000415679"
FT   DOMAIN          114..173
FT                   /note="CBS 1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   DOMAIN          179..238
FT                   /note="CBS 2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   ACT_SITE        332
FT                   /note="Thioimidate intermediate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   ACT_SITE        430
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         275..277
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         325..327
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         327
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         329
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         330
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
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         365..367
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         388..389
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         412..416
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         442
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         501
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         502
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         503
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"
SQ   SEQUENCE   515 AA;  55625 MW;  B99CBB519C5BA1DA CRC64;
     MADYLISGGT SYVPDDGLTA QQLFGAGDGL TYNDFLILPG YIDFTADQVD LTSALTKKIT
     LKTPMVSSPM DTVTEASMAI AMALTGGIGI MHHNCTPEFQ ANEVRKVKKY EQGFITDPVV
     LSPKHRVRDV FEAKARHGFC GIPITENGKM GSKLAGIISS RDIDFLKSEE HDLALSEIMT
     RREDLVVAPA GVTLKEANEI LQRSKKGKLL PIVNGNDELV AIIARTDLKK NRDYPLASKD
     AKKQLLCGAA IGTHEDDKYR LDLLVQAGVD AVVLDSSQGN SIFQINMIKF IKEKYQDLQV
     IAGNVVTAAQ AKNLIDAGAD ALRVGMGSGS ICITQEVLAC GRPQATAVYK VSEYARRFGV
     PVIADGGIQT VGHIAKALAL GASTVMMGSL LAATTEAPGE YFFSDGIRLK KYRGMGSLDA
     MDKNVSSQKR YFSEADKIKV AQGVSGAVQD KGSIHKFIPY LIAGIQHSCQ DIGAKSLTQV
     RAMMYSGELK FEKRTMSAQV EGGVHGLHSY EKRLF
//