CBR2_MOUSE
ID CBR2_MOUSE Reviewed; 244 AA.
AC P08074;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1988, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Carbonyl reductase [NADPH] 2;
DE EC=1.1.1.184 {ECO:0000269|PubMed:7705352};
DE AltName: Full=Adipocyte protein P27;
DE Short=AP27;
DE AltName: Full=Lung carbonyl reductase;
DE Short=LCR;
DE AltName: Full=NADPH-dependent carbonyl reductase 2;
GN Name=Cbr2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CH3;
RX PubMed=2455724; DOI=10.1083/jcb.107.1.279;
RA Navre M., Ringold G.M.;
RT "A growth factor-repressible gene associated with protein kinase C-mediated
RT inhibition of adipocyte differentiation.";
RL J. Cell Biol. 107:279-286(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC
RP ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=7705352; DOI=10.1111/j.1432-1033.1995.tb20274.x;
RA Nakanishi M., Deyashiki Y., Ohshima K., Hara A.;
RT "Cloning, expression and tissue distribution of mouse tetrameric carbonyl
RT reductase. Identity with an adipocyte 27-kDa protein.";
RL Eur. J. Biochem. 228:381-387(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 SUBCELLULAR LOCATION.
RX PubMed=8040004; DOI=10.1007/bf00157764;
RA Matsuura K., Bunai Y., Ohya I., Hara A., Nakanishi M., Sawada H.;
RT "Ultrastructural localization of carbonyl reductase in mouse lung.";
RL Histochem. J. 26:311-316(1994).
RN [5]
RP MUTAGENESIS OF THR-38, AND COENZYME SPECIFICITY.
RX PubMed=8999926; DOI=10.1074/jbc.272.4.2218;
RA Nakanishi M., Matsuura K., Kaibe H., Tanaka N., Nonaka T., Mitsui Y.,
RA Hara A.;
RT "Switch of coenzyme specificity of mouse lung carbonyl reductase by
RT substitution of threonine 38 with aspartic acid.";
RL J. Biol. Chem. 272:2218-2222(1997).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42 AND SER-176, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH NADPH.
RX PubMed=8805511; DOI=10.1016/s0969-2126(96)00007-x;
RA Tanaka N., Nonaka T., Nakanishi M., Deyashiki Y., Hara A., Mitsui Y.;
RT "Crystal structure of the ternary complex of mouse lung carbonyl reductase
RT at 1.8-A resolution: the structural origin of coenzyme specificity in the
RT short-chain dehydrogenase/reductase family.";
RL Structure 4:33-45(1996).
CC -!- FUNCTION: May function in the pulmonary metabolism of endogenous
CC carbonyl compounds, such as aliphatic aldehydes and ketones derived
CC from lipid peroxidation, 3-ketosteroids and fatty aldehydes, as well as
CC in xenobiotic metabolism. {ECO:0000269|PubMed:7705352}.
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:7705352};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19259;
CC Evidence={ECO:0000269|PubMed:7705352};
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:8805511}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:8040004}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in lung, in ciliated cells,
CC non-ciliated bronchiolar cells and type-II alveolar pneumocytes
CC (PubMed:7705352, PubMed:8040004). Also detected in adipose tissue (at
CC protein level) (PubMed:7705352). Low expression in testis, heart,
CC kidney, spleen, brain and liver (PubMed:7705352).
CC {ECO:0000269|PubMed:7705352, ECO:0000269|PubMed:8040004}.
CC -!- INDUCTION: By glucocorticoids. Activated by fatty acids.
CC -!- MISCELLANEOUS: Uses both NADP and NAD as substrates. Has a strong
CC preference for NADP.
CC -!- SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; D26123; BAA05120.1; -; mRNA.
DR EMBL; X07411; CAA30309.1; -; mRNA.
DR EMBL; BC010758; AAH10758.1; -; mRNA.
DR CCDS; CCDS25756.1; -.
DR PIR; S03382; A28053.
DR RefSeq; NP_031647.1; NM_007621.2.
DR PDB; 1CYD; X-ray; 1.80 A; A/B/C/D=1-244.
DR PDBsum; 1CYD; -.
DR AlphaFoldDB; P08074; -.
DR SMR; P08074; -.
DR STRING; 10090.ENSMUSP00000026148; -.
DR iPTMnet; P08074; -.
DR PhosphoSitePlus; P08074; -.
DR jPOST; P08074; -.
DR PaxDb; P08074; -.
DR PeptideAtlas; P08074; -.
DR PRIDE; P08074; -.
DR ProteomicsDB; 279931; -.
DR DNASU; 12409; -.
DR Ensembl; ENSMUST00000026148; ENSMUSP00000026148; ENSMUSG00000025150.
DR GeneID; 12409; -.
DR KEGG; mmu:12409; -.
DR UCSC; uc007muj.2; mouse.
DR CTD; 12409; -.
DR MGI; MGI:107200; Cbr2.
DR VEuPathDB; HostDB:ENSMUSG00000025150; -.
DR eggNOG; KOG1207; Eukaryota.
DR GeneTree; ENSGT00940000154873; -.
DR HOGENOM; CLU_010194_1_0_1; -.
DR InParanoid; P08074; -.
DR OMA; HEHQPRV; -.
DR OrthoDB; 1051625at2759; -.
DR PhylomeDB; P08074; -.
DR TreeFam; TF313841; -.
DR SABIO-RK; P08074; -.
DR BioGRID-ORCS; 12409; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Cbr2; mouse.
DR EvolutionaryTrace; P08074; -.
DR PRO; PR:P08074; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P08074; protein.
DR Bgee; ENSMUSG00000025150; Expressed in right lung and 145 other tissues.
DR ExpressionAtlas; P08074; baseline and differential.
DR Genevisible; P08074; MM.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004090; F:carbonyl reductase (NADPH) activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0050038; F:L-xylulose reductase (NADP+) activity; IBA:GO_Central.
DR GO; GO:0043621; F:protein self-association; IDA:MGI.
DR GO; GO:0006006; P:glucose metabolic process; IBA:GO_Central.
DR GO; GO:0006116; P:NADH oxidation; TAS:MGI.
DR GO; GO:0005997; P:xylulose metabolic process; IBA:GO_Central.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020904; Sc_DH/Rdtase_CS.
DR InterPro; IPR002347; SDR_fam.
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 3D-structure; Direct protein sequencing; Mitochondrion; NAD; NADP;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..244
FT /note="Carbonyl reductase [NADPH] 2"
FT /id="PRO_0000054547"
FT ACT_SITE 149
FT /note="Proton acceptor"
FT BINDING 11..39
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:8805511"
FT BINDING 136
FT /ligand="substrate"
FT MOD_RES 42
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 38
FT /note="T->R: Converts the coenzyme specificity from NADP to
FT NAD."
FT /evidence="ECO:0000269|PubMed:8999926"
FT STRAND 9..14
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:1CYD"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 41..50
FT /evidence="ECO:0007829|PDB:1CYD"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 64..71
FT /evidence="ECO:0007829|PDB:1CYD"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 97..107
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 109..125
FT /evidence="ECO:0007829|PDB:1CYD"
FT STRAND 129..134
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 147..167
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:1CYD"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 185..190
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 194..203
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 212..223
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:1CYD"
FT STRAND 232..238
FT /evidence="ECO:0007829|PDB:1CYD"
FT HELIX 241..243
FT /evidence="ECO:0007829|PDB:1CYD"
SQ SEQUENCE 244 AA; 25958 MW; 4FA14C5722DD231E CRC64;
MKLNFSGLRA LVTGAGKGIG RDTVKALHAS GAKVVAVTRT NSDLVSLAKE CPGIEPVCVD
LGDWDATEKA LGGIGPVDLL VNNAALVIMQ PFLEVTKEAF DRSFSVNLRS VFQVSQMVAR
DMINRGVPGS IVNVSSMVAH VTFPNLITYS STKGAMTMLT KAMAMELGPH KIRVNSVNPT
VVLTDMGKKV SADPEFARKL KERHPLRKFA EVEDVVNSIL FLLSDRSAST SGGGILVDAG
YLAS
