P16152 (CBR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Gene names

Name:	CBR1
Synonyms:	CBR, CRN

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	277 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.15 Ref.17 Ref.18 Ref.19
Catalytic activity	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 regulation	Inhibited by quercetin, rutenin and its derivatives. Ref.15 Ref.20
Subunit structure	Monomer.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Biophysicochemical properties	Kinetic parameters: KM=30 µM for S-nitrosoglutathione Ref.19 Ref.20 KM=22 µM for menadione KM=309 µM for prostaglandin E2 KM=173 µM for daunorubicin KM=247 µM for NADPH

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	drug metabolic process Inferred from direct assay Ref.15. Source: UniProtKB vitamin K metabolic process Inferred from direct assay Ref.15. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	15-hydroxyprostaglandin dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: EC carbonyl reductase (NADPH) activity Inferred from direct assay Ref.15. Source: UniProtKB nucleotide binding Inferred from electronic annotation. Source: InterPro prostaglandin-E2 9-reductase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 277

276

Carbonyl reductase [NADPH] 1

PRO_0000054602

Regions

Nucleotide binding

10 – 34

25

NADP

Nucleotide binding

63 – 64

2

NADP

Nucleotide binding

194 – 198

5

NADP

Nucleotide binding

231 – 233

3

NADP

Region

95 – 97

3

Glutathione binding

Region

193 – 194

2

Glutathione binding

Sites

Active site

194

1

Proton acceptor

Binding site

90

1

NADP; via carbonyl oxygen

Binding site

106

1

Glutathione

Binding site

140

1

Substrate

Amino acid modifications

Modified residue

2

1

N-acetylserine

Modified residue

194

1

Phosphotyrosine Ref.14

Modified residue

239

1

N6-1-carboxyethyl lysine Ref.13

Natural variations

Natural variant

88

1

V → I Reduced affinity for NADPH and reduced activity towards daunorubicin and prostaglandin E2. Ref.20
Corresponds to variant rs1143663 [ dbSNP | Ensembl ].

VAR_059053

Natural variant

131

1

P → S. Ref.9
Corresponds to variant rs41557318 [ dbSNP | Ensembl ].

VAR_031706

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

277

Helix Strand Turn

Details...

Beta strand

7 – 12

6

Helix

16 – 28

13

Beta strand

29 – 39

11

Helix

40 – 52

13

Beta strand

58 – 61

4

Helix

67 – 81

15

Beta strand

82 – 89

8

Helix

103 – 114

12

Helix

116 – 125

10

Helix

126 – 128

3

Beta strand

129 – 138

10

Helix

141 – 148

8

Helix

152 – 159

8

Helix

165 – 180

16

Turn

184 – 188

5

Helix

193 – 215

23

Beta strand

222 – 227

6

Turn

234 – 236

3

Helix

244 – 247

4

Helix

249 – 255

7

Beta strand

268 – 270

3

Beta strand

273 – 275

3

Sequences

	Sequence		Length	Mass (Da)
	P16152 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 51A5A495EB4F4EC3	FASTA	277	30,375
	10 20 30 40 50 60 MSSGIHVALV TGGNKGIGLA IVRDLCRLFS GDVVLTARDV TRGQAAVQQL QAEGLSPRFH 70 80 90 100 110 120 QLDIDDLQSI RALRDFLRKE YGGLDVLVNN AGIAFKVADP TPFHIQAEVT MKTNFFGTRD 130 140 150 160 170 180 VCTELLPLIK PQGRVVNVSS IMSVRALKSC SPELQQKFRS ETITEEELVG LMNKFVEDTK 190 200 210 220 230 240 KGVHQKEGWP SSAYGVTKIG VTVLSRIHAR KLSEQRKGDK ILLNACCPGW VRTDMAGPKA 250 260 270 TKSPEEGAET PVYLALLPPD AEGPHGQFVS EKRVEQW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human carbonyl reductase. Nucleotide sequence analysis of a cDNA and amino acid sequence of the encoded protein." Wermuth B., Bohren K.M., Heinemann G., von Wartburg J.-P., Gabbay K.H. J. Biol. Chem. 263:16185-16188(1988) [PubMed: 3141401] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Placenta.
[2]	"Induction of a human carbonyl reductase gene located on chromosome 21." Forrest G.L., Akman S., Krutzik S., Paxton R.J., Sparkes R.S., Doroshow J., Felsted R.L., Mohandas T., Bachur N.R. Biochim. Biophys. Acta 1048:149-155(1990) [PubMed: 2182121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Mammary gland.
[3]	"Genomic sequence and expression of a cloned human carbonyl reductase gene with daunorubicin reductase activity." Forrest G.L., Akman S., Doroshow J., Rivera H., Kaplan W.D. Mol. Pharmacol. 40:502-507(1991) [PubMed: 1921984] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Mapping of a novel human carbonyl reductase, CBR3, and ribosomal pseudogenes to human chromosome 21q22.2." Watanabe K., Sugawara C., Ono A., Fukuzumi Y., Itakura S., Yamazaki M., Tashiro H., Osoegawa K., Soeda E., Nomura T. Genomics 52:95-100(1998) [PubMed: 9740676] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Human fetal brain carbonyl reductases." Terada T., Mizobuchi H. Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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 T.-O., 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. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Hippocampus.
[9]	SeattleSNPs variation discovery resource Submitted (NOV-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-131.
[10]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., 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., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[13]	"Carboxyethyllysine in a protein: native carbonyl reductase/NADP(+)-dependent prostaglandin dehydrogenase." Krook M., Ghosh D., Stroemberg R., Carlquist M., Joernvall H. Proc. Natl. Acad. Sci. U.S.A. 90:502-506(1993) [PubMed: 8421682] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, N6-1-CARBOXYETHYLATION AT LYS-239.
[14]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." 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 J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-194, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[15]	"Inhibition of polymorphic human carbonyl reductase 1 (CBR1) by the cardioprotectant flavonoid 7-monohydroxyethyl rutoside (monoHER)." Gonzalez-Covarrubias V., Kalabus J.L., Blanco J.G. Pharm. Res. 25:1730-1734(2008) [PubMed: 18449627] [Abstract] Cited for: ENZYME REGULATION, FUNCTION.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]	"An unbiased cell morphology-based screen for new, biologically active small molecules." Tanaka M., Bateman R., Rauh D., Vaisberg E., Ramachandani S., Zhang C., Hansen K.C., Burlingame A.L., Trautman J.K., Shokat K.M., Adams C.L. PLoS Biol. 3:E128-E128(2005) [PubMed: 15799708] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.24 ANGSTROMS) OF 2-276 IN COMPLEX WITH THE SYNTHETIC INHIBITOR HYDROXY-PP AND NADP, MASS SPECTROMETRY, PARTIAL PROTEIN SEQUENCE, FUNCTION.
[18]	"Glutathione traps formaldehyde by formation of a bicyclo[4.4.1]undecane adduct." Bateman R., Rauh D., Shokat K.M. Org. Biomol. Chem. 5:3363-3367(2007) [PubMed: 17912391] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 2-277 IN COMPLEX WITH NADP AND FORMALDEHYDE-GLUTATHIONE ADDUCT, FUNCTION.
[19]	"Human carbonyl reductase 1 is an S-nitrosoglutathione reductase." Bateman R.L., Rauh D., Tavshanjian B., Shokat K.M. J. Biol. Chem. 283:35756-35762(2008) [PubMed: 18826943] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 2-277 IN COMPLEX WITH NADP, SUBSTRATE ANALOGS, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[20]	"A functional genetic polymorphism on human carbonyl reductase 1 (CBR1 V88I) impacts on catalytic activity and NADPH binding affinity." Gonzalez-Covarrubias V., Ghosh D., Lakhman S.S., Pendyala L., Blanco J.G. Drug Metab. Dispos. 35:973-980(2007) [PubMed: 17344335] [Abstract] Cited for: VARIANT ILE-88, CHARACTERIZATION OF VARIANT ILE-88, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
AK314879 mRNA. Translation: BAG37394.1.
EF141836 Genomic DNA. Translation: ABK97430.1.
AP001724 Genomic DNA. Translation: BAA95508.1.
CH471079 Genomic DNA. Translation: EAX09755.1.
BC002511 mRNA. Translation: AAH02511.1.
BC015640 mRNA. Translation: AAH15640.1.

IPI

IPI00295386.

PIR

RDHUCB. A61271.

RefSeq

NP_001748.1. NM_001757.2.

UniGene

Hs.606200.
Hs.88778.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WMA	X-ray	1.24	A	2-276	[»]
2PFG	X-ray	1.54	A	2-277	[»]
3BHI	X-ray	2.27	A	2-277	[»]
3BHJ	X-ray	1.77	A	2-277	[»]
3BHM	X-ray	1.80	A	2-277	[»]

ProteinModelPortal

P16152.

SMR

P16152. Positions 3-277.

ModBase

Search...

Protein-protein interaction databases

IntAct

P16152. 8 interactions.

MINT

MINT-1418935.

STRING

P16152.

PTM databases

PhosphoSite

P16152.

Polymorphism databases

DMDM

118519.

2D gel databases

REPRODUCTION-2DPAGE

IPI00295386.

UCD-2DPAGE

P16152.

Proteomic databases

PeptideAtlas

P16152.

PRIDE

P16152.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000290349; ENSP00000290349; ENSG00000159228.

GeneID

873.

KEGG

hsa:873.

UCSC

uc002yvb.1. human.

Organism-specific databases

CTD

873.

GeneCards

GC21P037442.

H-InvDB

HIX0016099.

HGNC

HGNC:1548. CBR1.

HPA

HPA018433.

MIM

114830. gene.

neXtProt

NX_P16152.

PharmGKB

PA26121.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15925.

GeneTree

ENSGT00510000046499.

HOGENOM

HBG750976.

HOVERGEN

HBG001909.

InParanoid

P16152.

OMA

DTGVWLA.

OrthoDB

EOG4BP1CB.

PhylomeDB

P16152.

Enzyme and pathway databases

BRENDA

1.1.1.184. 2681.

Gene expression databases

ArrayExpress

P16152.

Bgee

P16152.

CleanEx

HS_CBR1.

Genevestigator

P16152.

GermOnline

ENSG00000159228. Homo sapiens.

Family and domain databases

InterPro

IPR002198. DH_sc/Rdtase_SDR.
IPR002347. Glc/ribitol_DH.
IPR016040. NAD(P)-bd_dom.
IPR020904. Sc_DH/Rdtase_CS.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

KO

K00079.

Pfam

PF00106. adh_short. 1 hit.
[Graphical view]

PRINTS

PR00081. GDHRDH.
PR00080. SDRFAMILY.

PROSITE

PS00061. ADH_SHORT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00414. Acetohexamide.
DB01046. Lubiprostone.

NextBio

3634.

SOURCE

Search...

Entry information

Entry name

CBR1_HUMAN

Accession

Primary (citable) accession number: P16152
Secondary accession number(s): B2RBZ7, Q3LHW8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 138 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.