ID   IMDH2_RAT               Reviewed;         514 AA.
AC   E9PU28;
DT   22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT   05-APR-2011, sequence version 1.
DT   24-JAN-2024, entry version 76.
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
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   AlphaFoldDB; E9PU28; -.
DR   SMR; E9PU28; -.
DR   STRING; 10116.ENSRNOP00000040635; -.
DR   iPTMnet; E9PU28; -.
DR   PhosphoSitePlus; E9PU28; -.
DR   jPOST; E9PU28; -.
DR   PaxDb; 10116-ENSRNOP00000040635; -.
DR   PeptideAtlas; E9PU28; -.
DR   AGR; RGD:735092; -.
DR   RGD; 735092; Impdh2.
DR   VEuPathDB; HostDB:ENSRNOG00000031965; -.
DR   eggNOG; KOG2550; Eukaryota.
DR   HOGENOM; CLU_022552_2_1_1; -.
DR   InParanoid; E9PU28; -.
DR   PhylomeDB; E9PU28; -.
DR   TreeFam; TF300378; -.
DR   Reactome; R-RNO-6798695; Neutrophil degranulation.
DR   Reactome; R-RNO-73817; Purine ribonucleoside monophosphate biosynthesis.
DR   Reactome; R-RNO-9748787; Azathioprine ADME.
DR   UniPathway; UPA00601; UER00295.
DR   PRO; PR:E9PU28; -.
DR   Proteomes; UP000002494; Chromosome 8.
DR   Bgee; ENSRNOG00000031965; Expressed in spleen and 20 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR   GO; GO:0003938; F:IMP dehydrogenase activity; IDA:RGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0000166; F:nucleotide binding; ISO:RGD.
DR   GO; GO:0097294; P:'de novo' XMP biosynthetic process; ISO:RGD.
DR   GO; GO:0071353; P:cellular response to interleukin-4; ISO:RGD.
DR   GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR   GO; GO:0006177; P:GMP biosynthetic process; ISO:RGD.
DR   GO; GO:0006183; P:GTP biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0046651; P:lymphocyte proliferation; ISO:RGD.
DR   GO; GO:0006164; P:purine nucleotide biosynthetic process; ISO:RGD.
DR   GO; GO:0060041; P:retina development in camera-type eye; IEP:RGD.
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; E9PU28; RN.
PE   1: Evidence at protein level;
KW   Acetylation; CBS domain; Cytoplasm; GMP biosynthesis; Isopeptide bond;
KW   Metal-binding; NAD; Nucleus; Oxidoreductase; Phosphoprotein; Potassium;
KW   Purine biosynthesis; Reference proteome; Repeat; Ubl conjugation.
FT   CHAIN           1..514
FT                   /note="Inosine-5'-monophosphate dehydrogenase 2"
FT                   /id="PRO_0000415674"
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:22673903"
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"
SQ   SEQUENCE   514 AA;  55815 MW;  033F6EED4CF64EA6 CRC64;
     MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD LTSALTKKIT
     LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ ANEVRKVKKY EQGFITDPVV
     LSPKDRVRDV FEAKARHGFC GIPITDTGRM GSRLVGIISS RDIDFLKEEE HDRFLEEIMT
     KREDLVVAPA GVTLKEANEI LQRSKKGKLP IVNESDELVA IIARTDLKKN RDYPLASKDT
     KKQLLCGAAI GTHEDDKYRL DLLALAGVDV VVLDSSQGNS IFQINMIKYI KEKYPNLQVI
     GGNVVTAAQA KNLIDAGVDA LRVGMGSGSI CITQEVLACG RPQATAVYKV SEYARRFGVP
     VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY FFSDGIRLKK YRGMGSLDAM
     DKHLSSQNRY FSEADKIKVA QGVSGAVQDK GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR
     AMMYSGELKF EKRTSSAQVE GGVHGLHSYE KRLF
//