CRB3_RAT
ID CRB3_RAT Reviewed; 277 AA.
AC B2GV72;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 10-JUN-2008, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Carbonyl reductase [NADPH] 3 {ECO:0000305};
DE EC=1.1.1.184 {ECO:0000269|PubMed:18983987};
DE AltName: Full=Monomeric carbonyl reductase 3 {ECO:0000303|PubMed:18983987};
DE AltName: Full=Quinone reductase CBR3;
DE EC=1.6.5.10 {ECO:0000250|UniProtKB:O75828};
GN Name=Cbr3 {ECO:0000312|RGD:1309728};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF TRP-230, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18983987; DOI=10.1016/j.cbi.2008.10.005;
RA Miura T., Itoh Y., Takada M., Tsutsui H., Yukimura T., Nishinaka T.,
RA Terada T.;
RT "Investigation of the role of the amino acid residue at position 230 for
RT catalysis in monomeric carbonyl reductase 3.";
RL Chem. Biol. Interact. 178:211-214(2009).
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of carbonyl compounds
CC to their corresponding alcohols. Has low NADPH-dependent oxidoreductase
CC activity (PubMed:18983987). Acts on several orthoquinones, acts as well
CC on non-quinone compounds, such as isatin or on the anticancer drug
CC oracin. Best substrates for CBR3 is 1,2- naphthoquinone, hence could
CC play a role in protection against cytotoxicity of exogenous quinones.
CC Exerts activity toward ortho-quinones but not paraquinones. No
CC endogenous substrate for CBR3 except isatin has been identified (By
CC similarity). {ECO:0000250|UniProtKB:O75828,
CC ECO:0000269|PubMed:18983987}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a secondary alcohol + NADP(+) = a ketone + H(+) + NADPH;
CC Xref=Rhea:RHEA:19257, ChEBI:CHEBI:15378, ChEBI:CHEBI:17087,
CC ChEBI:CHEBI:35681, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC EC=1.1.1.184; Evidence={ECO:0000269|PubMed:18983987};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19259;
CC Evidence={ECO:0000250|UniProtKB:O75828};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a quinone + H(+) + NADPH = a quinol + NADP(+);
CC Xref=Rhea:RHEA:46164, ChEBI:CHEBI:15378, ChEBI:CHEBI:24646,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:132124;
CC EC=1.6.5.10; Evidence={ECO:0000250|UniProtKB:O75828};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46165;
CC Evidence={ECO:0000250|UniProtKB:O75828};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.5 nM for 4-benzoylpyridine {ECO:0000269|PubMed:18983987};
CC Note=kcat is 14 min(-1) with 4-benzoylpyridine as substrate
CC (PubMed:18983987). kcat is 0.030 min(-1) with menadione as substrate
CC (PubMed:18983987). {ECO:0000269|PubMed:18983987};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O75828}.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
CC -!- CAUTION: There are conflicting results on the ability of CBR3 to
CC metabolize menadione. Although menadione was originally reported as a
CC good substrate of CBR3 (By similarity). Results of later studies showed
CC that CBR3 possesses very low or no activity toward menadione
CC (PubMed:18983987). {ECO:0000250|UniProtKB:O75828,
CC ECO:0000269|PubMed:18983987}.
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DR EMBL; AABR07033657; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474083; EDL76737.1; -; Genomic_DNA.
DR EMBL; BC166553; AAI66553.1; -; mRNA.
DR RefSeq; NP_001100580.1; NM_001107110.1.
DR AlphaFoldDB; B2GV72; -.
DR SMR; B2GV72; -.
DR STRING; 10116.ENSRNOP00000002310; -.
DR PhosphoSitePlus; B2GV72; -.
DR jPOST; B2GV72; -.
DR PaxDb; B2GV72; -.
DR PeptideAtlas; B2GV72; -.
DR PRIDE; B2GV72; -.
DR Ensembl; ENSRNOT00000002310; ENSRNOP00000002310; ENSRNOG00000001701.
DR GeneID; 304078; -.
DR KEGG; rno:304078; -.
DR UCSC; RGD:1309728; rat.
DR CTD; 874; -.
DR RGD; 1309728; Cbr3.
DR eggNOG; KOG1208; Eukaryota.
DR GeneTree; ENSGT00940000162541; -.
DR HOGENOM; CLU_010194_9_0_1; -.
DR InParanoid; B2GV72; -.
DR OMA; FRCEALT; -.
DR OrthoDB; 1259665at2759; -.
DR PhylomeDB; B2GV72; -.
DR TreeFam; TF329359; -.
DR BRENDA; 1.1.1.184; 5301.
DR Reactome; R-RNO-211945; Phase I - Functionalization of compounds.
DR Proteomes; UP000002494; Chromosome 11.
DR Proteomes; UP000234681; Chromosome 11.
DR Bgee; ENSRNOG00000001701; Expressed in stomach and 19 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0000253; F:3-keto sterol reductase activity; IDA:RGD.
DR GO; GO:0004090; F:carbonyl reductase (NADPH) activity; IDA:RGD.
DR GO; GO:0070402; F:NADPH binding; ISO:RGD.
DR GO; GO:0008753; F:NADPH dehydrogenase (quinone) activity; ISS:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0050890; P:cognition; ISO:RGD.
DR GO; GO:0042376; P:phylloquinone catabolic process; IDA:RGD.
DR CDD; cd05324; carb_red_PTCR-like_SDR_c; 1.
DR InterPro; IPR045313; CBR1-like.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR PRINTS; PR00080; SDRFAMILY.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00061; ADH_SHORT; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; NADP; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT CHAIN 2..277
FT /note="Carbonyl reductase [NADPH] 3"
FT /evidence="ECO:0000250|UniProtKB:Q8K354"
FT /id="PRO_0000455424"
FT ACT_SITE 194
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 10..34
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75828"
FT BINDING 38..42
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75828"
FT BINDING 63..64
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75828"
FT BINDING 90
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75828"
FT BINDING 140
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 194..198
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:O75828"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P16152"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48758"
FT MUTAGEN 230
FT /note="W->P: Does not affect carbonyl reductase (NADPH)
FT activity."
FT /evidence="ECO:0000269|PubMed:18983987"
SQ SEQUENCE 277 AA; 30841 MW; 05DBA2BCCD985EB0 CRC64;
MSSCSRVALV TGANKGIGFA ITRDLCRKFS GDVVLTARDE ARGRAAVKQL QAEGLSPRFH
QLDIDNPQSI RALRDFLRKE YGGLNVLVNN AGIAFRMDDP TPFDVQAEVT LKTNFFATRN
VCTELLPIMK PHGRVVNVSS LQGLKALENC SEDLQERFRC DTLTEGDLVD LMKKFVEDTK
NEVHEREGWP DSAYGVSKLG VTVLTRILAR QLDEKRKADR ILLNACCPGW VKTDMARDQG
SRTVEEGAET PVYLALLPPD ATEPHGQLVR DKVVQTW
