Carbonyl reductase [NADPH] 1

Details

Name
Carbonyl reductase [NADPH] 1
Kind
protein
Synonyms
  • 1.1.1.184
  • 15-hydroxyprostaglandin dehydrogenase [NADP(+)]
  • 20-beta-hydroxysteroid dehydrogenase
  • Alcohol dehydrogenase [NAD(P)+] CBR1
  • CBR
  • CRN
  • NADPH-dependent carbonyl reductase 1
  • PG-9-KR
  • Prostaglandin 9-ketoreductase
  • Prostaglandin-E(2) 9-reductase
  • SDR21C1
  • Short chain dehydrogenase/reductase family 21C member 1
Gene Name
CBR1
UniProtKB Entry
P16152Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0006005|Carbonyl reductase [NADPH] 1
MSSGIHVALVTGGNKGIGLAIVRDLCRLFSGDVVLTARDVTRGQAAVQQLQAEGLSPRFH
QLDIDDLQSIRALRDFLRKEYGGLDVLVNNAGIAFKVADPTPFHIQAEVTMKTNFFGTRD
VCTELLPLIKPQGRVVNVSSIMSVRALKSCSPELQQKFRSETITEEELVGLMNKFVEDTK
KGVHQKEGWPSSAYGVTKIGVTVLSRIHARKLSEQRKGDKILLNACCPGWVRTDMAGPKA
TKSPEEGAETPVYLALLPPDAEGPHGQFVSEKRVEQW
Number of residues
277
Molecular Weight
30374.73
Theoretical pI
8.49
GO Classification
Functions
15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity / alcohol dehydrogenase (NADP+) activity / oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor / prostaglandin E2 9-reductase activity / S-nitrosoglutathione reductase (NADPH) activity
Processes
glucocorticoid metabolic process / positive regulation of reactive oxygen species metabolic process / xenobiotic metabolic process
General 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 (PubMed:15799708, PubMed:17344335, PubMed:17912391, PubMed:18449627, PubMed:18826943, PubMed:1921984, PubMed:7005231). Can convert prostaglandin E to prostaglandin F2-alpha (By similarity). Can bind glutathione, which explains its higher affinity for glutathione-conjugated substrates. Catalyzes the reduction of S-nitrosoglutathione (PubMed:17344335, PubMed:18826943). In addition, participates in the glucocorticoid metabolism by catalyzing the NADPH-dependent cortisol/corticosterone into 20beta-dihydrocortisol (20b-DHF) or 20beta-corticosterone (20b-DHB), which are weak agonists of NR3C1 and NR3C2 in adipose tissue (PubMed:28878267)
Specific Function
15-hydroxyprostaglandin dehydrogenase (NADP+) activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0012150|Carbonyl reductase [NADPH] 1 (CBR1)
ATGTCGTCCGGCATCCATGTAGCGCTGGTGACTGGAGGCAACAAGGGCATCGGCTTGGCC
ATCGTGCGCGACCTGTGCCGGCTGTTCTCGGGGGACGTGGTGCTCACGGCGCGGGACGTG
ACGCGGGGCCAGGCGGCCGTACAGCAGCTGCAGGCGGAGGGCCTGAGCCCGCGCTTCCAC
CAGCTGGACATCGACGATCTGCAGAGCATCCGCGCCCTGCGCGACTTCCTGCGCAAGGAG
TACGGGGGCCTGGACGTGCTGGTCAACAACGCGGGCATCGCCTTCAAGGTTGCTGATCCC
ACACCCTTTCATATTCAAGCTGAAGTGACGATGAAAACAAATTTCTTTGGTACCCGAGAT
GTGTGCACAGAATTACTCCCTCTAATAAAACCCCAAGCATCCTGCGTACTGTCTGCATGG
TCATGCCTCTCCCAAAATCCTTCAGGAGGAAAGTCCAAGCCCTTAGCATGGTTCACAGAG
ATGTCCATAATCTGCCGCTGCTTAACTCTGGGCCCATTTTAA
Chromosome Location
21
Locus
21q22.12
External Identifiers
ResourceLink
UniProtKB IDP16152
UniProtKB Entry NameCBR1_HUMAN
GenBank Gene IDJ04056
GeneCard IDCBR1
GenAtlas IDCBR1
HGNC IDHGNC:1548
PDB ID(s)1WMA, 2PFG, 3BHI, 3BHJ, 3BHM, 4Z3D
KEGG IDhsa:873
IUPHAR/Guide To Pharmacology ID1383
NCBI Gene ID873
General References
  1. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
  4. 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. [Article]
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  6. 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. [Article]
  7. 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. [Article]
  8. 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. [Article]
  9. 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. [Article]
  10. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  11. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  12. 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. [Article]
  13. 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. [Article]
  14. 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. [Article]
  15. 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. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Heptaethylene glycolexperimentalunknowntargetDetails
2-(2-{2-[2-(2-{2-[2-(2-Ethoxy-Ethoxy)-Ethoxy]-Ethoxy}-Ethoxy)-Ethoxy]-Ethoxy}-Ethoxy)-Ethanol, Polyethyleneglycol Peg400experimentalunknowntargetDetails
3-(4-Amino-1-Tert-Butyl-1h-Pyrazolo[3,4-D]Pyrimidin-3-Yl)PhenolexperimentalunknowntargetligandDetails
Lubiprostoneapproved, investigationalunknownenzymesubstrateDetails
Acetohexamideapproved, investigational, withdrawnunknownenzymesubstrateDetails
3-(4-Amino-1-Tert-Butyl-1h-Pyrazolo[3,4-D]Pyrimidin-3-Yl)PhenolexperimentalunknownenzymebinderDetails
HaloperidolapprovedunknownenzymesubstrateDetails
SofalconeinvestigationalunknownenzymeinhibitorDetails
Tetrabenazineapproved, investigationalunknownenzymesubstrateDetails
Doxorubicinapproved, investigationalnoenzymesubstrateDetails
Deutetrabenazineapproved, investigationalunknownenzymesubstrateDetails
Rutinapproved, experimental, investigationalunknowntargetDetails
ResveratrolinvestigationalunknowntargetinhibitorDetails
Curcuminapproved, investigationalunknowntargetDetails
Quercetinexperimental, investigationalunknowntargetDetails
AmrubicininvestigationalunknownenzymesubstrateDetails
Curcumin sulfateexperimentalunknowntargetDetails
FenofibrateapprovedunknownenzymesubstrateDetails
OxcarbazepineapprovedunknownenzymesubstrateDetails
LoxoprofenapprovednoenzymesubstrateDetails
DaunorubicinapprovedunknownenzymesubstrateDetails
N-6022investigationalyestargetinhibitorDetails