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Protein

Carbonyl reductase [NADPH] 1

Gene

CBR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

NADPH-dependent reductase with broad substrate specificity. Catalyzes the reduction of a wide variety of carbonyl compounds including quinones, prostaglandins, menadione, plus various xenobiotics. Catalyzes the reduction of the antitumor anthracyclines doxorubicin and daunorubicin to the cardiotoxic compounds doxorubicinol and daunorubicinol. Can convert prostaglandin E2 to prostaglandin F2-alpha. Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione.4 Publications

Catalytic activityi

R-CHOH-R' + NADP+ = R-CO-R' + NADPH.
(5Z,13E)-(15S)-9-alpha,11-alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ = (5Z,13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate + NADPH.
(13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprost-13-enoate + NADP+ = (13E)-11-alpha-hydroxy-9,15-dioxoprost-13-enoate + NADPH.

Enzyme regulationi

Inhibited by quercetin, rutenin and its derivatives.2 Publications

Kineticsi

  1. KM=30 µM for S-nitrosoglutathione2 Publications
  2. KM=22 µM for menadione2 Publications
  3. KM=309 µM for prostaglandin E22 Publications
  4. KM=173 µM for daunorubicin2 Publications
  5. KM=247 µM for NADPH2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei90NADP; via carbonyl oxygen3 Publications1
    Binding sitei106Glutathione1
    Binding sitei140Substrate1
    Active sitei194Proton acceptor1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi10 – 34NADP3 PublicationsAdd BLAST25
    Nucleotide bindingi63 – 64NADP3 Publications2
    Nucleotide bindingi194 – 198NADP3 Publications5
    Nucleotide bindingi231 – 233NADP3 Publications3

    GO - Molecular functioni

    GO - Biological processi

    • cyclooxygenase pathway Source: Reactome
    • drug metabolic process Source: UniProtKB
    • epithelial cell differentiation Source: UniProtKB
    • oxidation-reduction process Source: UniProtKB
    • vitamin K metabolic process Source: UniProtKB

    Keywordsi

    Molecular functionOxidoreductase
    LigandNADP

    Enzyme and pathway databases

    BRENDAi1.1.1.184 2681
    ReactomeiR-HSA-2162123 Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
    SABIO-RKiP16152

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carbonyl reductase [NADPH] 1 (EC:1.1.1.184)
    Alternative name(s):
    15-hydroxyprostaglandin dehydrogenase [NADP(+)] (EC:1.1.1.197)
    NADPH-dependent carbonyl reductase 1
    Prostaglandin 9-ketoreductase
    Prostaglandin-E(2) 9-reductase (EC:1.1.1.189)
    Short chain dehydrogenase/reductase family 21C member 1
    Gene namesi
    Name:CBR1
    Synonyms:CBR, CRN, SDR21C1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 21

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000159228.12
    HGNCiHGNC:1548 CBR1
    MIMi114830 gene
    neXtProtiNX_P16152

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi873
    OpenTargetsiENSG00000159228
    PharmGKBiPA26121

    Chemistry databases

    ChEMBLiCHEMBL5586
    DrugBankiDB00414 Acetohexamide
    DB00997 Doxorubicin
    DB00502 Haloperidol
    DB01046 Lubiprostone
    DB05197 Sofalcone
    DB04844 Tetrabenazine
    GuidetoPHARMACOLOGYi1383

    Polymorphism and mutation databases

    BioMutaiCBR1
    DMDMi118519

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedCombined sources
    ChainiPRO_00000546022 – 277Carbonyl reductase [NADPH] 1Add BLAST276

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylserineCombined sources1
    Modified residuei2PhosphoserineBy similarity1
    Modified residuei30PhosphoserineBy similarity1
    Modified residuei239N6-1-carboxyethyl lysine1 Publication1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiP16152
    MaxQBiP16152
    PaxDbiP16152
    PeptideAtlasiP16152
    PRIDEiP16152
    TopDownProteomicsiP16152-1 [P16152-1]

    2D gel databases

    REPRODUCTION-2DPAGEiIPI00295386
    UCD-2DPAGEiP16152

    PTM databases

    iPTMnetiP16152
    PhosphoSitePlusiP16152
    SwissPalmiP16152

    Expressioni

    Gene expression databases

    BgeeiENSG00000159228
    CleanExiHS_CBR1
    ExpressionAtlasiP16152 baseline and differential
    GenevisibleiP16152 HS

    Organism-specific databases

    HPAiHPA018433

    Interactioni

    Subunit structurei

    Monomer.3 Publications

    Protein-protein interaction databases

    BioGridi107319, 38 interactors
    DIPiDIP-33136N
    IntActiP16152, 28 interactors
    MINTiP16152
    STRINGi9606.ENSP00000290349

    Chemistry databases

    BindingDBiP16152

    Structurei

    Secondary structure

    1277
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi7 – 12Combined sources6
    Helixi16 – 28Combined sources13
    Beta strandi29 – 39Combined sources11
    Helixi40 – 52Combined sources13
    Beta strandi58 – 61Combined sources4
    Helixi67 – 81Combined sources15
    Beta strandi82 – 89Combined sources8
    Helixi103 – 114Combined sources12
    Helixi116 – 125Combined sources10
    Helixi126 – 128Combined sources3
    Beta strandi129 – 138Combined sources10
    Helixi141 – 148Combined sources8
    Helixi152 – 159Combined sources8
    Helixi165 – 180Combined sources16
    Turni184 – 188Combined sources5
    Helixi193 – 215Combined sources23
    Beta strandi222 – 227Combined sources6
    Turni234 – 236Combined sources3
    Helixi244 – 247Combined sources4
    Helixi249 – 255Combined sources7
    Beta strandi268 – 270Combined sources3
    Beta strandi273 – 275Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1WMAX-ray1.24A2-277[»]
    2PFGX-ray1.54A2-277[»]
    3BHIX-ray2.27A2-277[»]
    3BHJX-ray1.77A2-277[»]
    3BHMX-ray1.80A2-277[»]
    4Z3DX-ray1.80A/B/C/D2-277[»]
    ProteinModelPortaliP16152
    SMRiP16152
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP16152

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni95 – 97Glutathione binding3
    Regioni193 – 194Glutathione binding2

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG1208 Eukaryota
    COG1028 LUCA
    GeneTreeiENSGT00510000046499
    HOVERGENiHBG001909
    InParanoidiP16152
    KOiK00079
    OMAiSVEFSHM
    OrthoDBiEOG091G0V7L
    PhylomeDBiP16152
    TreeFamiTF329359

    Family and domain databases

    InterProiView protein in InterPro
    IPR036291 NAD(P)-bd_dom_sf
    IPR020904 Sc_DH/Rdtase_CS
    IPR002347 SDR_fam
    PfamiView protein in Pfam
    PF00106 adh_short, 1 hit
    PRINTSiPR00081 GDHRDH
    PR00080 SDRFAMILY
    SUPFAMiSSF51735 SSF51735, 1 hit
    PROSITEiView protein in PROSITE
    PS00061 ADH_SHORT, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: P16152-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MSSGIHVALV TGGNKGIGLA IVRDLCRLFS GDVVLTARDV TRGQAAVQQL
    60 70 80 90 100
    QAEGLSPRFH QLDIDDLQSI RALRDFLRKE YGGLDVLVNN AGIAFKVADP
    110 120 130 140 150
    TPFHIQAEVT MKTNFFGTRD VCTELLPLIK PQGRVVNVSS IMSVRALKSC
    160 170 180 190 200
    SPELQQKFRS ETITEEELVG LMNKFVEDTK KGVHQKEGWP SSAYGVTKIG
    210 220 230 240 250
    VTVLSRIHAR KLSEQRKGDK ILLNACCPGW VRTDMAGPKA TKSPEEGAET
    260 270
    PVYLALLPPD AEGPHGQFVS EKRVEQW
    Length:277
    Mass (Da):30,375
    Last modified:January 23, 2007 - v3
    Checksum:i51A5A495EB4F4EC3
    GO
    Isoform 2 (identifier: P16152-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         133-173: GRVVNVSSIM...TEEELVGLMN → ASCVLSAWSC...ICRCLTLGPF
         174-277: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:173
    Mass (Da):18,762
    Checksum:i0D3547831C072133
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_05905388V → I Reduced affinity for NADPH and reduced activity towards daunorubicin and prostaglandin E2. 1 PublicationCorresponds to variant dbSNP:rs1143663Ensembl.1
    Natural variantiVAR_031706131P → S1 PublicationCorresponds to variant dbSNP:rs41557318Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_054796133 – 173GRVVN…VGLMN → ASCVLSAWSCLSQNPSGGKS KPLAWFTEMSIICRCLTLGP F in isoform 2. 1 PublicationAdd BLAST41
    Alternative sequenceiVSP_054797174 – 277Missing in isoform 2. 1 PublicationAdd BLAST104

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J04056 mRNA Translation: AAA52070.1
    M62420 Genomic DNA Translation: AAA17881.1
    AB003151 Genomic DNA Translation: BAA33498.1
    AP000688 Genomic DNA Translation: BAA89424.1
    AB124848 mRNA Translation: BAE45940.1
    BT019843 mRNA Translation: AAV38646.1
    CR541708 mRNA Translation: CAG46509.1
    AK294142 mRNA Translation: BAG57468.1
    AK314879 mRNA Translation: BAG37394.1
    EF141836 Genomic DNA Translation: ABK97430.1
    AP001724 Genomic DNA Translation: BAA95508.1
    CH471079 Genomic DNA Translation: EAX09754.1
    CH471079 Genomic DNA Translation: EAX09755.1
    BC002511 mRNA Translation: AAH02511.1
    BC015640 mRNA Translation: AAH15640.1
    CCDSiCCDS13641.1 [P16152-1]
    CCDS68202.1 [P16152-2]
    PIRiA61271 RDHUCB
    RefSeqiNP_001273718.1, NM_001286789.1 [P16152-2]
    NP_001748.1, NM_001757.3 [P16152-1]
    UniGeneiHs.88778

    Genome annotation databases

    EnsembliENST00000290349; ENSP00000290349; ENSG00000159228 [P16152-1]
    ENST00000530908; ENSP00000434613; ENSG00000159228 [P16152-2]
    GeneIDi873
    KEGGihsa:873
    UCSCiuc002yvb.3 human [P16152-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiCBR1_HUMAN
    AccessioniPrimary (citable) accession number: P16152
    Secondary accession number(s): B2RBZ7, B4DFK7, Q3LHW8
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: January 23, 2007
    Last modified: May 23, 2018
    This is version 198 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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