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Identification
HMDB Protein ID HMDBP00075
Secondary Accession Numbers
  • 5304
  • HMDBP05559
Name Carbonyl reductase [NADPH] 1
Synonyms
  1. 15-hydroxyprostaglandin dehydrogenase [NADP+]
  2. NADPH-dependent carbonyl reductase 1
  3. Prostaglandin 9-ketoreductase
  4. Prostaglandin-E(2) 9-reductase
  5. 15-hydroxyprostaglandin dehydrogenase [NADP(+)]
Gene Name CBR1
Protein Type Enzyme
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function 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.
Pathways
  • Acetaminophen Action Pathway
  • Acetylsalicylic Acid Action Pathway
  • Antipyrine Action Pathway
  • Antrafenine Action Pathway
  • Arachidonic acid metabolism
  • Arachidonic Acid Metabolism
  • Bromfenac Action Pathway
  • Carprofen Action Pathway
  • Celecoxib Action Pathway
  • Chemical carcinogenesis
  • Diclofenac Action Pathway
  • Diflunisal Action Pathway
  • Dopa-responsive dystonia
  • Doxorubicin Metabolism Pathway
  • Etodolac Action Pathway
  • Etoricoxib Action Pathway
  • Fenoprofen Action Pathway
  • Flurbiprofen Action Pathway
  • Hyperphenylalaniemia due to guanosine triphosphate cyclohydrolase deficiency
  • Hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency (ptps)
  • Hyperphenylalaninemia due to dhpr-deficiency
  • Ibuprofen Action Pathway
  • Indomethacin Action Pathway
  • Ketoprofen Action Pathway
  • Ketorolac Action Pathway
  • Leukotriene C4 Synthesis Deficiency
  • Lornoxicam Action Pathway
  • Lumiracoxib Action Pathway
  • Magnesium salicylate Action Pathway
  • Mefenamic Acid Action Pathway
  • Meloxicam Action Pathway
  • Metabolism of xenobiotics by cytochrome P450
  • Nabumetone Action Pathway
  • Naproxen Action Pathway
  • Nepafenac Action Pathway
  • Oxaprozin Action Pathway
  • Phenylbutazone Action Pathway
  • Piroxicam Action Pathway
  • Pterine Biosynthesis
  • Rofecoxib Action Pathway
  • Salicylate-sodium Action Pathway
  • Salicylic Acid Action Pathway
  • Salsalate Action Pathway
  • Segawa syndrome
  • Sepiapterin reductase deficiency
  • Sulindac Action Pathway
  • Suprofen Action Pathway
  • Tenoxicam Action Pathway
  • Tiaprofenic Acid Action Pathway
  • Tolmetin Action Pathway
  • Trisalicylate-choline Action Pathway
  • Valdecoxib Action Pathway
Reactions
R-CHOH-R' + NADP → R-CO-R' + NADPH details
(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 details
(13E)-(15S)-11-alpha,15-dihydroxy-9-oxoprost-13-enoate + NADP → (13E)-11-alpha-hydroxy-9,15-dioxoprost-13-enoate + NADPH details
Prostaglandin F2a + NADP → Prostaglandin E2 + NADPH + Hydrogen Ion details
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone + NADPH + Hydrogen Ion → 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol + NADP details
1-Oxo-1H-2-benzopyran-3-carboxaldehyde → 3-(hydroxymethyl)-1H-isochromen-1-one details
3-(6,7-dimethoxy-2H-1,3-benzodioxol-5-yl)prop-2-enal → 3-(6,7-dimethoxy-2H-1,3-benzodioxol-5-yl)prop-2-en-1-ol details
Citrusal → 8-(3-hydroxy-2,2-dimethylpropyl)-7-methoxy-2H-chromen-2-one details
2-benzylheptanal → 2-benzylheptan-1-ol details
2-Methyl-3-phenylpropanal → 2-methyl-3-phenylpropan-1-ol details
3-(2-hydroxyphenyl)prop-2-enal → 2-(3-hydroxyprop-1-en-1-yl)phenol details
2-benzyloctanal → 2-benzyloctan-1-ol details
3-Phenylpropanal → 3-Phenyl-1-propanol details
3-(4-methoxyphenyl)prop-2-enal → 3-(4-methoxyphenyl)prop-2-en-1-ol details
3-(4-methoxyphenyl)propanal → 3-(4-methoxyphenyl)propan-1-ol details
3-Methyl-2-butenal → Prenol details
3-(4,7-dimethoxy-2H-1,3-benzodioxol-5-yl)prop-2-enal → 3-(4,7-dimethoxy-2H-1,3-benzodioxol-5-yl)prop-2-en-1-ol details
Mollicellin C → 7,14-dihydroxy-15-(hydroxymethyl)-6-methoxy-4,12-dimethyl-5-(3-methylbut-2-enoyl)-2,9-dioxatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one details
Mollicellin E → 13-chloro-7,14-dihydroxy-15-(hydroxymethyl)-6-methoxy-4,12-dimethyl-5-(3-methylbut-2-enoyl)-2,9-dioxatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one details
Mollicellin H → 5,14-dihydroxy-15-(hydroxymethyl)-7,12-dimethyl-6-(3-methylbut-2-en-1-yl)-2,9-dioxatricyclo[9.4.0.0³,⁸]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one details
3-Aminopropionaldehyde → 3-aminopropan-1-ol details
2-(methylamino)acetaldehyde → 2-(methylamino)ethan-1-ol details
2-{4-[(1E)-1,2-diphenylbut-1-en-1-yl]phenoxy}acetaldehyde → 2-{4-[(1E)-1,2-diphenylbut-1-en-1-yl]phenoxy}ethan-1-ol details
2-(dimethylamino)acetaldehyde → Dimethylethanolamine details
Allysine → 2-amino-6-hydroxyhexanoic acid details
2-Methylpropanal → Isobutanol details
Propanal → Propyl alcohol details
GO Classification
Biological Process
drug metabolic process
vitamin K metabolic process
Cellular Component
cytoplasm
Function
binding
catalytic activity
oxidoreductase activity
Molecular Function
oxidoreductase activity, acting on NADH or NADPH, quinone or similar compound as acceptor
15-hydroxyprostaglandin dehydrogenase (NADP+) activity
carbonyl reductase (NADPH) activity
prostaglandin-E2 9-reductase activity
nucleotide binding
Process
metabolic process
oxidation reduction
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 21
Locus 21q22.13
SNPs CBR1
Gene Sequence
>834 bp
ATGTCGTCCGGCATCCATGTAGCGCTGGTGACTGGAGGCAACAAGGGCATCGGCTTGGCC
ATCGTGCGCGACCTGTGCCGGCTGTTCTCGGGGGACGTGGTGCTCACGGCGCGGGACGTG
ACGCGGGGCCAGGCGGCCGTACAGCAGCTGCAGGCGGAGGGCCTGAGCCCGCGCTTCCAC
CAGCTGGACATCGACGATCTGCAGAGCATCCGCGCCCTGCGCGACTTCCTGCGCAAGGAG
TACGGGGGCCTGGACGTGCTGGTCAACAACGCGGGCATCGCCTTCAAGGTTGCTGATCCC
ACACCCTTTCATATTCAAGCTGAAGTGACGATGAAAACAAATTTCTTTGGTACCCGAGAT
GTGTGCACAGAATTACTCCCTCTAATAAAACCCCAAGGGAGAGTGGTGAACGTATCTAGC
ATCATGAGCGTCAGAGCCCTTAAAAGCTGCAGCCCAGAGCTGCAGCAGAAGTTCCGCAGT
GAGACCATCACTGAGGAGGAGCTGGTGGGGCTCATGAACAAGTTTGTGGAGGATACAAAG
AAGGGAGTGCACCAGAAGGAGGGCTGGCCCAGCAGCGCATACGGGGTGACGAAGATTGGC
GTCACCGTTCTGTCCAGGATCCACGCCAGGAAACTGAGTGAGCAGAGGAAAGGGGACAAG
ATCCTCCTGAATGCCTGCTGCCCAGGGTGGGTGAGAACTGACATGGCGGGACCCAAGGCC
ACCAAGAGCCCAGAAGAAGGTGCAGAGACCCCTGTGTACTTGGCCCTTTTGCCCCCAGAT
GCTGAGGGTCCCCATGGACAATTTGTTTCAGAGAAGAGAGTTGAACAGTGGTGA
Protein Properties
Number of Residues 277
Molecular Weight 30374.73
Theoretical pI 8.319
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Carbonyl reductase [NADPH] 1
MSSGIHVALVTGGNKGIGLAIVRDLCRLFSGDVVLTARDVTRGQAAVQQLQAEGLSPRFH
QLDIDDLQSIRALRDFLRKEYGGLDVLVNNAGIAFKVADPTPFHIQAEVTMKTNFFGTRD
VCTELLPLIKPQGRVVNVSSIMSVRALKSCSPELQQKFRSETITEEELVGLMNKFVEDTK
KGVHQKEGWPSSAYGVTKIGVTVLSRIHARKLSEQRKGDKILLNACCPGWVRTDMAGPKA
TKSPEEGAETPVYLALLPPDAEGPHGQFVSEKRVEQW
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P16152
UniProtKB/Swiss-Prot Entry Name CBR1_HUMAN
PDB IDs
GenBank Gene ID J04056
GeneCard ID CBR1
GenAtlas ID CBR1
HGNC ID HGNC:1548
References
General References
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  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, Nardone J, Lee K, Reeves C, Li Y, Hu Y, Tan Z, Stokes M, Sullivan L, Mitchell J, Wetzel R, Macneill J, Ren JM, Yuan J, Bakalarski CE, Villen J, Kornhauser JM, Smith B, Li D, Zhou X, Gygi SP, Gu TL, Polakiewicz RD, Rush J, Comb MJ: Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007 Dec 14;131(6):1190-203. [PubMed:18083107 ]
  4. Wermuth B, Bohren KM, Heinemann G, von Wartburg JP, Gabbay KH: Human carbonyl reductase. Nucleotide sequence analysis of a cDNA and amino acid sequence of the encoded protein. J Biol Chem. 1988 Nov 5;263(31):16185-8. [PubMed:3141401 ]
  5. Forrest GL, Akman S, Krutzik S, Paxton RJ, Sparkes RS, Doroshow J, Felsted RL, Glover CJ, Mohandas T, Bachur NR: Induction of a human carbonyl reductase gene located on chromosome 21. Biochim Biophys Acta. 1990 Apr 6;1048(2-3):149-55. [PubMed:2182121 ]
  6. Forrest GL, Akman S, Doroshow J, Rivera H, Kaplan WD: Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity. Mol Pharmacol. 1991 Oct;40(4):502-7. [PubMed:1921984 ]
  7. Watanabe K, Sugawara C, Ono A, Fukuzumi Y, Itakura S, Yamazaki M, Tashiro H, Osoegawa K, Soeda E, Nomura T: Mapping of a novel human carbonyl reductase, CBR3, and ribosomal pseudogenes to human chromosome 21q22.2. Genomics. 1998 Aug 15;52(1):95-100. [PubMed:9740676 ]
  8. Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML: The DNA sequence of human chromosome 21. Nature. 2000 May 18;405(6784):311-9. [PubMed:10830953 ]
  9. Krook M, Ghosh D, Stromberg R, Carlquist M, Jornvall H: Carboxyethyllysine in a protein: native carbonyl reductase/NADP(+)-dependent prostaglandin dehydrogenase. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):502-6. [PubMed:8421682 ]
  10. Gonzalez-Covarrubias V, Kalabus JL, Blanco JG: Inhibition of polymorphic human carbonyl reductase 1 (CBR1) by the cardioprotectant flavonoid 7-monohydroxyethyl rutoside (monoHER). Pharm Res. 2008 Jul;25(7):1730-4. doi: 10.1007/s11095-008-9592-5. Epub 2008 May 1. [PubMed:18449627 ]
  11. Tanaka M, Bateman R, Rauh D, Vaisberg E, Ramachandani S, Zhang C, Hansen KC, Burlingame AL, Trautman JK, Shokat KM, Adams CL: An unbiased cell morphology-based screen for new, biologically active small molecules. PLoS Biol. 2005 May;3(5):e128. Epub 2005 Apr 5. [PubMed:15799708 ]
  12. Bateman R, Rauh D, Shokat KM: Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct. Org Biomol Chem. 2007 Oct 21;5(20):3363-7. Epub 2007 Aug 29. [PubMed:17912391 ]
  13. Bateman RL, Rauh D, Tavshanjian B, Shokat KM: Human carbonyl reductase 1 is an S-nitrosoglutathione reductase. J Biol Chem. 2008 Dec 19;283(51):35756-62. doi: 10.1074/jbc.M807125200. Epub 2008 Sep 29. [PubMed:18826943 ]
  14. Gonzalez-Covarrubias V, Ghosh D, Lakhman SS, Pendyala L, Blanco JG: A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity. Drug Metab Dispos. 2007 Jun;35(6):973-80. Epub 2007 Mar 7. [PubMed:17344335 ]