URDA_STRMU
ID URDA_STRMU Reviewed; 803 AA.
AC Q8DW88;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 112.
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=SMU_180 {ECO:0000312|EMBL:AAN57955.1};
OS Streptococcus mutans serotype c (strain ATCC 700610 / UA159).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=210007;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700610 / UA159;
RX PubMed=12397186; DOI=10.1073/pnas.172501299;
RA Ajdic D.J., McShan W.M., McLaughlin R.E., Savic G., Chang J., Carson M.B.,
RA Primeaux C., Tian R., Kenton S., Jia H.G., Lin S.P., Qian Y., Li S.,
RA Zhu H., Najar F.Z., Lai H., White J., Roe B.A., Ferretti J.J.;
RT "Genome sequence of Streptococcus mutans UA159, a cariogenic dental
RT pathogen.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14434-14439(2002).
RN [2]
RP PREDICTED FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 700610 / UA159;
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 S.mutans strain UA159 may contribute
CC to the pathogenesis of type 2 diabetes by producing the microbial
CC 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: S.mutans strain UA159 is significantly more abundant in
CC subjects with type 2 diabetes (T2D) compared with subjects with normal
CC 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; AE014133; AAN57955.1; -; Genomic_DNA.
DR RefSeq; NP_720649.1; NC_004350.2.
DR RefSeq; WP_002262027.1; NC_004350.2.
DR AlphaFoldDB; Q8DW88; -.
DR SMR; Q8DW88; -.
DR STRING; 210007.SMU_180; -.
DR PRIDE; Q8DW88; -.
DR DNASU; 1029753; -.
DR EnsemblBacteria; AAN57955; AAN57955; SMU_180.
DR KEGG; smu:SMU_180; -.
DR PATRIC; fig|210007.7.peg.156; -.
DR eggNOG; COG0431; Bacteria.
DR eggNOG; COG1053; Bacteria.
DR eggNOG; COG3976; Bacteria.
DR HOGENOM; CLU_011398_4_0_9; -.
DR OMA; THIPCWL; -.
DR PhylomeDB; Q8DW88; -.
DR Proteomes; UP000002512; 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; 1.
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..803
FT /note="Urocanate reductase"
FT /id="PRO_0000446104"
FT ACT_SITE 632
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 768
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 783..784
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
SQ SEQUENCE 803 AA; 86809 MW; 1BF08F3E74FCAFB7 CRC64;
MKLIAIVGTN AKQSYNRILL QFMKRHFVQK ADIDIMEIAN VPMFNETEDQ TDLPAIQNFN
TKISQADGVI IATPEHNHTI PSSLNSLLEW LSFKVHPLDG KPLMIVGASY DVQGSSRAQL
HLRQILDAPG VNAAVMPGSE FLLGRAHQAF DEAGNLKSEA TVDFLESCFF KFLRFVQVAN
QLNEPEEVSF EAGTYQVTTQ GHNGKLPMTV TLSEEKIEKI DIDSSGESSG IADIVFTRIP
NEILEGQTLN VDAVSGASVT SNGVLDGVAR AIKLAGGNPD VLRKRPKAPS ALDKEDKTYS
TDVVIVGGGG AGLAAAARVL QAGKQVMVLE KFPALGGNTV RSGGLLNAAD PEWQKTFPAN
PGEAHNLSEL IQTDEDSIAA EYLADFKELK QQVTNYLKDP SYLFDSNILH RIQTYIGGKR
TDRNGCEVYG NYDLVKVLTD KDLDSVHWLA DIGVDFDRSE VSMPVGALWR RSHKPKQPMG
YAFIEALDTY IRKNSGTILT DTAVTDFILE NGLIKGVLAK GRNGQTITVH AQAVVLASGG
FGANTKMLQQ YNTYWSNIDD NIQTTNSPAI TGDGIRLGQS IGAALVGMGF SQMMPVSDPN
TGAIFSGLQV PPANFVMVNQ EGKRFVDEYG SRDTLSKAAI DNGGLFYLIA DENIKATAMN
TSNEKIEEQV AAGTLYRADT LESLAEQIGV DPATLVETIN NYNSYVEAGY DPEFDKGAFD
LKVEKAPFYA TPRKPATHHT MGGLKIDTQA HVIKEDGNKI PSLYAAGEVT GGIHAGNRLG
GNALADIFTF GRIAAETAVT ECC
