ID   IMDH2_MOUSE             Reviewed;         514 AA.
AC   P24547; Q61734; Q91Z11;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2003, sequence version 2.
DT   27-MAR-2024, entry version 212.
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};
DE   AltName: Full=IMPDH-II;
GN   Name=Impdh2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1671845; DOI=10.1016/0378-1119(91)90065-j;
RA   Tiedeman A.A., Smith J.M.;
RT   "Isolation and sequence of a cDNA encoding mouse IMP dehydrogenase.";
RL   Gene 97:289-293(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS MYCOPHENOLIC ACID RESISTANT.
RC   TISSUE=Brain;
RX   PubMed=7906545; DOI=10.1016/0167-4781(94)90029-9;
RA   Lightfoot T., Snyder F.F.;
RT   "Gene amplification and dual point mutations of mouse IMP dehydrogenase
RT   associated with cellular resistance to mycophenolic acid.";
RL   Biochim. Biophys. Acta 1217:156-162(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C3H/He, and Czech II; TISSUE=Mammary gland, and Osteoblast;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   PROTEIN SEQUENCE OF 125-133; 182-194; 289-290; 439-449; 456-466 AND
RP   475-478.
RX   PubMed=2572589; DOI=10.1016/s0021-9258(19)84687-2;
RA   Hodges S.D., Fung E., McKay D.J., Renaux B.S., Snyder F.F.;
RT   "Increased activity, amount, and altered kinetic properties of IMP
RT   dehydrogenase from mycophenolic acid-resistant neuroblastoma cells.";
RL   J. Biol. Chem. 264:18137-18141(1989).
RN   [5]
RP   PROTEIN SEQUENCE OF 137-149.
RC   TISSUE=Brain;
RA   Lubec G., Yang J.W., Zigmond M.;
RL   Submitted (JUL-2007) to UniProtKB.
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(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. Could also
CC       have a single-stranded nucleic acid-binding activity and could play a
CC       role in RNA and/or DNA metabolism. It may also have a role in the
CC       development of malignancy and the growth progression of some tumors.
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. Interacts with CLOCK; in a circadian manner.
CC       Interacts with ANKRD9; leading to its ubiquitination and degradation by
CC       the proteasome. {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   -!- PTM: Acetylated by CLOCK in a circadian manner.
CC       {ECO:0000250|UniProtKB:P12268}.
CC   -!- PTM: Ubiquitinated leading to its degradation by the proteasome.
CC       {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; M33934; AAA39311.1; -; mRNA.
DR   EMBL; M98333; AAA20181.1; -; mRNA.
DR   EMBL; BC010314; AAH10314.1; -; mRNA.
DR   EMBL; BC052671; AAH52671.1; -; mRNA.
DR   CCDS; CCDS40768.1; -.
DR   PIR; JT0565; JT0565.
DR   RefSeq; NP_035960.2; NM_011830.3.
DR   AlphaFoldDB; P24547; -.
DR   SMR; P24547; -.
DR   BioGRID; 204792; 19.
DR   IntAct; P24547; 3.
DR   MINT; P24547; -.
DR   STRING; 10090.ENSMUSP00000079888; -.
DR   BindingDB; P24547; -.
DR   ChEMBL; CHEMBL3169; -.
DR   GlyGen; P24547; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P24547; -.
DR   PhosphoSitePlus; P24547; -.
DR   SwissPalm; P24547; -.
DR   REPRODUCTION-2DPAGE; P24547; -.
DR   EPD; P24547; -.
DR   jPOST; P24547; -.
DR   PaxDb; 10090-ENSMUSP00000079888; -.
DR   PeptideAtlas; P24547; -.
DR   ProteomicsDB; 269310; -.
DR   Pumba; P24547; -.
DR   Antibodypedia; 30367; 449 antibodies from 38 providers.
DR   DNASU; 23918; -.
DR   Ensembl; ENSMUST00000081111.14; ENSMUSP00000079888.9; ENSMUSG00000062867.14.
DR   GeneID; 23918; -.
DR   KEGG; mmu:23918; -.
DR   UCSC; uc009rqg.1; mouse.
DR   AGR; MGI:109367; -.
DR   CTD; 3615; -.
DR   MGI; MGI:109367; Impdh2.
DR   VEuPathDB; HostDB:ENSMUSG00000062867; -.
DR   eggNOG; KOG2550; Eukaryota.
DR   GeneTree; ENSGT00940000157726; -.
DR   InParanoid; P24547; -.
DR   OMA; GSHCTTR; -.
DR   OrthoDB; 166969at2759; -.
DR   PhylomeDB; P24547; -.
DR   TreeFam; TF300378; -.
DR   BRENDA; 1.1.1.205; 3474.
DR   Reactome; R-MMU-6798695; Neutrophil degranulation.
DR   Reactome; R-MMU-73817; Purine ribonucleoside monophosphate biosynthesis.
DR   Reactome; R-MMU-9748787; Azathioprine ADME.
DR   UniPathway; UPA00601; UER00295.
DR   BioGRID-ORCS; 23918; 26 hits in 79 CRISPR screens.
DR   ChiTaRS; Impdh2; mouse.
DR   PRO; PR:P24547; -.
DR   Proteomes; UP000000589; Chromosome 9.
DR   RNAct; P24547; Protein.
DR   Bgee; ENSMUSG00000062867; Expressed in blastoderm cell in morula and 102 other cell types or tissues.
DR   ExpressionAtlas; P24547; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0003938; F:IMP dehydrogenase activity; IDA:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0000166; F:nucleotide binding; ISS:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0097294; P:'de novo' XMP biosynthetic process; IMP:MGI.
DR   GO; GO:0071353; P:cellular response to interleukin-4; IDA:MGI.
DR   GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR   GO; GO:0006177; P:GMP biosynthetic process; IDA:MGI.
DR   GO; GO:0032263; P:GMP salvage; TAS:MGI.
DR   GO; GO:0006183; P:GTP biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0046651; P:lymphocyte proliferation; IMP:MGI.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; IMP:MGI.
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.
DR   Genevisible; P24547; MM.
PE   1: Evidence at protein level;
KW   Acetylation; CBS domain; Cytoplasm; Direct protein sequencing; DNA-binding;
KW   GMP biosynthesis; Isopeptide bond; Metal-binding; NAD; Nucleus;
KW   Oxidoreductase; Phosphoprotein; Potassium; Purine biosynthesis;
KW   Reference proteome; Repeat; RNA-binding; Ubl conjugation.
FT   CHAIN           1..514
FT                   /note="Inosine-5'-monophosphate dehydrogenase 2"
FT                   /id="PRO_0000093674"
FT   DOMAIN          114..173
FT                   /note="CBS 1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   DOMAIN          179..237
FT                   /note="CBS 2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   ACT_SITE        331
FT                   /note="Thioimidate intermediate"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   ACT_SITE        429
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         274..276
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         324..326
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         326
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         328
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="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
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         364..366
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         387..388
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         411..415
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         441
FT                   /ligand="IMP"
FT                   /ligand_id="ChEBI:CHEBI:58053"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT   BINDING         500
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         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   MOD_RES         122
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P12268"
FT   MOD_RES         160
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P12268"
FT   MOD_RES         400
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P12268"
FT   MOD_RES         416
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         511
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P12268"
FT   CROSSLNK        195
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P12268"
FT   CROSSLNK        208
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P12268"
FT   CROSSLNK        438
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0000250|UniProtKB:P12268"
FT   VARIANT         333
FT                   /note="T -> I (in mycophenolic acid resistant cells)"
FT   VARIANT         351
FT                   /note="S -> Y (in mycophenolic acid resistant cells)"
FT   CONFLICT        458
FT                   /note="P -> L (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        465
FT                   /note="Q -> S (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        483
FT                   /note="M -> T (in Ref. 1; AAA39311)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   514 AA;  55815 MW;  17D25A5C5EBCC439 CRC64;
     MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD LTSALTKKIT
     LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ ANEVRKVKKY EQGFITDPVV
     LSPKDRVRDV FEAKARHGFC GIPITDTGRM GSRLVGIISS RDIDFLKEEE HDRFLEEIMT
     KREDLVVAPA GVTLKEANEI LQRSKKGKLP IVNENDELVA IIARTDLKKN RDYPLASKDA
     KKQLLCGAAI GTHEDDKYRL DLLALAGVDV VVLDSSQGNS IFQINMIKYI KEKYPSLQVI
     GGNVVTAAQA KNLIDAGVDA LRVGMGSGSI CITQEVLACG RPQATAVYKV SEYARRFGVP
     VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY FFSDGIRLKK YRGMGSLDAM
     DKHLSSQNRY FSEADKIKVA QGVSGAVQDK GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR
     AMMYSGELKF EKRTSSAQVE GGVHSLHSYE KRLF
//