URDA_STREP
ID URDA_STREP Reviewed; 803 AA.
AC F8DIF2;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 1.
DT 03-AUG-2022, entry version 59.
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=HMPREF0833_10770 {ECO:0000312|EMBL:AEH55801.1};
OS Streptococcus parasanguinis (strain ATCC 15912 / DSM 6778 / CIP 104372 /
OS LMG 14537).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=760570;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15912 / DSM 6778 / CIP 104372 / LMG 14537;
RA Muzny D., Qin X., Buhay C., Dugan-Rocha S., Ding Y., Chen G., Hawes A.,
RA Holder M., Jhangiani S., Johnson A., Khan Z., Li Z., Liu W., Liu X.,
RA Perez L., Shen H., Wang Q., Watt J., Xi L., Xin Y., Zhou J., Deng J.,
RA Jiang H., Liu Y., Qu J., Song X.-Z., Zhang L., Villasana D., Johnson A.,
RA Liu J., Liyanage D., Lorensuhewa L., Robinson T., Song A., Song B.-B.,
RA Dinh H., Thornton R., Coyle M., Francisco L., Jackson L., Javaid M.,
RA Korchina V., Kovar C., Mata R., Mathew T., Ngo R., Nguyen L., Nguyen N.,
RA Okwuonu G., Ongeri F., Pham C., Simmons D., Wilczek-Boney K., Hale W.,
RA Jakkamsetti A., Pham P., Ruth R., San Lucas F., Warren J., Zhang J.,
RA Zhao Z., Zhou C., Zhu D., Lee S., Bess C., Blankenburg K., Forbes L.,
RA Fu Q., Gubbala S., Hirani K., Jayaseelan J.C., Lara F., Munidasa M.,
RA Palculict T., Patil S., Pu L.-L., Saada N., Tang L., Weissenberger G.,
RA Zhu Y., Hemphill L., Shang Y., Youmans B., Ayvaz T., Ross M.,
RA Santibanez J., Aqrawi P., Gross S., Joshi V., Fowler G., Nazareth L.,
RA Reid J., Worley K., Petrosino J., Highlander S., Gibbs R.;
RT "Complete sequence of Streptococcus parasanguinis strain ATCC 15912.";
RL Submitted (JUN-2011) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PREDICTED FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 15912 / DSM 6778 / CIP 104372 / LMG 14537;
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.parasanguinis strain ATCC 15912 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: S.parasanguinis strain ATCC 15912 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; CP002843; AEH55801.1; -; Genomic_DNA.
DR RefSeq; WP_013903794.1; NC_015678.1.
DR AlphaFoldDB; F8DIF2; -.
DR SMR; F8DIF2; -.
DR EnsemblBacteria; AEH55801; AEH55801; HMPREF0833_10770.
DR KEGG; scp:HMPREF0833_10770; -.
DR HOGENOM; CLU_011398_4_0_9; -.
DR OrthoDB; 153138at2; -.
DR Proteomes; UP000001502; 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.
FT CHAIN 1..803
FT /note="Urocanate reductase"
FT /id="PRO_0000446105"
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; 86939 MW; 4D1E9EAD5E92B661 CRC64;
MKLVAIVGTN AKQSYNRSLL QFMQRHFATK ADIEILEITD VPMFNETDDQ TDTPVIQKFN
QAISEADGVI ISTPEHNHTI PSSLNSLIEW LSFNIHPLDG KPTMIVGASY DVQGSSRAQL
HLRQILDAPG VNATVMPGSE FLLGRAHRAF DENGDLIDER TVDFLDSCFY RFLRFVSVAN
QLNLPEEIRF EPGTYHVTTE GHNGKLPMDV TVSEDRIEKI EIDSSGESSG IADVVFTRIP
AEIIEGQTLN VDAVSGASVT SNGVLDGVAR AVKQAGANPD VLRKRSKAPS ALDKEDKTYQ
ADVVIVGGGG AGLAAAAAVL QAGKKPIVVE KFPAIGGNTV RAGGPMNAPD PAWQGTFEAH
PGEANTLQEL IAIDESTIDP EYLEDFRALK VEVEQYLQDP SYLFDSTLLY RIQTYIGGKR
KDLQGHEIHG QYDLVSVLTE RALESVRWLE DIGVEFVRSE VTMPVGALWR RGHKPVQPMG
YAFISVLQKY VLENGGKILT DSPVKELLVE EGTVKGVRAE GRNGQTILVH ADAVVLASGG
FGANTKMLQK YNTYWTEIAD DIATSNTPAV TGDGILLGQS VGADLVGMGF SQMMPVSDPV
TGALFSGLQV PPANFIMVNT EGKRFVDEYG SRDKLSQAAI DNGGLFYLIA DDRIKATAYN
TSQEKIDAQV KAGTLYRADT IEELAVQIGM DPQVLADTIK KYNSYVDAGF DPEFNKGSFD
LKCEVAPFYA TPRKPAVHHT MGGLKIDTST HVLNEKGQII PGLYAAGEVA GGLHAGNRLG
GNSLTDIFTF GRIAGQTAVK ENC
