IMDH1_MOUSE
ID IMDH1_MOUSE Reviewed; 514 AA.
AC P50096; Q7TSG7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Inosine-5'-monophosphate dehydrogenase 1 {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMP dehydrogenase 1 {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMPD 1 {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMPDH 1 {ECO:0000255|HAMAP-Rule:MF_03156};
DE EC=1.1.1.205 {ECO:0000255|HAMAP-Rule:MF_03156};
DE AltName: Full=IMPDH-I;
GN Name=Impdh1;
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].
RC TISSUE=Leukemia;
RX PubMed=7690562; DOI=10.1006/bbrc.1993.2129;
RA Dayton J.S., Mitchell B.S.;
RT "Type I inosine monophosphate dehydrogenase: evidence for a single
RT functional gene in mammalian species.";
RL Biochem. Biophys. Res. Commun. 195:897-901(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Lung, Pancreas, and Spleen;
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).
RN [6]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-341 AND ARG-355, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
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:0000255|HAMAP-Rule:MF_03156}.
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.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03156}.
CC Nucleus {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC Rule:MF_03156}.
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DR EMBL; U00978; AAA18285.1; -; mRNA.
DR EMBL; AK171139; BAE42272.1; -; mRNA.
DR EMBL; CH466533; EDL13790.1; -; Genomic_DNA.
DR EMBL; BC053416; AAH53416.1; -; mRNA.
DR CCDS; CCDS39449.1; -.
DR RefSeq; NP_001289862.1; NM_001302933.1.
DR RefSeq; NP_001289863.1; NM_001302934.1.
DR RefSeq; NP_035959.2; NM_011829.3.
DR AlphaFoldDB; P50096; -.
DR SMR; P50096; -.
DR BioGRID; 204791; 33.
DR IntAct; P50096; 1.
DR STRING; 10090.ENSMUSP00000077289; -.
DR iPTMnet; P50096; -.
DR PhosphoSitePlus; P50096; -.
DR EPD; P50096; -.
DR MaxQB; P50096; -.
DR PaxDb; P50096; -.
DR PRIDE; P50096; -.
DR ProteomicsDB; 267244; -.
DR Antibodypedia; 17770; 284 antibodies from 33 providers.
DR DNASU; 23917; -.
DR Ensembl; ENSMUST00000078155; ENSMUSP00000077289; ENSMUSG00000003500.
DR Ensembl; ENSMUST00000159124; ENSMUSP00000124931; ENSMUSG00000003500.
DR Ensembl; ENSMUST00000162099; ENSMUSP00000124541; ENSMUSG00000003500.
DR GeneID; 23917; -.
DR KEGG; mmu:23917; -.
DR UCSC; uc009bda.2; mouse.
DR CTD; 3614; -.
DR MGI; MGI:96567; Impdh1.
DR VEuPathDB; HostDB:ENSMUSG00000003500; -.
DR eggNOG; KOG2550; Eukaryota.
DR GeneTree; ENSGT00940000154156; -.
DR InParanoid; P50096; -.
DR OMA; MGYCGAK; -.
DR OrthoDB; 618077at2759; -.
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; 23917; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Impdh1; mouse.
DR PRO; PR:P50096; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P50096; protein.
DR Bgee; ENSMUSG00000003500; Expressed in retinal neural layer and 197 other tissues.
DR ExpressionAtlas; P50096; baseline and differential.
DR Genevisible; P50096; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
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:0003676; F:nucleic acid binding; ISS:UniProtKB.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0097294; P:'de novo' XMP biosynthetic process; IMP:MGI.
DR GO; GO:0006177; P:GMP biosynthetic process; IMP:MGI.
DR GO; GO:0032263; P:GMP salvage; TAS:MGI.
DR GO; GO:0006183; P:GTP biosynthetic process; IBA:GO_Central.
DR GO; GO:0046651; P:lymphocyte proliferation; IMP:MGI.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; IMP:MGI.
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 CBS domain; Cytoplasm; GMP biosynthesis; Metal-binding; Methylation; NAD;
KW Nucleus; Oxidoreductase; Phosphoprotein; Potassium; Purine biosynthesis;
KW Reference proteome; Repeat.
FT CHAIN 1..514
FT /note="Inosine-5'-monophosphate dehydrogenase 1"
FT /id="PRO_0000093671"
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 160
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20839"
FT MOD_RES 341
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 355
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CONFLICT 21..22
FT /note="QQ -> HE (in Ref. 1; AAA18285)"
FT /evidence="ECO:0000305"
FT CONFLICT 273
FT /note="L -> H (in Ref. 1; AAA18285)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="M -> I (in Ref. 1; AAA18285)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 514 AA; 55279 MW; 69E2DD40F03701F2 CRC64;
MADYLISGGT GYVPEDGLTA QQLFANADGL TYNDFLILPG FIDFIADEVD LTSALTRKIT
LKTPLISSPM DTVTEADMAI AMALMGGIGF IHHNCTPEFQ ANEVRKVKKF EQGFITDPVV
LSPSHTVGDV LEAKIQHGFS GIPITATGTM GSKLVGIVTS RDIDFLAEKD HTTLLSEVMT
PRVELVVAPA GVTLKEANEI LQRSKKGKLP IVNDQDELVA IIARTDLKKN RDYPLASKDS
HKQLLCGAAV GTREDDKYRL DLLTQAGADV IVLDSSQGNS VYQIAMVHYI KQKYPHLQVI
GGNVVTAAQA KNLIDAGVDG LRVGMGCGSI CITQEVMACG RPQGTAVYKV AEYARRFGVP
VIADGGIQTV GHVVKALALG ASTVMMGSLL AATTEAPGEY FFSDGVRLKK YRGMGSLDAM
EKSSSSQKRY FSEGDKVKIA QGVSGSIQDK GSIQKFVPYL IAGIQHGCQD IGAQSLSVLR
SMMYSGELKF EKRTMSAQIE GGVHGLHSYE KRLY
