ID A0A2K6BRG5_MACNE Unreviewed; 634 AA.
AC A0A2K6BRG5;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 27-MAR-2024, entry version 24.
DE RecName: Full=Inosine-5'-monophosphate dehydrogenase {ECO:0000256|HAMAP-Rule:MF_03156};
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};
GN Name=IMPDH {ECO:0000256|HAMAP-Rule:MF_03156};
OS Macaca nemestrina (Pig-tailed macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9545 {ECO:0000313|Ensembl:ENSMNEP00000013985.1, ECO:0000313|Proteomes:UP000233120};
RN [1] {ECO:0000313|Ensembl:ENSMNEP00000013985.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-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 -!- 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 -!- 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}.
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 AlphaFoldDB; A0A2K6BRG5; -.
DR STRING; 9545.ENSMNEP00000013985; -.
DR Ensembl; ENSMNET00000038188.1; ENSMNEP00000013985.1; ENSMNEG00000031193.1.
DR GeneTree; ENSGT00940000154156; -.
DR UniPathway; UPA00601; UER00295.
DR Proteomes; UP000233120; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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; IPR001093; IMP_DH_GMPRt.
DR NCBIfam; TIGR01302; IMP_dehydrog; 1.
DR PANTHER; PTHR11911:SF126; IMP DEHYDROGENASE; 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.
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 Metal-binding {ECO:0000256|HAMAP-Rule:MF_03156};
KW NAD {ECO:0000256|HAMAP-Rule:MF_03156};
KW Nucleus {ECO:0000256|HAMAP-Rule:MF_03156};
KW Oxidoreductase {ECO:0000256|HAMAP-Rule:MF_03156};
KW Potassium {ECO:0000256|HAMAP-Rule:MF_03156};
KW Purine biosynthesis {ECO:0000256|HAMAP-Rule:MF_03156};
KW Reference proteome {ECO:0000313|Proteomes:UP000233120}.
FT DOMAIN 213..272
FT /note="CBS"
FT /evidence="ECO:0000259|PROSITE:PS51371"
FT DOMAIN 278..336
FT /note="CBS"
FT /evidence="ECO:0000259|PROSITE:PS51371"
FT REGION 604..634
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 430
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT ACT_SITE 527
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 373..375
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 423..425
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 425
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 427
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 428
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 430
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 463..465
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 486..487
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 509..513
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 539
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03156"
FT BINDING 594
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 634 AA; 68123 MW; 962972CD8183AF75 CRC64;
MPVAPRLPQP PRKLGLTAPA NHAQLIFFVF QIRRVSPWFA RMYSISLTFV IGPLRSPKCW
ITGREPPTPR PILLILKTFG RARGSRLVIP ALVAGCSGSM ADYLISGGTL YVPEDGLTAQ
QLFASADGLT YDDFLILPGF IDFLTGEVDL TSALTRKITL KTPLISFPTD TVTEADMAIA
MALMGGIGFI HHNCTPEFQA NKVQKVKKFE QGFITDPVVL SPSHTVGDVL EAKVRHGFSG
IPITETGTMG SKLVGIVTSR DIDFLAEKDH TTLLSEVMTP RIELVVAPAG VTFEEANEIL
KRSKKGKLPI VNDHDELVAI IARTNLKKNR DYPLASKDSH KQLLCGAVVG TREDDKFRLD
LLTQAGVDVI VLDSSQGNLV YQIAMVHYTK QKYPHLQVIG GNVVTAAQAK NLIDAGVDGL
HVGMGCGSIC ITPEVMACGR IHGSAVYKVA EYARRFGVPI IADGGIQTLG HVVKALALGA
STVMMGSLLA ATTEASAEYF SDGVPLKKYQ GMGSLDAMEK SSSSQKRYFS EGDKVKFAQS
ISGSIQDKGF IQKFVPYLIA GIQHSCQDIG ARSLSVLRSM MYSGELKFEK RTVSAQMEGG
VHGLSGCTED SGGGQDGGRG VPRCPPSGAA SRHN
//
