URDA_LACPL
ID URDA_LACPL Reviewed; 812 AA.
AC F9UNH3;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Urocanate reductase {ECO:0000303|PubMed:30401435};
DE EC=1.3.99.33 {ECO:0000250|UniProtKB:Q8CVD0, ECO:0000305|PubMed:30401435};
GN Name=urdA {ECO:0000303|PubMed:30401435};
GN OrderedLocusNames=lp_1425 {ECO:0000312|EMBL:CCC78762.1};
OS Lactiplantibacillus plantarum (strain ATCC BAA-793 / NCIMB 8826 / WCFS1)
OS (Lactobacillus plantarum).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Lactobacillaceae;
OC Lactiplantibacillus.
OX NCBI_TaxID=220668;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-793 / NCIMB 8826 / WCFS1;
RX PubMed=12566566; DOI=10.1073/pnas.0337704100;
RA Kleerebezem M., Boekhorst J., van Kranenburg R., Molenaar D., Kuipers O.P.,
RA Leer R., Tarchini R., Peters S.A., Sandbrink H.M., Fiers M.W.E.J.,
RA Stiekema W., Klein Lankhorst R.M., Bron P.A., Hoffer S.M.,
RA Nierop Groot M.N., Kerkhoven R., De Vries M., Ursing B., De Vos W.M.,
RA Siezen R.J.;
RT "Complete genome sequence of Lactobacillus plantarum WCFS1.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:1990-1995(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=ATCC BAA-793 / NCIMB 8826 / WCFS1;
RX PubMed=22156394; DOI=10.1128/jb.06275-11;
RA Siezen R.J., Francke C., Renckens B., Boekhorst J., Wels M.,
RA Kleerebezem M., van Hijum S.A.;
RT "Complete resequencing and reannotation of the Lactobacillus plantarum
RT WCFS1 genome.";
RL J. Bacteriol. 194:195-196(2012).
RN [3]
RP PREDICTED FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC BAA-793 / NCIMB 8826 / WCFS1;
RX PubMed=30401435; DOI=10.1016/j.cell.2018.09.055;
RA Koh A., Molinaro A., Staahlman M., Khan M.T., Schmidt C.,
RA Manneraas-Holm L., Wu H., Carreras A., Jeong H., Olofsson L.E., Bergh P.O.,
RA Gerdes V., Hartstra A., de Brauw M., Perkins R., Nieuwdorp M.,
RA Bergstroem G., Baeckhed F.;
RT "Microbially produced imidazole propionate impairs insulin signaling
RT through mTORC1.";
RL Cell 175:947-961(2018).
CC -!- FUNCTION: Catalyzes the two-electron reduction of urocanate to
CC dihydrourocanate (also named imidazole propionate or deamino-
CC histidine). Dihydrourocanate is present at higher concentrations in
CC subjects with type 2 diabetes, and directly impairs glucose tolerance
CC and insulin signaling at the level of insulin receptor substrate (IRS)
CC through activation of p38 gamma (MAPK12)-p62-mTORC1. Therefore, the
CC UrdA enzyme from the gut bacteria L.plantarum strain WCFS1, may
CC contribute to the pathogenesis of type 2 diabetes by producing the
CC microbial metabolite dihydrourocanate. {ECO:0000305|PubMed:30401435}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=A + dihydrourocanate = AH2 + urocanate; Xref=Rhea:RHEA:36059,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:17499, ChEBI:CHEBI:27247,
CC ChEBI:CHEBI:72991; EC=1.3.99.33;
CC Evidence={ECO:0000250|UniProtKB:Q8CVD0, ECO:0000305|PubMed:30401435};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q8CVD0};
CC Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:Q8CVD0};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q8CVD0};
CC Note=Binds 1 FMN covalently per subunit.
CC {ECO:0000250|UniProtKB:Q8CVD0};
CC -!- MISCELLANEOUS: L.plantarum strain WCFS1 is significantly more abundant
CC in subjects with type 2 diabetes (T2D) compared with subjects with
CC normal glucose tolerance (NGT). {ECO:0000305|PubMed:30401435}.
CC -!- SIMILARITY: Belongs to the FAD-dependent oxidoreductase 2 family.
CC FRD/SDH subfamily. {ECO:0000305}.
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DR EMBL; AL935263; CCC78762.1; -; Genomic_DNA.
DR RefSeq; WP_011101399.1; NC_004567.2.
DR RefSeq; YP_004889276.1; NC_004567.2.
DR AlphaFoldDB; F9UNH3; -.
DR SMR; F9UNH3; -.
DR STRING; 220668.lp_1425; -.
DR DNASU; 1062454; -.
DR EnsemblBacteria; CCC78762; CCC78762; lp_1425.
DR KEGG; lpl:lp_1425; -.
DR PATRIC; fig|220668.9.peg.1195; -.
DR eggNOG; COG0431; Bacteria.
DR eggNOG; COG1053; Bacteria.
DR eggNOG; COG3976; Bacteria.
DR HOGENOM; CLU_011398_4_0_9; -.
DR OMA; RRGHKPM; -.
DR PhylomeDB; F9UNH3; -.
DR BioCyc; LPLA220668:G1GW0-1223-MON; -.
DR Proteomes; UP000000432; Chromosome.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0008152; P:metabolic process; IEA:UniProt.
DR Gene3D; 3.40.50.360; -; 1.
DR Gene3D; 3.50.50.60; -; 2.
DR Gene3D; 3.90.700.10; -; 1.
DR InterPro; IPR003953; FAD-binding_2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR010960; Flavocytochrome_c.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR InterPro; IPR007329; FMN-bd.
DR InterPro; IPR005025; FMN_Rdtase-like.
DR InterPro; IPR027477; Succ_DH/fumarate_Rdtase_cat_sf.
DR Pfam; PF00890; FAD_binding_2; 2.
DR Pfam; PF04205; FMN_bind; 1.
DR Pfam; PF03358; FMN_red; 1.
DR SMART; SM00900; FMN_bind; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF52218; SSF52218; 1.
DR SUPFAM; SSF56425; SSF56425; 1.
DR TIGRFAMs; TIGR01813; flavo_cyto_c; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; FMN; Oxidoreductase; Reference proteome.
FT CHAIN 1..812
FT /note="Urocanate reductase"
FT /id="PRO_0000446106"
FT ACT_SITE 636
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P0C278"
FT BINDING 311
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 330..331
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 338..345
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 772
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 787..788
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
SQ SEQUENCE 812 AA; 87232 MW; 2154DC2B9F842929 CRC64;
MKFVGIVGTN AQHSYNRMLL EFMQRHFATQ AEIEILELTD VPMFDESNDQ TDSTIIQNFA
TKIATADGVI IASPEHNHSV PSALKSIIEW LSFKIHPLDG QAVMIVGASY SVQGSSRAQL
HLRQILDAPG VNASVMPGSE FLLGRAQTAF DDQGNLKVQG TVDFLDSCFA KFQKFATIVA
EMRAPEALSF APGTYQVTAT GHNGELPMRV TLSADRIENI EIDTSSETQG IADVAFERIP
KEIIAGQTLA VDAISGASIT SHGVIDGVAR AVKEAGANPD DLKKRRATKQ VAQPAVKEVT
TDVVVVGAGG AGMTAAAKVL QAGHQAVVLE KFPAVGGNTV RAGGPMNAAD PDWQRQFAAL
PGEKQTLKDL SERDESTIAP EYRADFRKLK QQIDAYLTAN TNQKGTLFDS TLLHRIQTYL
GGQRTDLNGQ EIHGQYDLVK ELTDNALDSV KWLQSIGVKF DESQVTMPVG AIWRRGHKPM
GDLGFAYIKT LRAFVEQQGG TIMTETPVKE LLVTDGQVRG VIATNAAHEK VIVHADAVIL
ASGGFAANTK MLQKYNTYWT AIDDDVKTTN SPAMTGDGIR LGTSVGAALV GMGFSQMMPV
SDPETGELFS GLQVPPANFV MVNQQGKRFV NEYGSRDELT QAAIDNGSLF YLIADDEIKK
TAYNTTQAKI DQQVANGTLF RADTLTDLAQ QIGMDPAALT KTIADYNRYV DAGEDPEFHK
TAFDLKVAVA PFYATPRKPA THHTMGGLKI DSDAHVLNTD GQVIDGLYAA GEVAGGIHAG
NRLGGNSLSD IFTFGRIAAA HAVAEHVDPV TA
