O75828 (CBR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Carbonyl reductase [NADPH] 3
EC=1.1.1.184

Alternative name(s):
NADPH-dependent carbonyl reductase 3

Gene names

Name:

CBR3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	277 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Has low NADPH-dependent oxidoreductase activity towards 4-benzoylpyridine and menadione (in vitro). Ref.9
Catalytic activity	R-CHOH-R' + NADP+ = R-CO-R' + NADPH.
Subcellular location	Cytoplasm Ref.9.
Tissue specificity	Detected in ovary, pancreas, intestine, colon, kidney, brain, thymus, lung, heart, liver, spleen, leukocyte, prostate and testis. Ref.9
Sequence similarities	Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Biophysicochemical properties	Kinetic parameters: KM=25 µM for menadione (Ref.12) Ref.9 Ref.12 KM=43 µM for menadione (Ref.9) KM=90 µM for NADPH (Ref.12) KM=38 µM for NADPH (Ref.9) pH dependence: Optimum pH is 5.5-7.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	NADP
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	phylloquinone catabolic process Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from direct assay Ref.9. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular_function	3-keto sterol reductase activity Inferred from electronic annotation. Source: Compara NADPH binding Inferred from direct assay Ref.9. Source: UniProtKB carbonyl reductase (NADPH) activity Inferred from direct assay Ref.9. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 277

277

Carbonyl reductase [NADPH] 3

PRO_0000054608

Regions

Nucleotide binding

10 – 34

25

NADP

Nucleotide binding

38 – 42

5

NADP

Nucleotide binding

63 – 64

2

NADP

Nucleotide binding

194 – 198

5

NADP

Sites

Active site

194

1

Proton acceptor By similarity

Binding site

90

1

NADP; via carbonyl oxygen

Binding site

140

1

Substrate By similarity

Binding site

239

1

NADP

Natural variations

Natural variant

4

1

C → Y. Ref.5
Corresponds to variant rs8133052 [ dbSNP | Ensembl ].

VAR_033868

Natural variant

84

1

L → V. Ref.5
Corresponds to variant rs9282628 [ dbSNP | Ensembl ].

VAR_033869

Natural variant

93

1

V → I.
Corresponds to variant rs2835285 [ dbSNP | Ensembl ].

VAR_033870

Natural variant

131

1

P → S. Ref.5
Corresponds to variant rs16993929 [ dbSNP | Ensembl ].

VAR_033871

Natural variant

235

1

M → L. Ref.5
Corresponds to variant rs4987121 [ dbSNP | Ensembl ].

VAR_033872

Natural variant

244

1

V → M Increased catalytic activity. Ref.5 Ref.12
Corresponds to variant rs1056892 [ dbSNP | Ensembl ].

VAR_033873

Secondary structure

1

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277

Helix Strand Turn

Details...

Beta strand

7 – 12

6

Helix

16 – 28

13

Beta strand

30 – 39

10

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

142 – 149

8

Helix

152 – 159

8

Helix

165 – 180

16

Turn

184 – 188

5

Helix

193 – 215

23

Helix

217 – 219

3

Beta strand

222 – 227

6

Beta strand

237 – 239

3

Helix

241 – 247

7

Helix

249 – 255

7

Beta strand

268 – 270

3

Beta strand

273 – 275

3

Sequences

	Sequence		Length	Mass (Da)
	O75828 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 8D39D6B99CFE5389	FASTA	277	30,850
	10 20 30 40 50 60 MSSCSRVALV TGANRGIGLA IARELCRQFS GDVVLTARDV ARGQAAVQQL QAEGLSPRFH 70 80 90 100 110 120 QLDIDDLQSI RALRDFLRKE YGGLNVLVNN AAVAFKSDDP MPFDIKAEMT LKTNFFATRN 130 140 150 160 170 180 MCNELLPIMK PHGRVVNISS LQCLRAFENC SEDLQERFHS ETLTEGDLVD LMKKFVEDTK 190 200 210 220 230 240 NEVHEREGWP NSPYGVSKLG VTVLSRILAR RLDEKRKADR ILVNACCPGP VKTDMDGKDS 250 260 270 IRTVEEGAET PVYLALLPPD ATEPQGQLVH DKVVQNW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"Homo sapiens mRNA for NADPH-dependent carbonyl reductase 3, complete cds." Shimizu N., Kudoh J., Shibuya K. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal kidney.
[3]	"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.
[4]	"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].
[5]	SeattleSNPs variation discovery resource Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-4; VAL-84; SER-131; LEU-235 AND MET-244.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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].
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[9]	"Different functions between human monomeric carbonyl reductase 3 and carbonyl reductase 1." Miura T., Nishinaka T., Terada T. Mol. Cell. Biochem. 315:113-121(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
[10]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Crystal structure of human carbonyl reductase 3, complexed with NADP+." Structural genomics consortium (SGC) Submitted (FEB-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 6-276 IN COMPLEX WITH NADP.
[12]	"Functional significance of a natural allelic variant of human carbonyl reductase 3 (CBR3)." Lakhman S.S., Ghosh D., Blanco J.G. Drug Metab. Dispos. 33:254-257(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT MET-244, BIOPHYSICOCHEMICAL PROPERTIES.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB004854 mRNA. Translation: BAA33500.1.
AB003151 Genomic DNA. Translation: BAA34207.1.
AB041012 mRNA. Translation: BAD74062.1.
AB124847 mRNA. Translation: BAE45939.1.
CR541709 mRNA. Translation: CAG46510.1.
EF462915 Genomic DNA. Translation: ABO43035.1.
AP000689 Genomic DNA. Translation: BAA89425.1.
AP001725 Genomic DNA. Translation: BAA95547.1.
CH471079 Genomic DNA. Translation: EAX09747.1.
BC002812 mRNA. Translation: AAH02812.1.

IPI

IPI00290462.

RefSeq

NP_001227.1. NM_001236.3.

UniGene

Hs.154510.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HRB	X-ray	1.90	A	6-276	[»]

ProteinModelPortal

O75828.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75828. 5 interactions.

MINT

MINT-1412792.

STRING

9606.ENSP00000290354.

PTM databases

PhosphoSite

O75828.

2D gel databases

REPRODUCTION-2DPAGE

IPI00290462.

Proteomic databases

PaxDb

O75828.

PeptideAtlas

O75828.

PRIDE

O75828.

Protocols and materials databases

DNASU

874.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000290354; ENSP00000290354; ENSG00000159231.

GeneID

874.

KEGG

hsa:874.

UCSC

uc002yve.3. human.

Organism-specific databases

CTD

874.

GeneCards

GC21P037507.

HGNC

HGNC:1549. CBR3.

HPA

HPA018434.

MIM

603608. gene.

neXtProt

NX_O75828.

PharmGKB

PA26122.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1028.

HOVERGEN

HBG001909.

InParanoid

O75828.

KO

K00084.

OMA

EGWPDSA.

OrthoDB

EOG4BP1CB.

PhylomeDB

O75828.

Enzyme and pathway databases

SABIO-RK

O75828.

Gene expression databases

Bgee

O75828.

CleanEx

HS_CBR3.

Genevestigator

O75828.

GermOnline

ENSG00000159231. Homo sapiens.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.

InterPro

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

Pfam

PF00106. adh_short. 1 hit.
[Graphical view]

PRINTS

PR00081. GDHRDH.
PR00080. SDRFAMILY.

PROSITE

PS00061. ADH_SHORT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL6008.

EvolutionaryTrace

O75828.

GenomeRNAi

874.

NextBio

3638.

SOURCE

Search...

Entry information

Entry name

CBR3_HUMAN

Accession

Primary (citable) accession number: O75828
Secondary accession number(s): Q6FHP2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 118 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.