DB code: S00331

RLCP classification 9.5010.536200.8010 : Hydride transfer
CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
E.C. 1.1.1.184
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.720 : Rossmann fold S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 S00610 S00625 S00319 S00328 S00329 S00330 S00332 D00456 D00457 D00458 S00324 S00320 S00325 S00326 S00327 D00459 S00335 S00336 S00334 T00219 S00339 D00513 D00001 D00002 D00003 D00005 D00007 D00008 D00010 D00012 D00017 D00018 D00023 D00027 D00028 D00031 D00032 D00033 D00034 D00035 D00037 D00048 D00071 D00476 D00481 D00482 D00490 D00492 D00494 D00545 D00601 D00603 D00604 D00605 D00615 D00845 D00857 D00858 M00161 M00171 M00210 T00002 T00010 T00011 T00015 T00227 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q9W3H4
Sniffer
EC 1.1.1.184
LD36273p
NP_572466.1 (Protein)
NM_132238.3 (DNA/RNA sequence)
PF00106 (adh_short)
[Graphical View]
P08074 Carbonyl reductase {NADPH} 2
EC 1.1.1.184
NADPH-dependent carbonyl reductase 2
Lung carbonyl reductase
LCR
Adipocyte protein P27
AP27
NP_031647.1 (Protein)
NM_007621.2 (DNA/RNA sequence)
PF00106 (adh_short)
[Graphical View]
Q8WNV7 Dehydrogenase/reductase SDR family member 4
EC 1.1.1.184
NADPH-dependent carbonyl reductase/NADP-retinol dehydrogenase
PHCR
CR
Peroxisomal short-chain alcohol dehydrogenase
NADPH-dependent retinol dehydrogenase/reductase
NDRD
NP_999184.1 (Protein)
NM_214019.1 (DNA/RNA sequence)
[Graphical View]
Q9BTZ2 Dehydrogenase/reductase SDR family member 4
EC 1.1.1.184
Short-chain dehydrogenase/reductase family member 4
NADPH-dependent carbonyl reductase/NADP-retinol dehydrogenase
PHCR
CR
Peroxisomal short-chain alcohol dehydrogenase
PSCD
NADPH-dependent retinol dehydrogenase/reductase
NRDR
humNRDR
SCAD-SRL
NP_066284.2 (Protein)
NM_021004.2 (DNA/RNA sequence)
[Graphical View]
O75828 Carbonyl reductase {NADPH} 3
EC 1.1.1.184
NADPH-dependent carbonyl reductase 3
NP_001227.1 (Protein)
NM_001236.3 (DNA/RNA sequence)
PF00106 (adh_short)
[Graphical View]

KEGG enzyme name
carbonyl reductase (NADPH)
aldehyde reductase 1
prostaglandin 9-ketoreductase
xenobiotic ketone reductase
NADPH-dependent carbonyl reductase
ALR3
carbonyl reductase
nonspecific NADPH-dependent carbonyl reductase
aldehyde reductase 1
carbonyl reductase (NADPH)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9W3H4 Q9W3H4_DROME
P08074 CBR2_MOUSE R-CHOH-R' + NADP(+) = R-CO-R' + NADPH. Homotetramer. Mitochondrion matrix.
Q8WNV7 DHRS4_PIG R-CHOH-R' + NADP(+) = R-CO-R' + NADPH. Homotetramer. Peroxisome.
Q9BTZ2 DHRS4_HUMAN R-CHOH-R' + NADP(+) = R-CO-R' + NADPH. Homotetramer (By similarity). Peroxisome. Note=Isoform 1 is peroxisomal, while isoform 4 is not.
O75828 CBR3_HUMAN R-CHOH-R' + NADP(+) = R-CO-R' + NADPH. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00590 Arachidonic acid metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00005 C01450 C00080 C00006 C01612
E.C.
Compound NADPH R-CO-R' H+ NADP+ R-CHOH-R'
Type amide group,amine group,nucleotide carbohydrate others amide group,amine group,nucleotide carbohydrate
ChEBI 16474
15378
18009
PubChem 5884
1038
5886
1snyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
1cydA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Bound:IPA
1cydB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Bound:IPA
1cydC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Bound:IPA
1cydD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Bound:IPA
2zatA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
2zatB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
2zatC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
2zatD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
3o4rA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
3o4rB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Bound:GOL
3o4rC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Bound:GOL
3o4rD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound
2hrbA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NAP Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P08074 & literature [10]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1snyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 154;TYR 170;LYS 174
1cydA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 136;TYR 149;LYS 153
1cydB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 136;TYR 149;LYS 153
1cydC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 136;TYR 149;LYS 153
1cydD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 136;TYR 149;LYS 153
2zatA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 151;TYR 164;LYS 168
2zatB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 151;TYR 164;LYS 168
2zatC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 151;TYR 164;LYS 168
2zatD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 151;TYR 164;LYS 168
3o4rA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 169;TYR 182;LYS 186
3o4rB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 169;TYR 182;LYS 186
3o4rC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 169;TYR 182;LYS 186
3o4rD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 169;TYR 182;LYS 186
2hrbA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 140;TYR 194;LYS 198

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[10]
p.42
[12]
p.559-560
[17]
p.1617
[18]
p.392

References
[1]
Resource
Comments
Medline ID
PubMed ID 3511844
Journal Arch Biochem Biophys
Year 1986
Volume 244
Pages 238-47
Authors Hara A, Nakayama T, Deyashiki Y, Kariya K, Sawada H
Title Carbonyl reductase of dog liver: purification, properties, and kinetic mechanism.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2388711
Journal Neurochem Res
Year 1990
Volume 15
Pages 385-92
Authors Hayashi H, Fujii Y, Watanabe K, Hayaishi O
Title Enzymatic formation of prostaglandin F2 alpha in human brain.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 1449827
Journal Eicosanoids
Year 1992
Volume 5 Suppl
Pages S37-8
Authors Schieber A, Ghisla S
Title Prostaglandin 9-ketoreductase from pig and human kidney: purification, properties and identity with human carbonyl reductase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1576998
Journal Eur J Biochem
Year 1992
Volume 205
Pages 1155-62
Authors Klein J, Thomas H, Post K, Worner W, Oesch F
Title Dihydrodiol dehydrogenase activities of rabbit liver are associated with hydroxysteroid dehydrogenases and aldo-keto reductases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 1597188
Journal Eur J Biochem
Year 1992
Volume 206
Pages 491-502
Authors Schieber A, Frank RW, Ghisla S
Title Purification and properties of prostaglandin 9-ketoreductase from pig and human kidney. Identity with human carbonyl reductase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8421682
Journal Proc Natl Acad Sci U S A
Year 1993
Volume 90
Pages 502-6
Authors Krook M, Ghosh D, Stromberg R, Carlquist M, Jornvall H
Title Carboxyethyllysine in a protein: native carbonyl reductase/NADP(+)-dependent prostaglandin dehydrogenase.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 7990149
Journal J Mol Biol
Year 1994
Volume 244
Pages 659-64
Authors Bohren KM, Wermuth B, Harrison D, Ringe D, Petsko GA, Gabbay KH
Title Expression, crystallization and preliminary crystallographic analysis of human carbonyl reductase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 7981120
Journal J Steroid Biochem Mol Biol
Year 1994
Volume 51
Pages 125-30
Authors Krozowski Z
Title The short-chain alcohol dehydrogenase superfamily: variations on a common theme.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8889808
Journal J Biochem (Tokyo)
Year 1996
Volume 120
Pages 257-63
Authors Nakanishi M, Kakumoto M, Matsuura K, Deyashiki Y, Tanaka N, Nonaka T, Mitsui Y, Hara A
Title Involvement of two basic residues (Lys-17 and Arg-39) of mouse lung carbonyl reductase in NADP(H)-binding and fatty acid activation: site-directed mutagenesis and kinetic analyses.
Related PDB
Related UniProtKB
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH NADPH.
Medline ID
PubMed ID 8805511
Journal Structure
Year 1996
Volume 4
Pages 33-45
Authors Tanaka N, Nonaka T, Nakanishi M, Deyashiki Y, Hara A, Mitsui Y
Title Crystal structure of the ternary complex of mouse lung carbonyl reductase at 1.8 A resolution: the structural origin of coenzyme specificity in the short-chain dehydrogenase/reductase family.
Related PDB 1cyd
Related UniProtKB P08074
[11]
Resource
Comments
Medline ID
PubMed ID 9059665
Journal Adv Exp Med Biol
Year 1997
Volume 414
Pages 579-600
Authors Jez JM, Flynn TG, Penning TM
Title A nomenclature system for the aldo-keto reductase superfamily.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 9059662
Journal Adv Exp Med Biol
Year 1997
Volume 414
Pages 555-61
Authors Nakanishi M, Kaibe H, Matsuura K, Kakumoto M, Tanaka N, Nonaka T, Mitsui Y, Hara A
Title Site-directed mutagenesis of residues in coenzyme-binding domain and active site of mouse lung carbonyl reductase.
Related PDB
Related UniProtKB
[13]
Resource
Comments MUTAGENESIS OF THR-38, AND COENZYME SPECIFICITY.
Medline ID
PubMed ID 8999926
Journal J Biol Chem
Year 1997
Volume 272
Pages 2218-22
Authors Nakanishi M, Matsuura K, Kaibe H, Tanaka N, Nonaka T, Mitsui Y, Hara A
Title Switch of coenzyme specificity of mouse lung carbonyl reductase by substitution of threonine 38 with aspartic acid.
Related PDB
Related UniProtKB P08074
[14]
Resource
Comments
Medline ID
PubMed ID 9729461
Journal Biochem J
Year 1998
Volume 334
Pages 553-7
Authors Nakajin S, Takase N, Ohno S, Toyoshima S, Baker ME
Title Mutation of tyrosine-194 and lysine-198 in the catalytic site of pig 3alpha/beta,20beta-hydroxysteroid dehydrogenase.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9880795
Journal J Biochem (Tokyo)
Year 1999
Volume 125
Pages 41-7
Authors Imamura Y, Migita T, Otagiri M, Choshi T, Hibino S
Title Purification and catalytic properties of a tetrameric carbonyl reductase from rabbit heart.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 11279087
Journal J Biol Chem
Year 2001
Volume 276
Pages 18457-63
Authors Ghosh D, Sawicki M, Pletnev V, Erman M, Ohno S, Nakajin S, Duax WL
Title Porcine carbonyl reductase. structural basis for a functional monomer in short chain dehydrogenases/reductases.
Related PDB 1hu4 1n5d
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 15364585
Journal J Mol Biol
Year 2004
Volume 342
Pages 1613-24
Authors Sgraja T, Ulschmid J, Becker K, Schneuwly S, Klebe G, Reuter K, Heine A
Title Structural insights into the neuroprotective-acting carbonyl reductase Sniffer of Drosophila melanogaster.
Related PDB 1sny
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 18334214
Journal Structure
Year 2008
Volume 16
Pages 388-97
Authors Tanaka N, Aoki K, Ishikura S, Nagano M, Imamura Y, Hara A, Nakamura KT
Title Molecular basis for peroxisomal localization of tetrameric carbonyl reductase.
Related PDB 2zat
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 19056333
Journal Arch Biochem Biophys
Year 2009
Volume 481
Pages 183-90
Authors Endo S, Maeda S, Matsunaga T, Dhagat U, El-Kabbani O, Tanaka N, Nakamura KT, Tajima K, Hara A
Title Molecular determinants for the stereospecific reduction of 3-ketosteroids and reactivity towards all-trans-retinal of a short-chain dehydrogenase/reductase (DHRS4).
Related PDB
Related UniProtKB

Comments
This enzyme belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, along with Drosophia alcohol dehydrogenase (S00319 in EzCatDB). This enzyme has got a catalytic triad composed of conserved residues, Ser, Tyr, and Lys. The conformation of these residues, compared to that of the NADP+ molecule, seems to be similar to those of the homologous enzymes.
This enzyme seems to catalyze the reduction of a variety of carbonyl compounds.

Created Updated
2005-01-24 2011-06-30