URDA_LIMF3
ID URDA_LIMF3 Reviewed; 617 AA.
AC B2GCE0;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 74.
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=LAF_0986 {ECO:0000312|EMBL:BAG27322.1};
OS Limosilactobacillus fermentum (strain NBRC 3956 / LMG 18251) (Lactobacillus
OS fermentum).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Lactobacillaceae;
OC Limosilactobacillus.
OX NCBI_TaxID=334390;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NBRC 3956 / LMG 18251;
RX PubMed=18487258; DOI=10.1093/dnares/dsn009;
RA Morita H., Toh H., Fukuda S., Horikawa H., Oshima K., Suzuki T.,
RA Murakami M., Hisamatsu S., Kato Y., Takizawa T., Fukuoka H., Yoshimura T.,
RA Itoh K., O'Sullivan D.J., McKay L.L., Ohno H., Kikuchi J., Masaoka T.,
RA Hattori M.;
RT "Comparative genome analysis of Lactobacillus reuteri and Lactobacillus
RT fermentum reveal a genomic island for reuterin and cobalamin production.";
RL DNA Res. 15:151-161(2008).
RN [2]
RP PREDICTED FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=NBRC 3956 / LMG 18251;
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.fermentum strain NBRC 3956 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.fermentum strain NBRC 3956 is significantly more
CC abundant in subjects with type 2 diabetes (T2D) compared with subjects
CC with 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; AP008937; BAG27322.1; -; Genomic_DNA.
DR RefSeq; WP_012391268.1; NC_010610.1.
DR AlphaFoldDB; B2GCE0; -.
DR SMR; B2GCE0; -.
DR EnsemblBacteria; BAG27322; BAG27322; LAF_0986.
DR KEGG; lfe:LAF_0986; -.
DR PATRIC; fig|334390.5.peg.1091; -.
DR eggNOG; COG1053; Bacteria.
DR eggNOG; COG3976; Bacteria.
DR HOGENOM; CLU_011398_4_0_9; -.
DR OMA; THIPCWL; -.
DR OrthoDB; 153138at2; -.
DR Proteomes; UP000001697; 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; 3.50.50.60; -; 2.
DR Gene3D; 3.90.700.10; -; 1.
DR InterPro; IPR003953; FAD-binding_2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR007329; FMN-bd.
DR InterPro; IPR027477; Succ_DH/fumarate_Rdtase_cat_sf.
DR Pfam; PF00890; FAD_binding_2; 2.
DR Pfam; PF04205; FMN_bind; 1.
DR SMART; SM00900; FMN_bind; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR SUPFAM; SSF56425; SSF56425; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; FMN; Oxidoreductase.
FT CHAIN 1..617
FT /note="Urocanate reductase"
FT /id="PRO_0000446102"
FT ACT_SITE 446
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P0C278"
FT BINDING 124
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 143..144
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 151..158
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 582
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
FT BINDING 597..598
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P83223"
SQ SEQUENCE 617 AA; 66121 MW; 313E4DF0F45AFEB1 CRC64;
MKAGTYKVKA KGHGSSFMPM EVTLSDDAIQ RIQVDASGET SGIADEVFKR LPAKIVKGQT
LNVDTVAGAT ISSRGVVGGV AEAITLAGGD ADEWKQRAKP EIATQAAQVE EYQTDVVVVG
AGGAGLAAAT RSLQHDKQVV ILEKFPQLGG NTTRAGGPMN AADPDWQRDF AALTGEKETL
KRLANTPLEQ IDPEYRADFE RLREQIKEYI ASGAQYLFDS NLLHEIQTYL GGKREDLAGH
EIHGRYQLVK TLVDNALDSV KWLADLGVKF DQTDVTMPVG ALWRRGHKPV EPMGYAFIHV
LGDWVTEHGA TILTETRAEH LLMENGRVVG VVAHKTDGTK VTVRAKSTFL TAGGFGANTP
MVQKYNTYWE HIDDDIATTN SPAITGDGIS LGQEAGAELT GMGFIQLMPV SDPVTGELFT
GLQTPPGNFI MVNQEGKRFV NEFAERDTLA AAAIAQGGLF YLIADDKIKE TAYNTTQESI
DAQVEAGTLF KADTLAELAG KVGMDPATLE DTINKYNSYV DAGHDPEFGK SASHLKCEVA
PFYATPRKPA IHHTMGGLAI DKHGHVLDKA ERVIAGLYSA GENAGGLHAG NRLGGNSLAD
IFTFGRLAAD TAAQENG
