IMDH_DROME
ID IMDH_DROME Reviewed; 537 AA.
AC Q07152; Q26455; Q8SXM5; Q9W2R8;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Inosine-5'-monophosphate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMP dehydrogenase {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMPD {ECO:0000255|HAMAP-Rule:MF_03156};
DE Short=IMPDH {ECO:0000255|HAMAP-Rule:MF_03156};
DE EC=1.1.1.205 {ECO:0000255|HAMAP-Rule:MF_03156};
DE AltName: Full=Protein raspberry;
GN Name=ras; ORFNames=CG1799;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Oregon-R; TISSUE=Embryo;
RA Nash D., Hu S.;
RT "Drosophila inosine monophosphate dehydrogenase is encoded at the raspberry
RT locus.";
RL (In) Proceedings of the 35th meeting of the Canadian Federation of
RL Biological Societies, pp.72-72, Victoria (1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=Oregon-R; TISSUE=Embryo;
RX PubMed=7911114; DOI=10.1139/g94-046;
RA Nash D., Hu S., Leonard N.J., Tiong S.Y., Fillips D.;
RT "The raspberry locus of Drosophila melanogaster includes an inosine
RT monophosphate dehydrogenase like coding sequence.";
RL Genome 37:333-344(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Canton-S;
RX PubMed=7904480;
RA Sifri C.D., Wilson K., Smolik S., Forte M.A., Ullman B.;
RT "Cloning and sequence analysis of a Drosophila melanogaster cDNA encoding
RT IMP dehydrogenase.";
RL Biochim. Biophys. Acta 1217:103-106(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=7476879; DOI=10.1007/bf02191716;
RA Slee R., Bownes M.;
RT "The raspberry locus encodes Drosophila inosine monophosphate
RT dehydrogenase.";
RL Mol. Gen. Genet. 248:755-766(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [6]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
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:0000255|HAMAP-Rule:MF_03156, ECO:0000269|PubMed:7476879,
CC ECO:0000269|PubMed:7911114}.
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. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- TISSUE SPECIFICITY: Enriched in adult ovary and testis.
CC {ECO:0000269|PubMed:7476879}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC {ECO:0000269|PubMed:7476879}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC Rule:MF_03156}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL90291.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L14847; AAA21831.1; -; Genomic_DNA.
DR EMBL; L22608; AAA16839.1; -; mRNA.
DR EMBL; S80430; AAB35628.1; -; mRNA.
DR EMBL; AE014298; AAF46621.3; -; Genomic_DNA.
DR EMBL; AE014298; AAF46622.1; -; Genomic_DNA.
DR EMBL; AY089553; AAL90291.1; ALT_FRAME; mRNA.
DR PIR; S41064; S41064.
DR PIR; S59508; S59508.
DR RefSeq; NP_001259427.1; NM_001272498.2.
DR RefSeq; NP_524646.5; NM_079907.7.
DR RefSeq; NP_727441.1; NM_167240.3.
DR RefSeq; NP_727442.1; NM_167241.3.
DR AlphaFoldDB; Q07152; -.
DR SMR; Q07152; -.
DR BioGRID; 68684; 12.
DR DIP; DIP-21552N; -.
DR IntAct; Q07152; 4.
DR STRING; 7227.FBpp0304573; -.
DR iPTMnet; Q07152; -.
DR PaxDb; Q07152; -.
DR PRIDE; Q07152; -.
DR DNASU; 43873; -.
DR EnsemblMetazoa; FBtr0071494; FBpp0071423; FBgn0003204.
DR EnsemblMetazoa; FBtr0071495; FBpp0071424; FBgn0003204.
DR EnsemblMetazoa; FBtr0332294; FBpp0304573; FBgn0003204.
DR EnsemblMetazoa; FBtr0343043; FBpp0309791; FBgn0003204.
DR GeneID; 43873; -.
DR KEGG; dme:Dmel_CG1799; -.
DR CTD; 19412; -.
DR FlyBase; FBgn0003204; ras.
DR VEuPathDB; VectorBase:FBgn0003204; -.
DR eggNOG; KOG2550; Eukaryota.
DR GeneTree; ENSGT00940000154156; -.
DR HOGENOM; CLU_022552_2_1_1; -.
DR InParanoid; Q07152; -.
DR OMA; MGYCGAK; -.
DR OrthoDB; 618077at2759; -.
DR PhylomeDB; Q07152; -.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR Reactome; R-DME-73817; Purine ribonucleoside monophosphate biosynthesis.
DR Reactome; R-DME-9748787; Azathioprine ADME.
DR UniPathway; UPA00601; UER00295.
DR BioGRID-ORCS; 43873; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 43873; -.
DR PRO; PR:Q07152; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0003204; Expressed in eye disc (Drosophila) and 40 other tissues.
DR ExpressionAtlas; Q07152; baseline and differential.
DR Genevisible; Q07152; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0003938; F:IMP dehydrogenase activity; ISS:FlyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0007411; P:axon guidance; IMP:FlyBase.
DR GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006183; P:GTP biosynthetic process; IBA:GO_Central.
DR GO; GO:0006164; P:purine nucleotide biosynthetic process; ISS:FlyBase.
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; IPR046342; CBS_dom_sf.
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 SUPFAM; SSF54631; SSF54631; 1.
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; NAD;
KW Oxidoreductase; Phosphoprotein; Potassium; Purine biosynthesis;
KW Reference proteome; Repeat.
FT CHAIN 1..537
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000093678"
FT DOMAIN 136..195
FT /note="CBS 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT DOMAIN 200..256
FT /note="CBS 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 350
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 293..295
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 343..345
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 345
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 347
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 348
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 350
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 383..385
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 406..407
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 430..434
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 464
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 523
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 524
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 28
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 38
FT /note="D -> V (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 53
FT /note="T -> P (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 99..102
FT /note="EMAI -> RCH (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 184
FT /note="D -> A (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="V -> S (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 216..217
FT /note="AN -> EH (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 226..229
FT /note="GKLP -> ATA (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="T -> A (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 261..262
FT /note="KQ -> TR (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 265..266
FT /note="VG -> CP (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 277..278
FT /note="AR -> GCRA (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="A -> R (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="Y -> I (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
FT CONFLICT 387..388
FT /note="QS -> HA (in Ref. 4; AAB35628)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 537 AA; 57829 MW; A5EAB41AEAA64EBD CRC64;
MESTTKVKVN GFVESTSSSA APAIQTKSTT GFDAELQDGL SCKELFQNGE GLTYNDFLIL
PGYIDFTAEE VDLSSPLTKS LTLRAPLVSS PMDTVTESEM AIAMALCGGI GIIHHNCTPE
YQALEVHKVK KYKHGFMRDP SVMSPTNTVG DVLEARRKNG FTGYPVTENG KLGGKLLGMV
TSRDIDFREN QPEVLLADIM TTELVTAPNG INLPTANAIL EKSKKGKLPI VNQAGELVAM
IARTDLKKAR SYPNASKDSN KQLLVGAAIG TRSEDKARLA LLVANGVDVI ILDSSQGNSV
YQVEMIKYIK ETYPELQVIG GNVVTRAQAK NLIDAGVDGL RVGMGSGSIC ITQEVMACGC
PQATAVYQVS TYARQFGVPV IADGGIQSIG HIVKAIALGA SAVMMGSLLA GTSEAPGEYF
FSDGVRLKKY RGMGSLEAME RGDAKGAAMS RYYHNEMDKM KVAQGVSGSI VDKGSVLRYL
PYLECGLQHS CQDIGANSIN KLRDMIYNGQ LRFMKRTHSA QLEGNVHGLF SYEKRLF
