URDA_EGGLE
ID URDA_EGGLE Reviewed; 606 AA.
AC C8WLE3;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 75.
DE RecName: Full=Urocanate reductase {ECO:0000303|PubMed:30401435};
DE EC=1.3.99.33 {ECO:0000250|UniProtKB:Q8CVD0, ECO:0000305|PubMed:30401435};
DE Flags: Precursor;
GN Name=urdA {ECO:0000303|PubMed:30401435};
GN OrderedLocusNames=Elen_0488 {ECO:0000312|EMBL:ACV54473.1};
OS Eggerthella lenta (strain ATCC 25559 / DSM 2243 / CCUG 17323 / JCM 9979 /
OS KCTC 3265 / NCTC 11813 / VPI 0255 / 1899 B) (Eubacterium lentum).
OC Bacteria; Actinobacteria; Coriobacteriia; Eggerthellales; Eggerthellaceae;
OC Eggerthella.
OX NCBI_TaxID=479437;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25559 / DSM 2243 / CCUG 17323 / JCM 9979 / KCTC 3265 / NCTC
RC 11813 / VPI 0255 / 1899 B;
RX PubMed=21304654; DOI=10.4056/sigs.33592;
RA Saunders E., Pukall R., Abt B., Lapidus A., Glavina Del Rio T.,
RA Copeland A., Tice H., Cheng J.F., Lucas S., Chen F., Nolan M., Bruce D.,
RA Goodwin L., Pitluck S., Ivanova N., Mavromatis K., Ovchinnikova G.,
RA Pati A., Chen A., Palaniappan K., Land M., Hauser L., Chang Y.J.,
RA Jeffries C.D., Chain P., Meincke L., Sims D., Brettin T., Detter J.C.,
RA Goker M., Bristow J., Eisen J.A., Markowitz V., Hugenholtz P.,
RA Kyrpides N.C., Klenk H.P., Han C.;
RT "Complete genome sequence of Eggerthella lenta type strain (IPP VPI
RT 0255).";
RL Stand. Genomic Sci. 1:174-182(2009).
RN [2]
RP PREDICTED FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 25559 / DSM 2243 / CCUG 17323 / JCM 9979 / KCTC 3265 / NCTC
RC 11813 / VPI 0255 / 1899 B;
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 E.lenta strain DSM 2243 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 -!- PTM: Predicted to be exported by the Tat system. The position of the
CC signal peptide cleavage has not been experimentally proven.
CC {ECO:0000255|PROSITE-ProRule:PRU00648}.
CC -!- MISCELLANEOUS: E.lenta strain DSM 2243 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; CP001726; ACV54473.1; -; Genomic_DNA.
DR RefSeq; WP_015760010.1; NC_013204.1.
DR AlphaFoldDB; C8WLE3; -.
DR SMR; C8WLE3; -.
DR STRING; 479437.Elen_0488; -.
DR EnsemblBacteria; ACV54473; ACV54473; Elen_0488.
DR GeneID; 56790922; -.
DR KEGG; ele:Elen_0488; -.
DR eggNOG; COG1053; Bacteria.
DR eggNOG; COG3976; Bacteria.
DR HOGENOM; CLU_011398_4_0_11; -.
DR OMA; VICEGAY; -.
DR OrthoDB; 153138at2; -.
DR BioCyc; ELEN479437:G1GFY-489-MON; -.
DR Proteomes; UP000001377; Chromosome.
DR GO; GO:0016020; C:membrane; IEA:InterPro.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0033765; F:steroid dehydrogenase activity, acting on the CH-CH group of donors; IEA:UniProt.
DR GO; GO:0008202; P:steroid metabolic process; IEA:UniProt.
DR Gene3D; 3.50.50.60; -; 1.
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; IPR007329; FMN-bd.
DR InterPro; IPR027477; Succ_DH/fumarate_Rdtase_cat_sf.
DR InterPro; IPR006311; TAT_signal.
DR Pfam; PF00890; FAD_binding_2; 1.
DR Pfam; PF04205; FMN_bind; 1.
DR SMART; SM00900; FMN_bind; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF56425; SSF56425; 1.
DR TIGRFAMs; TIGR01813; flavo_cyto_c; 1.
DR PROSITE; PS51318; TAT; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; FMN; Oxidoreductase; Reference proteome; Signal.
FT SIGNAL 1..40
FT /note="Tat-type signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00648"
FT CHAIN 41..606
FT /note="Urocanate reductase"
FT /id="PRO_0000446103"
FT ACT_SITE 433
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P0C278"
FT BINDING 163
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 182..183
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 190..197
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 572
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 587..588
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
SQ SEQUENCE 606 AA; 63494 MW; F0BEABC59403A357 CRC64;
MSNLSRRNFI TGGAIAALGG TLAIAGCAPK GESSSTVAGA AGEGAQAWTG TANGKGGELT
VEVITEGDSI ARINPLKSRE SYGVGTAGID VLSDLIVKNQ TLNVDMVTGA TVSSMAFLTA
VSDAVDASGM KSSEWKKREK AVPQAPEGLT TDVDVVVVGA GGAGYAAALT AAEAGKNVVL
LEKLGIVGGD TILSGGAMAV PNNWFQKRDG IEDSVEKMAE DMIVGGDHVG DPDLVNVICE
GAYGAMEWLI FNGGVAWQPY ERFFGGHSVI RSLIPEGNEG SGIICKLDKR AEGLKNLKVC
RNTKADELVQ DASGAVVGLK ATNTATGETY DFKAKAVILA AGGFGSNVEM RMKYNPEMDE
KILSTDSVGA TGDCHVMAEK IGANLIDMQY IQTYPTCDTQ TGALLYVGNM RLENRAICIN
KEGDRFVEEM ERRDVISNAI KEQTDGIGYM IFNQDGLDHT DIATVNAAEM DGLFGRGQLA
KGETIAEACE PFGIDAAELQ KTVEKWNGYC KDGADPDFNY RAALNPIEGG PYYILAYKPS
VHYTMGGLHI NTDAQVLDSD AAPIPGLFAA GEQAGHKMGT NRLGSCSITD VFVFGRVAGA
NAAALA
