MPAF_PENRF
ID MPAF_PENRF Reviewed; 526 AA.
AC W6QIT2;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
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=Mycophenolic acid biosynthesis cluster protein F {ECO:0000303|PubMed:26751579};
GN Name=mpaF {ECO:0000303|PubMed:26751579}; Synonyms=IMH3;
GN ORFNames=PROQFM164_S05g000556 {ECO:0000312|EMBL:CDM36723.1};
OS Penicillium roqueforti (strain FM164).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=1365484;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FM164;
RX PubMed=24407037; DOI=10.1038/ncomms3876;
RA Cheeseman K., Ropars J., Renault P., Dupont J., Gouzy J., Branca A.,
RA Abraham A.L., Ceppi M., Conseiller E., Debuchy R., Malagnac F., Goarin A.,
RA Silar P., Lacoste S., Sallet E., Bensimon A., Giraud T., Brygoo Y.;
RT "Multiple recent horizontal transfers of a large genomic region in cheese
RT making fungi.";
RL Nat. Commun. 5:2876-2876(2014).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=26751579; DOI=10.1371/journal.pone.0147047;
RA Del-Cid A., Gil-Duran C., Vaca I., Rojas-Aedo J.F., Garcia-Rico R.O.,
RA Levican G., Chavez R.;
RT "Identification and functional analysis of the mycophenolic acid gene
RT cluster of Penicillium roqueforti.";
RL PLoS ONE 11:E0147047-E0147047(2016).
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 (By
CC similarity). Part of the gene cluster that mediates the biosynthesis of
CC mycophenolic acid (MPA), the first isolated antibiotic natural product
CC in the world (PubMed:26751579). Does not play a role in the
CC biosynthesis of MPA, but is involved in self resistance to MPA, since
CC MPA acts as an inhibitor of IMP dehydrogenases (PubMed:26751579).
CC {ECO:0000255|HAMAP-Rule:MF_03156, ECO:0000269|PubMed:26751579}.
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: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:26751579}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03156}.
CC -!- DISRUPTION PHENOTYPE: Increases the sensitivity of P.roqueforti towards
CC MPA and decreases MPA production by the fungus.
CC {ECO:0000269|PubMed:26751579}.
CC -!- SIMILARITY: Belongs to the IMPDH/GMPR family. {ECO:0000255|HAMAP-
CC Rule:MF_03156}.
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DR EMBL; HG792019; CDM36723.1; -; Genomic_DNA.
DR AlphaFoldDB; W6QIT2; -.
DR SMR; W6QIT2; -.
DR STRING; 1365484.W6QIT2; -.
DR EnsemblFungi; CDM36723; CDM36723; PROQFM164_S05g000556.
DR OrthoDB; 618077at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000030686; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; 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 GO; GO:0140729; P:self-resistance to endogenously produced metabolite; ISS:GO_Central.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
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 3: Inferred from homology;
KW CBS domain; Cytoplasm; GMP biosynthesis; Metal-binding; NAD;
KW Oxidoreductase; Potassium; Purine biosynthesis.
FT CHAIN 1..526
FT /note="Inosine-5'-monophosphate dehydrogenase"
FT /id="PRO_0000449217"
FT DOMAIN 120..179
FT /note="CBS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT DOMAIN 183..239
FT /note="CBS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT REGION 506..526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 333
FT /note="Thioimidate intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT ACT_SITE 439
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 276..278
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 326..328
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
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 330
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 331
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 333
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 366..368
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 389..390
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 451
FT /ligand="IMP"
FT /ligand_id="ChEBI:CHEBI:58053"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03156"
FT BINDING 506
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"
SQ SEQUENCE 526 AA; 55877 MW; 6C9149C77AE5F77C CRC64;
MVEILDYTKA LEVLKEYPGD GLHVDTLLDS DSHGALTYND FLILPGSITF PASDVSLETR
VTRRFTIKAP LLSSPMDTVT EHSMAIHMAL LGGLGVIHNN CPPDEQAEMV RKVKRYENGF
IQDPIVLSPE TTVGEAKELK TKWGFGGFPV TEKGTLHSKL LGIVTSRDIQ FHKNHEDPVT
AVMATDLVTA PAGTTLAEAN EVLRSSKKGK LPIVDKDGSL ISLLSRSDLM KNIHYPLASK
LPSKQLLCAA AISTHDADKV RLQKLVDAGL DIVVVDSSQG HSTFQIAMIK YIKQNFPDID
VIGGNIVTRE QAAALIAAGA DGLRIGMGSG SACITQEVMA AGRPQAAAVR SVSAFAARFG
VPTIADGGVQ NLGHIVKGLA LGASAVMMGS LLAGTTESPG EYFMSSEGQL VKAFRGMGSI
AVMEDKSKSG AGNNAGASRY FSENDKVKVA QGVAGSVIDR GSITQYVPYL VAGVQHSLQD
IGVQNLDALR EGVNNGTVRF EMRSASAQTE GNVHGLHTHE KKLYSS
