ID U3KN16_RABIT Unreviewed; 598 AA.
AC U3KN16;
DT 13-NOV-2013, integrated into UniProtKB/TrEMBL.
DT 13-NOV-2013, sequence version 1.
DT 27-MAR-2024, entry version 62.
DE RecName: Full=Inosine-5'-monophosphate dehydrogenase {ECO:0000256|HAMAP-Rule:MF_03156, ECO:0000256|RuleBase:RU003928};
DE Short=IMP dehydrogenase {ECO:0000256|HAMAP-Rule:MF_03156};
DE Short=IMPD {ECO:0000256|HAMAP-Rule:MF_03156};
DE Short=IMPDH {ECO:0000256|HAMAP-Rule:MF_03156};
DE EC=1.1.1.205 {ECO:0000256|HAMAP-Rule:MF_03156, ECO:0000256|RuleBase:RU003928};
GN Name=IMPDH1 {ECO:0000313|Ensembl:ENSOCUP00000026625.1};
GN Synonyms=IMPDH {ECO:0000256|HAMAP-Rule:MF_03156};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986 {ECO:0000313|Ensembl:ENSOCUP00000026625.1, ECO:0000313|Proteomes:UP000001811};
RN [1] {ECO:0000313|Ensembl:ENSOCUP00000026625.1, ECO:0000313|Proteomes:UP000001811}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thorbecke inbred {ECO:0000313|Ensembl:ENSOCUP00000026625.1,
RC ECO:0000313|Proteomes:UP000001811};
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2] {ECO:0000313|Ensembl:ENSOCUP00000026625.1}
RP IDENTIFICATION.
RC STRAIN=Thorbecke {ECO:0000313|Ensembl:ENSOCUP00000026625.1};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|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:0000256|HAMAP-Rule:MF_03156,
CC ECO:0000256|RuleBase:RU003928};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000256|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:0000256|HAMAP-Rule:MF_03156}.
CC -!- PATHWAY: Purine metabolism; XMP biosynthesis via de novo pathway; XMP
CC from IMP: step 1/1. {ECO:0000256|HAMAP-Rule:MF_03156,
CC ECO:0000256|RuleBase:RU003928}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000256|HAMAP-Rule:MF_03156}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|HAMAP-Rule:MF_03156}.
CC Nucleus {ECO:0000256|HAMAP-Rule:MF_03156}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000256|HAMAP-
CC Rule:MF_03156, ECO:0000256|RuleBase:RU003927}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_03156}.
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DR EMBL; AAGW02039077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02039078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02039079; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_008256457.1; XM_008258235.2.
DR AlphaFoldDB; U3KN16; -.
DR SMR; U3KN16; -.
DR STRING; 9986.ENSOCUP00000026625; -.
DR PaxDb; 9986-ENSOCUP00000026625; -.
DR Ensembl; ENSOCUT00000033580.2; ENSOCUP00000026625.1; ENSOCUG00000003015.4.
DR eggNOG; KOG2550; Eukaryota.
DR GeneTree; ENSGT00940000154156; -.
DR InParanoid; U3KN16; -.
DR OMA; MGYCGAK; -.
DR OrthoDB; 166969at2759; -.
DR UniPathway; UPA00601; UER00295.
DR Proteomes; UP000001811; Chromosome 7.
DR Bgee; ENSOCUG00000003015; Expressed in brain and 18 other cell types or tissues.
DR ExpressionAtlas; U3KN16; baseline.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:Ensembl.
DR GO; GO:0003938; F:IMP dehydrogenase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006177; P:GMP biosynthetic process; IEA:UniProtKB-UniRule.
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:SF74; INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE 1; 1.
DR PANTHER; PTHR11911; INOSINE-5-MONOPHOSPHATE DEHYDROGENASE RELATED; 1.
DR Pfam; PF00571; CBS; 2.
DR Pfam; PF00478; 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.
PE 3: Inferred from homology;
KW CBS domain {ECO:0000256|ARBA:ARBA00023122, ECO:0000256|PROSITE-
KW ProRule:PRU00703}; Cytoplasm {ECO:0000256|HAMAP-Rule:MF_03156};
KW GMP biosynthesis {ECO:0000256|HAMAP-Rule:MF_03156,
KW ECO:0000256|RuleBase:RU003928};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP-
KW Rule:MF_03156};
KW NAD {ECO:0000256|HAMAP-Rule:MF_03156, ECO:0000256|RuleBase:RU003928};
KW Nucleus {ECO:0000256|HAMAP-Rule:MF_03156};
KW Oxidoreductase {ECO:0000256|HAMAP-Rule:MF_03156,
KW ECO:0000256|RuleBase:RU003927};
KW Potassium {ECO:0000256|ARBA:ARBA00022958, ECO:0000256|HAMAP-Rule:MF_03156};
KW Purine biosynthesis {ECO:0000256|HAMAP-Rule:MF_03156,
KW ECO:0000256|RuleBase:RU003928};
KW Reference proteome {ECO:0000313|Proteomes:UP000001811}.
FT DOMAIN 166..225
FT /note="CBS"
FT /evidence="ECO:0000259|PROSITE:PS51371"
FT DOMAIN 231..289
FT /note="CBS"
FT /evidence="ECO:0000259|PROSITE:PS51371"
FT REGION 1..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 572..598
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 383
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT ACT_SITE 481
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 326..328
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 376..378
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 378
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:0000256|HAMAP-Rule:MF_03156"
FT BINDING 380
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:0000256|HAMAP-Rule:MF_03156"
FT BINDING 381
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 383
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:0000256|HAMAP-Rule:MF_03156"
FT BINDING 416..418
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 439..440
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 463..467
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 493
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 548
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /ligand_note="ligand shared between two tetrameric
FT partners"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
SQ SEQUENCE 598 AA; 63395 MW; 48215DF7F7648287 CRC64;
MEGPLPPPAE PPLQGGGAAA VPEPGARQHP GHETAAQRYS ARLLQAGYEP ESMADYLISG
GTGYVPEDGL TAQQLFASAD GLTYNDFLIL PGFIDFIADE VDLTSALTRK ITLKTPLISS
PMDTVTEADM AIAMALMGGI GFIHHNCTPE FQANEVRKVK KFEQGFITDP VVLSPSHTVG
DVLEAKIRHG FSGIPVTETG AMGSKLVGIV TSRDIDFLAE KDHTTLLSEV MTPRIELVVA
PAGVTLKEAN EILQRSKKGK LPIVNDRDEL VAIIARTDLK KNRDYPLASK DSHKQLLCGA
AVGTREDDKY RLDLLTQAGA DVIVLDSSQG NSVYQIAMVH YIKQKYPHLQ VIGGNVVTAA
QAKNLIDAGV DGLRVGMGCG SICITQEVMA CGRPQGTAVY KVAEYARRFG VPVIADGGIQ
TVGHVVKALA LGASTVMMGS LLAATTEAPG EYFFSDGVRL KKYRGMGSLD AMEKSSSSQK
RYFSEGDKVK IAQGVSGSVQ DKGSIQKFVP YLIAGIQHGC QDIGARSLSV LRSMMYSGEL
KFEKRTMSAQ IEGGVHGLHS YTFLPFTRSG CTEDSGGGRG GGGGVPPGPP SSAASLHG
//
