IMDH2_MOUSE
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 03-AUG-2022, entry version 203.
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, Pancreas,
RC 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;
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: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; 17.
DR IntAct; P24547; 3.
DR MINT; P24547; -.
DR STRING; 10090.ENSMUSP00000079888; -.
DR BindingDB; P24547; -.
DR ChEMBL; CHEMBL3169; -.
DR iPTMnet; P24547; -.
DR PhosphoSitePlus; P24547; -.
DR SwissPalm; P24547; -.
DR REPRODUCTION-2DPAGE; P24547; -.
DR EPD; P24547; -.
DR jPOST; P24547; -.
DR PaxDb; P24547; -.
DR PeptideAtlas; P24547; -.
DR PRIDE; P24547; -.
DR ProteomicsDB; 269310; -.
DR Antibodypedia; 30367; 399 antibodies from 38 providers.
DR DNASU; 23918; -.
DR Ensembl; ENSMUST00000081111; ENSMUSP00000079888; ENSMUSG00000062867.
DR GeneID; 23918; -.
DR KEGG; mmu:23918; -.
DR UCSC; uc009rqg.1; mouse.
DR CTD; 3615; -.
DR MGI; MGI:109367; Impdh2.
DR VEuPathDB; HostDB:ENSMUSG00000062867; -.
DR eggNOG; KOG2550; Eukaryota.
DR GeneTree; ENSGT00940000157726; -.
DR InParanoid; P24547; -.
DR OMA; HDYHMTL; -.
DR OrthoDB; 618077at2759; -.
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 74 CRISPR screens.
DR ChiTaRS; Impdh2; mouse.
DR PRO; PR:P24547; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P24547; protein.
DR Bgee; ENSMUSG00000062867; Expressed in morula and 99 other tissues.
DR ExpressionAtlas; P24547; baseline and differential.
DR Genevisible; P24547; MM.
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 GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl.
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; 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 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 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
