IMDH2_HUMAN
ID IMDH2_HUMAN Reviewed; 514 AA.
AC P12268; Q6LEF3;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 2.
DT 03-AUG-2022, entry version 242.
DE RecName: Full=Inosine-5'-monophosphate dehydrogenase 2 {ECO:0000303|PubMed:24477477};
DE Short=IMP dehydrogenase 2;
DE Short=IMPD 2;
DE Short=IMPDH 2;
DE EC=1.1.1.205 {ECO:0000269|PubMed:7763314, ECO:0000269|PubMed:7903306};
DE AltName: Full=Inosine-5'-monophosphate dehydrogenase type II {ECO:0000303|PubMed:7896827};
DE Short=IMP dehydrogenase II;
DE Short=IMPDH-II;
GN Name=IMPDH2 {ECO:0000312|HGNC:HGNC:6053}; Synonyms=IMPD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2902093; DOI=10.1016/s0021-9258(19)37654-9;
RA Collart F.R., Huberman E.;
RT "Cloning and sequence analysis of the human and Chinese hamster inosine-5'-
RT monophosphate dehydrogenase cDNAs.";
RL J. Biol. Chem. 263:15769-15772(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RX PubMed=1969416; DOI=10.1016/s0021-9258(19)34120-1;
RA Natsumeda Y., Ohno S., Kawasaki H., Konno Y., Weber G., Suzuki K.;
RT "Two distinct cDNAs for human IMP dehydrogenase.";
RL J. Biol. Chem. 265:5292-5295(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Blood;
RX PubMed=7999076; DOI=10.1006/bbrc.1994.2698;
RA Glesne D.A., Huberman E.;
RT "Cloning and sequence of the human type II IMP dehydrogenase gene.";
RL Biochem. Biophys. Res. Commun. 205:537-544(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7896827; DOI=10.1074/jbc.270.12.6808;
RA Zimmermann A.G., Spychala J., Mitchell B.S.;
RT "Characterization of the human inosine-5'-monophosphate dehydrogenase type
RT II gene.";
RL J. Biol. Chem. 270:6808-6814(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=B-cell, Colon, and Placenta;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 461-514.
RX PubMed=8098009; DOI=10.1006/geno.1993.1177;
RA Glesne D.A., Collart F.R., Varkony T., Drabkin H., Huberman E.;
RT "Chromosomal localization and structure of the human type II IMP
RT dehydrogenase gene.";
RL Genomics 16:274-277(1993).
RN [7]
RP PROTEIN SEQUENCE OF 2-11, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, ACTIVITY
RP REGULATION, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=7903306; DOI=10.1016/s0021-9258(19)74247-1;
RA Carr S.F., Papp E., Wu J.C., Natsumeda Y.;
RT "Characterization of human type I and type II IMP dehydrogenases.";
RL J. Biol. Chem. 268:27286-27290(1993).
RN [8]
RP PROTEIN SEQUENCE OF N-TERMINUS, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION,
RP AND CATALYTIC ACTIVITY.
RX PubMed=7763314; DOI=10.1016/0006-2952(95)00026-v;
RA Hager P.W., Collart F.R., Huberman E., Mitchell B.S.;
RT "Recombinant human inosine monophosphate dehydrogenase type I and type II
RT proteins. Purification and characterization of inhibitor binding.";
RL Biochem. Pharmacol. 49:1323-1329(1995).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [10]
RP SUBCELLULAR LOCATION, NUCLEIC ACID-BINDING, AND FUNCTION.
RX PubMed=14766016; DOI=10.1042/bj20031585;
RA McLean J.E., Hamaguchi N., Belenky P., Mortimer S.E., Stanton M.,
RA Hedstrom L.;
RT "Inosine 5'-monophosphate dehydrogenase binds nucleic acids in vitro and in
RT vivo.";
RL Biochem. J. 379:243-251(2004).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-400, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [13]
RP POLYMORPHISM, AND VARIANT PHE-263.
RX PubMed=17496727; DOI=10.1097/fpc.0b013e328012b8cf;
RA Wang J., Zeevi A., Webber S., Girnita D.M., Addonizio L., Selby R.,
RA Hutchinson I.V., Burckart G.J.;
RT "A novel variant L263F in human inosine 5'-monophosphate dehydrogenase 2 is
RT associated with diminished enzyme activity.";
RL Pharmacogenet. Genomics 17:283-290(2007).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-511, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122 AND SER-416, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-122; SER-160 AND SER-416, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [22]
RP ACETYLATION, AND INTERACTION WITH CLOCK.
RX PubMed=28985504; DOI=10.1016/j.molcel.2017.09.008;
RA Lin R., Mo Y., Zha H., Qu Z., Xie P., Zhu Z.J., Xu Y., Xiong Y., Guan K.L.;
RT "CLOCK acetylates ASS1 to drive circadian rhythm of ureagenesis.";
RL Mol. Cell 68:198-209(2017).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=24477477; DOI=10.1007/s00018-014-1567-6;
RA Calise S.J., Carcamo W.C., Krueger C., Yin J.D., Purich D.L., Chan E.K.;
RT "Glutamine deprivation initiates reversible assembly of mammalian rods and
RT rings.";
RL Cell. Mol. Life Sci. 71:2963-2973(2014).
RN [24]
RP UBIQUITINATION, AND INTERACTION WITH ANKRD9.
RX PubMed=30293565; DOI=10.1016/j.bbadis.2018.07.001;
RA Lee Y., Lim B., Lee S.W., Lee W.R., Kim Y.I., Kim M., Ju H., Kim M.Y.,
RA Kang S.J., Song J.J., Lee J.E., Kang C.;
RT "ANKRD9 is associated with tumor suppression as a substrate receptor
RT subunit of ubiquitin ligase.";
RL Biochim. Biophys. Acta 1864:3145-3153(2018).
RN [25]
RP SUBCELLULAR LOCATION.
RX PubMed=31337707; DOI=10.1074/jbc.ra119.008231;
RA Hayward D., Kouznetsova V.L., Pierson H.E., Hasan N.M., Guzman E.R.,
RA Tsigelny I.F., Lutsenko S.;
RT "ANKRD9 is a metabolically-controlled regulator of IMPDH2 abundance and
RT macro-assembly.";
RL J. Biol. Chem. 294:14454-14466(2019).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-195; LYS-208 AND LYS-438, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS), AND ACTIVE SITE.
RX PubMed=10097070; DOI=10.1073/pnas.96.7.3531;
RA Colby T.D., Vanderveen K., Strickler M.D., Markham G.D., Goldstein B.M.;
RT "Crystal structure of human type II inosine monophosphate dehydrogenase:
RT implications for ligand binding and drug design.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3531-3536(1999).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) IN COMPLEX WITH INHIBITOR AND
RP POTASSIUM.
RA Risal D., Strickler M.D., Goldstein B.M.;
RT "Crystal structure of human inosine monophosphate dehydrogenase type II
RT complexed with the MPA/NAD analog C2-MAD.";
RL Submitted (DEC-2002) to the PDB data bank.
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) IN COMPLEX WITH NAD(+).
RA Risal D., Strickler M.D., Goldstein B.M.;
RT "The conformation of NAD bound to human inosine monophosphate Dehydrogenase
RT Type II.";
RL Submitted (DEC-2002) to the PDB data bank.
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 (PubMed:7903306, PubMed:7763314). Could also have a single-stranded
CC nucleic acid-binding activity and could play a role in RNA and/or DNA
CC metabolism (PubMed:14766016). It may also have a role in the
CC development of malignancy and the growth progression of some tumors.
CC {ECO:0000269|PubMed:14766016, ECO:0000269|PubMed:7763314,
CC ECO:0000269|PubMed:7903306}.
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:0000269|PubMed:7763314,
CC ECO:0000269|PubMed:7903306};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
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. Subject to product inhibition by XMP and NADH
CC (PubMed:7903306). Also inhibited by ADP. {ECO:0000255|HAMAP-
CC Rule:MF_03156, ECO:0000269|PubMed:7903306}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.3 uM for Inosine 5'-phosphate {ECO:0000269|PubMed:7763314,
CC ECO:0000269|PubMed:7903306};
CC KM=32 uM for NAD(+) {ECO:0000269|PubMed:7763314,
CC ECO:0000269|PubMed:7903306};
CC -!- PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP
CC from IMP: step 1/1. {ECO:0000269|PubMed:7763314,
CC ECO:0000269|PubMed:7903306}.
CC -!- SUBUNIT: Homotetramer (PubMed:7903306, Ref.28, Ref.29). Interacts with
CC CLOCK; in a circadian manner (PubMed:28985504). Interacts with ANKRD9;
CC leading to its ubiquitination and degradation by the proteasome
CC (PubMed:30293565). {ECO:0000269|PubMed:28985504,
CC ECO:0000269|PubMed:30293565, ECO:0000269|PubMed:7903306,
CC ECO:0000269|Ref.28, ECO:0000269|Ref.29}.
CC -!- INTERACTION:
CC P12268; O95994: AGR2; NbExp=3; IntAct=EBI-353389, EBI-712648;
CC P12268; Q96GX9: APIP; NbExp=3; IntAct=EBI-353389, EBI-359248;
CC P12268; Q9BU20: CPLANE2; NbExp=6; IntAct=EBI-353389, EBI-750332;
CC P12268; Q8WWZ1: IL1F10; NbExp=3; IntAct=EBI-353389, EBI-13318821;
CC P12268; P20839-3: IMPDH1; NbExp=3; IntAct=EBI-353389, EBI-12188657;
CC P12268; P78424: POU6F2; NbExp=3; IntAct=EBI-353389, EBI-12029004;
CC P12268; P40763: STAT3; NbExp=3; IntAct=EBI-353389, EBI-518675;
CC P12268; Q12933: TRAF2; NbExp=3; IntAct=EBI-353389, EBI-355744;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14766016}. Nucleus
CC {ECO:0000269|PubMed:14766016}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:31337707}. Note=Can form fiber-like subcellular
CC structures termed 'cytoophidia' in response to intracellular guanine-
CC nucleotide depletion. {ECO:0000269|PubMed:24477477,
CC ECO:0000269|PubMed:31337707}.
CC -!- TISSUE SPECIFICITY: IMPDH1 is the main species in normal leukocytes and
CC IMPDH2 predominates over IMPDH1 in the tumor.
CC -!- INDUCTION: Selectively up-regulated in neoplastic and replicating
CC cells.
CC -!- PTM: Ubiquitinated leading to its degradation by the proteasome.
CC {ECO:0000269|PubMed:30293565}.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Acetylated by CLOCK in a circadian manner (PubMed:28985504).
CC {ECO:0000269|PubMed:28985504}.
CC -!- POLYMORPHISM: Genetic variants in the IMPDH2 gene are responsible for
CC the large inter-individual variability in enzyme activity and may
CC influence immunosuppressive efficacy and side effects in transplant
CC recipients receiving mycophenolic acid [MIM:617995].
CC {ECO:0000269|PubMed:17496727}.
CC -!- MISCELLANEOUS: Because IMPDH activity is tightly linked with cell
CC proliferation, it has been recognized as a target for cancer and viral
CC chemotherapy and as a target for immunosuppressive drugs. The
CC activities of the antitumor drug tiazofurin, the antiviral drug
CC ribavirin, and the immunosuppressive drugs mizoribine and mycophenolic
CC acid (MPA) are attributed to the inhibition of IMPDH. In addition,
CC bacterial and parasitic IMPDH's differ significantly from mammalian
CC enzymes, which makes it a suitable target for anti-infective drugs.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC Rule:MF_03156}.
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DR EMBL; J04208; AAA36112.1; -; mRNA.
DR EMBL; L33842; AAA67054.1; -; Genomic_DNA.
DR EMBL; L39210; AAB70699.1; -; Genomic_DNA.
DR EMBL; BC006124; AAH06124.1; -; mRNA.
DR EMBL; BC012840; AAH12840.1; -; mRNA.
DR EMBL; BC015567; AAH15567.1; -; mRNA.
DR EMBL; L08114; AAA36113.1; -; Genomic_DNA.
DR CCDS; CCDS2786.1; -.
DR PIR; I52303; A31997.
DR RefSeq; NP_000875.2; NM_000884.2.
DR PDB; 1B3O; X-ray; 2.90 A; A/B=1-514.
DR PDB; 1NF7; X-ray; 2.65 A; A/B=1-514.
DR PDB; 1NFB; X-ray; 2.90 A; A/B=1-514.
DR PDB; 6I0M; X-ray; 2.57 A; A/B=1-514.
DR PDB; 6I0O; X-ray; 2.62 A; A/B=1-514.
DR PDB; 6U8E; EM; 3.03 A; A/B/C/D/E/F/G/H=1-514.
DR PDB; 6U8N; EM; 3.29 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-514.
DR PDB; 6U8R; EM; 3.91 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-514.
DR PDB; 6U8S; EM; 3.14 A; A/B/C/D/E/F/G/H=1-514.
DR PDB; 6U9O; EM; 3.36 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-514.
DR PDB; 6UA2; EM; 4.20 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-514.
DR PDB; 6UA4; EM; 3.65 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-514.
DR PDB; 6UA5; EM; 3.79 A; A/B/C/D/E/F/G/H=1-514.
DR PDB; 6UAJ; EM; 3.84 A; A/B/C/D/E/F/G/H=1-514.
DR PDB; 6UC2; EM; 4.48 A; A/B/C/D/E/F/G/H=1-514.
DR PDB; 6UDO; EM; 3.21 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-514.
DR PDB; 6UDP; EM; 2.95 A; A/B/C/D/E/F/G/H=1-514.
DR PDB; 6UDQ; EM; 3.27 A; A/B/C/D/E/F/G/H/I/J/K/L=1-514.
DR PDBsum; 1B3O; -.
DR PDBsum; 1NF7; -.
DR PDBsum; 1NFB; -.
DR PDBsum; 6I0M; -.
DR PDBsum; 6I0O; -.
DR PDBsum; 6U8E; -.
DR PDBsum; 6U8N; -.
DR PDBsum; 6U8R; -.
DR PDBsum; 6U8S; -.
DR PDBsum; 6U9O; -.
DR PDBsum; 6UA2; -.
DR PDBsum; 6UA4; -.
DR PDBsum; 6UA5; -.
DR PDBsum; 6UAJ; -.
DR PDBsum; 6UC2; -.
DR PDBsum; 6UDO; -.
DR PDBsum; 6UDP; -.
DR PDBsum; 6UDQ; -.
DR AlphaFoldDB; P12268; -.
DR SMR; P12268; -.
DR BioGRID; 109828; 299.
DR IntAct; P12268; 86.
DR MINT; P12268; -.
DR STRING; 9606.ENSP00000321584; -.
DR BindingDB; P12268; -.
DR ChEMBL; CHEMBL2002; -.
DR DrugBank; DB03948; 6-Chloropurine Riboside, 5'-Monophosphate.
DR DrugBank; DB00993; Azathioprine.
DR DrugBank; DB04566; Inosinic Acid.
DR DrugBank; DB01033; Mercaptopurine.
DR DrugBank; DB00688; Mycophenolate mofetil.
DR DrugBank; DB01024; Mycophenolic acid.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00811; Ribavirin.
DR DrugBank; DB03070; Selenazole-4-carboxyamide-adenine dinucleotide.
DR DrugBank; DB06103; VX-148.
DR DrugCentral; P12268; -.
DR GuidetoPHARMACOLOGY; 2625; -.
DR GlyGen; P12268; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P12268; -.
DR MetOSite; P12268; -.
DR PhosphoSitePlus; P12268; -.
DR SwissPalm; P12268; -.
DR BioMuta; IMPDH2; -.
DR DMDM; 124419; -.
DR REPRODUCTION-2DPAGE; IPI00291510; -.
DR REPRODUCTION-2DPAGE; P12268; -.
DR UCD-2DPAGE; P12268; -.
DR EPD; P12268; -.
DR jPOST; P12268; -.
DR MassIVE; P12268; -.
DR MaxQB; P12268; -.
DR PaxDb; P12268; -.
DR PeptideAtlas; P12268; -.
DR PRIDE; P12268; -.
DR ProteomicsDB; 52839; -.
DR TopDownProteomics; P12268; -.
DR Antibodypedia; 30367; 399 antibodies from 38 providers.
DR DNASU; 3615; -.
DR Ensembl; ENST00000326739.9; ENSP00000321584.4; ENSG00000178035.13.
DR GeneID; 3615; -.
DR KEGG; hsa:3615; -.
DR MANE-Select; ENST00000326739.9; ENSP00000321584.4; NM_000884.3; NP_000875.2.
DR UCSC; uc003cvt.4; human.
DR CTD; 3615; -.
DR DisGeNET; 3615; -.
DR GeneCards; IMPDH2; -.
DR HGNC; HGNC:6053; IMPDH2.
DR HPA; ENSG00000178035; Low tissue specificity.
DR MalaCards; IMPDH2; -.
DR MIM; 146691; gene.
DR MIM; 617995; phenotype.
DR neXtProt; NX_P12268; -.
DR OpenTargets; ENSG00000178035; -.
DR PharmGKB; PA29863; -.
DR VEuPathDB; HostDB:ENSG00000178035; -.
DR eggNOG; KOG2550; Eukaryota.
DR GeneTree; ENSGT00940000157726; -.
DR OrthoDB; 618077at2759; -.
DR PhylomeDB; P12268; -.
DR TreeFam; TF300378; -.
DR BioCyc; MetaCyc:HS11242-MON; -.
DR BRENDA; 1.1.1.205; 2681.
DR PathwayCommons; P12268; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-73817; Purine ribonucleoside monophosphate biosynthesis.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR Reactome; R-HSA-9748787; Azathioprine ADME.
DR SABIO-RK; P12268; -.
DR SignaLink; P12268; -.
DR SIGNOR; P12268; -.
DR UniPathway; UPA00601; UER00295.
DR BioGRID-ORCS; 3615; 364 hits in 1105 CRISPR screens.
DR ChiTaRS; IMPDH2; human.
DR EvolutionaryTrace; P12268; -.
DR GeneWiki; IMPDH2; -.
DR GenomeRNAi; 3615; -.
DR Pharos; P12268; Tclin.
DR PRO; PR:P12268; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P12268; protein.
DR Bgee; ENSG00000178035; Expressed in left ovary and 211 other tissues.
DR ExpressionAtlas; P12268; baseline and differential.
DR Genevisible; P12268; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005778; C:peroxisomal membrane; HDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0003938; F:IMP dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000166; F:nucleotide binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0097294; P:'de novo' XMP biosynthetic process; IEA:Ensembl.
DR GO; GO:0071353; P:cellular response to interleukin-4; IEA:Ensembl.
DR GO; GO:0007623; P:circadian rhythm; IDA:UniProtKB.
DR GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-UniRule.
DR GO; GO:0006183; P:GTP biosynthetic process; IDA:UniProtKB.
DR GO; GO:0046651; P:lymphocyte proliferation; IEA:Ensembl.
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 3D-structure; Acetylation; CBS domain; Cytoplasm;
KW Direct protein sequencing; DNA-binding; GMP biosynthesis; Isopeptide bond;
KW Metal-binding; NAD; Nucleus; Oxidoreductase; Phosphoprotein; Potassium;
KW Purine biosynthesis; Reference proteome; Repeat; RNA-binding;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156,
FT ECO:0000269|PubMed:7903306"
FT CHAIN 2..514
FT /note="Inosine-5'-monophosphate dehydrogenase 2"
FT /id="PRO_0000093673"
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 ECO:0000269|PubMed:10097070"
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 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 ECO:0000269|Ref.28"
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 ECO:0000269|Ref.28"
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 ECO:0000269|Ref.28"
FT BINDING 364..366
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT BINDING 387..388
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
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:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 160
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 400
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 511
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT CROSSLNK 195
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 208
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 438
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 263
FT /note="L -> F (results in 10-fold decrease of enzymatic
FT activity; dbSNP:rs121434586)"
FT /evidence="ECO:0000269|PubMed:17496727"
FT /id="VAR_070542"
FT CONFLICT 190..191
FT /note="AG -> RS (in Ref. 1; AAA36112)"
FT /evidence="ECO:0000305"
FT HELIX 2..5
FT /evidence="ECO:0007829|PDB:6UDP"
FT TURN 6..9
FT /evidence="ECO:0007829|PDB:6UDP"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:1B3O"
FT HELIX 20..24
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 53..58
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 65..67
FT /evidence="ECO:0007829|PDB:6I0M"
FT TURN 71..73
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 76..85
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:6U8E"
FT HELIX 97..110
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 113..117
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:1B3O"
FT HELIX 127..136
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 148..158
FT /evidence="ECO:0007829|PDB:6I0M"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 167..170
FT /evidence="ECO:0007829|PDB:6I0O"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:6I0M"
FT TURN 182..184
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:6UDQ"
FT HELIX 194..204
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 206..212
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:1NF7"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 224..232
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:6I0O"
FT HELIX 256..265
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 270..273
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 281..293
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 297..304
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 307..315
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 319..323
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 328..331
FT /evidence="ECO:0007829|PDB:1NF7"
FT HELIX 334..337
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 343..354
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 355..357
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 361..365
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 370..378
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 382..387
FT /evidence="ECO:0007829|PDB:6I0M"
FT TURN 388..392
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 396..398
FT /evidence="ECO:0007829|PDB:1NF7"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:6U8E"
FT STRAND 404..406
FT /evidence="ECO:0007829|PDB:1NF7"
FT STRAND 409..412
FT /evidence="ECO:0007829|PDB:1NF7"
FT TURN 417..419
FT /evidence="ECO:0007829|PDB:1NF7"
FT STRAND 444..447
FT /evidence="ECO:0007829|PDB:1NF7"
FT HELIX 453..471
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 476..484
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 490..492
FT /evidence="ECO:0007829|PDB:6I0M"
FT HELIX 495..500
FT /evidence="ECO:0007829|PDB:6I0M"
FT STRAND 507..510
FT /evidence="ECO:0007829|PDB:6UDP"
SQ SEQUENCE 514 AA; 55805 MW; 876BEA0EC1DDBEE9 CRC64;
MADYLISGGT SYVPDDGLTA QQLFNCGDGL TYNDFLILPG YIDFTADQVD LTSALTKKIT
LKTPLVSSPM DTVTEAGMAI AMALTGGIGF IHHNCTPEFQ ANEVRKVKKY EQGFITDPVV
LSPKDRVRDV FEAKARHGFC GIPITDTGRM GSRLVGIISS RDIDFLKEEE HDCFLEEIMT
KREDLVVAPA GITLKEANEI LQRSKKGKLP IVNEDDELVA IIARTDLKKN RDYPLASKDA
KKQLLCGAAI GTHEDDKYRL DLLAQAGVDV VVLDSSQGNS IFQINMIKYI KDKYPNLQVI
GGNVVTAAQA KNLIDAGVDA LRVGMGSGSI CITQEVLACG RPQATAVYKV SEYARRFGVP
VIADGGIQNV GHIAKALALG ASTVMMGSLL AATTEAPGEY FFSDGIRLKK YRGMGSLDAM
DKHLSSQNRY FSEADKIKVA QGVSGAVQDK GSIHKFVPYL IAGIQHSCQD IGAKSLTQVR
AMMYSGELKF EKRTSSAQVE GGVHSLHSYE KRLF
