Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Aldo-keto reductase family 1 member C3

Gene

AKR1C3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.

Catalytic activityi

Trans-1,2-dihydrobenzene-1,2-diol + NADP+ = catechol + NADPH.
A 3-alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H.
(5Z,13E)-(15S)-9-alpha,11-alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ = (5Z,13E)-(15S)-9-alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH.
Testosterone + NAD+ = androstenedione + NADH.
Testosterone + NADP+ = androst-4-ene-3,17-dione + NADPH.
Indan-1-ol + NAD(P)+ = indanone + NAD(P)H.

Enzyme regulationi

Strongly inhibited by nonsteroidal anti-inflammatory drugs (NSAID) including flufenamic acid and indomethacin. Also inhibited by the flavinoid, rutin, and by selective serotonin inhibitors (SSRIs).

Kineticsi

  1. KM=142.1 µM for progesterone1 Publication
  2. KM=2.37 µM for 5-alpha-dihydrotestosterone1 Publication
  3. KM=1.0 µM for androstanediol1 Publication
  1. Vmax=20.1 nmol/min/mg enzyme with progesterone as substrate1 Publication
  2. Vmax=1.8 nmol/min/mg enzyme with 5-alpha-dihydrotestosterone as substrate1 Publication
  3. Vmax=4.4 nmol/min/mg enzyme with androstanediol as substrate1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei54 – 541Important for substrate specificityBy similarity
Active sitei55 – 551Proton donorBy similarity
Sitei84 – 841Lowers pKa of active site TyrBy similarity
Binding sitei117 – 1171SubstrateBy similarity
Sitei227 – 2271Involved in ligand recognition and product release
Sitei306 – 3061Involved in ligand recognition and product release

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi13 – 2210NADPSequence Analysis
Nucleotide bindingi217 – 28064NADPBy similarityAdd
BLAST

GO - Molecular functioni

  • 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity Source: UniProtKB
  • alditol:NADP+ 1-oxidoreductase activity Source: UniProtKB
  • aldo-keto reductase (NADP) activity Source: UniProtKB
  • androsterone dehydrogenase activity Source: UniProtKB
  • delta4-3-oxosteroid 5beta-reductase activity Source: UniProtKB
  • dihydrotestosterone 17-beta-dehydrogenase activity Source: UniProtKB
  • geranylgeranyl reductase activity Source: UniProtKB
  • indanol dehydrogenase activity Source: UniProtKB-EC
  • ketoreductase activity Source: UniProtKB
  • ketosteroid monooxygenase activity Source: UniProtKB
  • oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor Source: UniProtKB
  • phenanthrene 9,10-monooxygenase activity Source: UniProtKB
  • prostaglandin D2 11-ketoreductase activity Source: UniProtKB-EC
  • prostaglandin-F synthase activity Source: UniProtKB-EC
  • retinal dehydrogenase activity Source: UniProtKB
  • retinol dehydrogenase activity Source: UniProtKB
  • testosterone 17-beta-dehydrogenase (NADP+) activity Source: UniProtKB-EC
  • testosterone dehydrogenase (NAD+) activity Source: UniProtKB-EC
  • trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity Source: UniProtKB-EC

GO - Biological processi

  • arachidonic acid metabolic process Source: Reactome
  • cellular response to cadmium ion Source: UniProtKB
  • cellular response to calcium ion Source: UniProtKB
  • cellular response to corticosteroid stimulus Source: UniProtKB
  • cellular response to jasmonic acid stimulus Source: UniProtKB
  • cellular response to prostaglandin D stimulus Source: UniProtKB
  • cellular response to prostaglandin stimulus Source: UniProtKB
  • cellular response to reactive oxygen species Source: UniProtKB
  • cellular response to starvation Source: UniProtKB
  • cyclooxygenase pathway Source: Reactome
  • daunorubicin metabolic process Source: UniProtKB
  • doxorubicin metabolic process Source: UniProtKB
  • farnesol catabolic process Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • keratinocyte differentiation Source: UniProtKB
  • male gonad development Source: UniProtKB
  • multicellular organismal macromolecule metabolic process Source: UniProtKB
  • negative regulation of retinoic acid biosynthetic process Source: UniProtKB
  • oxidation-reduction process Source: UniProtKB
  • phototransduction, visible light Source: Reactome
  • positive regulation of cell death Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of endothelial cell apoptotic process Source: UniProtKB
  • positive regulation of protein kinase B signaling Source: UniProtKB
  • positive regulation of reactive oxygen species metabolic process Source: UniProtKB
  • progesterone metabolic process Source: UniProtKB
  • prostaglandin metabolic process Source: UniProtKB
  • protein import into nucleus, translocation Source: UniProtKB
  • regulation of retinoic acid receptor signaling pathway Source: UniProtKB
  • regulation of testosterone biosynthetic process Source: UniProtKB
  • renal absorption Source: UniProtKB
  • response to nutrient Source: UniProtKB
  • retinal metabolic process Source: UniProtKB
  • retinoid metabolic process Source: Reactome
  • small molecule metabolic process Source: Reactome
  • steroid metabolic process Source: UniProtKB
  • testosterone biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

NAD, NADP

Enzyme and pathway databases

BRENDAi1.1.1.188. 2681.
1.1.1.21. 2681.
1.1.1.213. 2681.
1.1.1.239. 2681.
1.1.1.357. 2681.
1.1.1.64. 2681.
1.3.1.20. 2681.
ReactomeiREACT_11041. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
REACT_11048. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
REACT_11053. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
REACT_150149. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
REACT_24968. Retinoid metabolism and transport.
REACT_268561. RA biosynthesis pathway.
SABIO-RKP42330.

Names & Taxonomyi

Protein namesi
Recommended name:
Aldo-keto reductase family 1 member C3 (EC:1.-.-.-)
Alternative name(s):
17-beta-hydroxysteroid dehydrogenase type 5
Short name:
17-beta-HSD 5
3-alpha-HSD type II, brain
3-alpha-hydroxysteroid dehydrogenase type 2 (EC:1.1.1.357)
Short name:
3-alpha-HSD type 2
Chlordecone reductase homolog HAKRb
Dihydrodiol dehydrogenase 3
Short name:
DD-3
Short name:
DD3
Dihydrodiol dehydrogenase type I
HA1753
Indanol dehydrogenase (EC:1.1.1.112)
Prostaglandin F synthase (EC:1.1.1.188)
Short name:
PGFS
Testosterone 17-beta-dehydrogenase 5 (EC:1.1.1.239, EC:1.1.1.64)
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase (EC:1.3.1.20)
Gene namesi
Name:AKR1C3
Synonyms:DDH1, HSD17B5, KIAA0119, PGFS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:386. AKR1C3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • intracellular Source: LIFEdb
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi75 – 751K → E: No effect on 17beta-HSD activity. 1 Publication

Organism-specific databases

PharmGKBiPA24679.

Chemistry

DrugBankiDB00905. Bimatoprost.
DB00997. Doxorubicin.

Polymorphism and mutation databases

BioMutaiAKR1C3.
DMDMi308153646.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 323323Aldo-keto reductase family 1 member C3PRO_0000124638Add
BLAST

Proteomic databases

MaxQBiP42330.
PaxDbiP42330.
PRIDEiP42330.

2D gel databases

DOSAC-COBS-2DPAGEP42330.

PTM databases

PhosphoSiteiP42330.

Expressioni

Tissue specificityi

Expressed in many tissues including adrenal gland, brain, kidney, liver, lung, mammary gland, placenta, small intestine, colon, spleen, prostate and testis. The dominant HSD in prostate and mammary gland. In the prostate, higher levels in epithelial cells than in stromal cells. In the brain, expressed in medulla, spinal cord, frontotemporal lobes, thalamus, subthalamic nuclei and amygdala. Weaker expression in the hippocampus, substantia nigra and caudate.6 Publications

Gene expression databases

BgeeiP42330.
CleanExiHS_AKR1C3.
ExpressionAtlasiP42330. baseline and differential.
GenevisibleiP42330. HS.

Organism-specific databases

HPAiCAB010874.

Interactioni

Protein-protein interaction databases

BioGridi114196. 9 interactions.
IntActiP42330. 5 interactions.
MINTiMINT-1379107.

Structurei

Secondary structure

1
323
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi7 – 93Combined sources
Beta strandi15 – 228Combined sources
Helixi33 – 4412Combined sources
Beta strandi48 – 503Combined sources
Helixi53 – 553Combined sources
Helixi58 – 7013Combined sources
Helixi76 – 783Combined sources
Beta strandi80 – 856Combined sources
Helixi87 – 893Combined sources
Helixi92 – 943Combined sources
Helixi95 – 10612Combined sources
Beta strandi111 – 1166Combined sources
Beta strandi124 – 1263Combined sources
Beta strandi133 – 1353Combined sources
Helixi144 – 15613Combined sources
Beta strandi159 – 1679Combined sources
Helixi170 – 1778Combined sources
Beta strandi187 – 1926Combined sources
Helixi200 – 2089Combined sources
Beta strandi212 – 2176Combined sources
Turni225 – 2273Combined sources
Helixi235 – 2373Combined sources
Helixi239 – 24810Combined sources
Helixi252 – 26211Combined sources
Beta strandi266 – 2705Combined sources
Helixi274 – 2807Combined sources
Helixi281 – 2855Combined sources
Helixi290 – 2978Combined sources
Helixi309 – 3124Combined sources
Helixi318 – 3203Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RY0X-ray1.69A/B1-323[»]
1RY8X-ray1.69A/B1-323[»]
1S1PX-ray1.20A1-323[»]
1S1RX-ray2.00A1-323[»]
1S2AX-ray1.70A1-323[»]
1S2CX-ray1.80A1-323[»]
1XF0X-ray2.00A1-323[»]
1ZQ5X-ray1.30A1-323[»]
2F38X-ray2.00A1-323[»]
2FGBX-ray1.35A1-323[»]
3R43X-ray2.00A1-323[»]
3R58X-ray2.30A1-323[»]
3R6IX-ray1.95A1-323[»]
3R7MX-ray2.10A1-323[»]
3R8GX-ray1.80A1-323[»]
3R8HX-ray1.90A1-323[»]
3R94X-ray2.01A1-323[»]
3UFYX-ray1.90A1-323[»]
3UG8X-ray1.73A1-323[»]
3UGRX-ray1.65A1-323[»]
3UWEX-ray1.68A1-323[»]
4DBSX-ray1.85A/B1-323[»]
4DBUX-ray2.53A/B1-323[»]
4DBWX-ray1.80A/B1-323[»]
4DZ5X-ray1.70A1-323[»]
4FA3X-ray2.20A1-323[»]
4FALX-ray2.00A1-323[»]
4FAMX-ray2.00A/B1-323[»]
4H7CX-ray1.97A1-323[»]
4HMNX-ray2.40A1-323[»]
4WDTX-ray1.50A1-323[»]
4WDUX-ray1.70A1-323[»]
4WDWX-ray1.94A/B1-323[»]
4WDXX-ray1.64A/B1-323[»]
4WRHX-ray1.60A1-323[»]
4XVDX-ray2.81A/B1-323[»]
4XVEX-ray1.55A1-323[»]
ProteinModelPortaliP42330.
SMRiP42330. Positions 6-320.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42330.

Family & Domainsi

Sequence similaritiesi

Belongs to the aldo/keto reductase family.Curated

Phylogenomic databases

eggNOGiCOG0656.
GeneTreeiENSGT00760000119041.
HOVERGENiHBG000020.
InParanoidiP42330.
KOiK04119.
OMAiIPWCEAH.
OrthoDBiEOG70KGQF.
PhylomeDBiP42330.
TreeFamiTF106492.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR001395. Aldo/ket_red.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase_subgr.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR11732. PTHR11732. 1 hit.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
PIRSFiPIRSF000097. AKR. 1 hit.
PRINTSiPR00069. ALDKETRDTASE.
SUPFAMiSSF51430. SSF51430. 1 hit.
PROSITEiPS00798. ALDOKETO_REDUCTASE_1. 1 hit.
PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P42330-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDSKHQCVKL NDGHFMPVLG FGTYAPPEVP RSKALEVTKL AIEAGFRHID
60 70 80 90 100
SAHLYNNEEQ VGLAIRSKIA DGSVKREDIF YTSKLWSTFH RPELVRPALE
110 120 130 140 150
NSLKKAQLDY VDLYLIHSPM SLKPGEELSP TDENGKVIFD IVDLCTTWEA
160 170 180 190 200
MEKCKDAGLA KSIGVSNFNR RQLEMILNKP GLKYKPVCNQ VECHPYFNRS
210 220 230 240 250
KLLDFCKSKD IVLVAYSALG SQRDKRWVDP NSPVLLEDPV LCALAKKHKR
260 270 280 290 300
TPALIALRYQ LQRGVVVLAK SYNEQRIRQN VQVFEFQLTA EDMKAIDGLD
310 320
RNLHYFNSDS FASHPNYPYS DEY
Length:323
Mass (Da):36,853
Last modified:October 5, 2010 - v4
Checksum:i86A7690D9498C6FD
GO
Isoform 2 (identifier: P42330-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-119: Missing.

Note: No experimental confirmation available.
Show »
Length:204
Mass (Da):23,364
Checksum:i02F3AC7C2BB5BF78
GO

Sequence cautioni

The sequence BAA04619.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 31S → P no nucleotide entry (PubMed:7626489).Curated
Sequence conflicti6 – 61Q → K no nucleotide entry (PubMed:7626489).Curated
Sequence conflicti38 – 381T → S in AAF07272 (PubMed:10557352).Curated
Sequence conflicti75 – 751K → E in AAD14011 (PubMed:8274401).Curated
Sequence conflicti75 – 751K → E no nucleotide entry (PubMed:7626489).Curated
Sequence conflicti75 – 751K → M in AAB41916 (PubMed:7650035).Curated
Sequence conflicti89 – 891F → S in AAF07272 (PubMed:10557352).Curated
Sequence conflicti270 – 2701K → R in AAF07272 (PubMed:10557352).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti5 – 51H → Q.7 Publications
Corresponds to variant rs12529 [ dbSNP | Ensembl ].
VAR_013288
Natural varianti66 – 661R → Q.
Corresponds to variant rs35961894 [ dbSNP | Ensembl ].
VAR_032767
Natural varianti77 – 771E → G.
Corresponds to variant rs41306308 [ dbSNP | Ensembl ].
VAR_061001
Natural varianti170 – 1701R → C.
Corresponds to variant rs35575889 [ dbSNP | Ensembl ].
VAR_032768
Natural varianti175 – 1751M → I No effect on 17beta-HSD activity. 3 Publications
Corresponds to variant rs1131132 [ dbSNP | Ensembl ].
VAR_013289
Natural varianti180 – 1801P → S.
Corresponds to variant rs34186955 [ dbSNP | Ensembl ].
VAR_032769

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 119119Missing in isoform 2. 1 PublicationVSP_055798Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S68288 mRNA. Translation: AAD14011.1.
L43839
, L43831, L43832, L43833, L43834, L43835, L43836, L43837, L43838 Genomic DNA. Translation: AAB41916.1.
AB018580 mRNA. Translation: BAA88488.1.
AB028065 Genomic DNA. Translation: BAA88489.1.
AF149416 mRNA. Translation: AAF07272.2.
AB032157 Genomic DNA. Translation: BAA92892.1.
D17793 mRNA. Translation: BAA04619.2. Different initiation.
BT007286 mRNA. Translation: AAP35950.1.
AK290365 mRNA. Translation: BAF83054.1.
AK296829 mRNA. Translation: BAG59399.1.
AL391427 Genomic DNA. No translation available.
CH471072 Genomic DNA. Translation: EAW86454.1.
BC001479 mRNA. Translation: AAH01479.1.
BC019230 mRNA. Translation: AAH19230.1.
CCDSiCCDS7063.1. [P42330-1]
PIRiB57407.
I73674.
RefSeqiNP_001240837.1. NM_001253908.1.
NP_003730.4. NM_003739.5. [P42330-1]
UniGeneiHs.78183.

Genome annotation databases

EnsembliENST00000380554; ENSP00000369927; ENSG00000196139. [P42330-1]
GeneIDi8644.
KEGGihsa:8644.
UCSCiuc001ihr.3. human. [P42330-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S68288 mRNA. Translation: AAD14011.1.
L43839
, L43831, L43832, L43833, L43834, L43835, L43836, L43837, L43838 Genomic DNA. Translation: AAB41916.1.
AB018580 mRNA. Translation: BAA88488.1.
AB028065 Genomic DNA. Translation: BAA88489.1.
AF149416 mRNA. Translation: AAF07272.2.
AB032157 Genomic DNA. Translation: BAA92892.1.
D17793 mRNA. Translation: BAA04619.2. Different initiation.
BT007286 mRNA. Translation: AAP35950.1.
AK290365 mRNA. Translation: BAF83054.1.
AK296829 mRNA. Translation: BAG59399.1.
AL391427 Genomic DNA. No translation available.
CH471072 Genomic DNA. Translation: EAW86454.1.
BC001479 mRNA. Translation: AAH01479.1.
BC019230 mRNA. Translation: AAH19230.1.
CCDSiCCDS7063.1. [P42330-1]
PIRiB57407.
I73674.
RefSeqiNP_001240837.1. NM_001253908.1.
NP_003730.4. NM_003739.5. [P42330-1]
UniGeneiHs.78183.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RY0X-ray1.69A/B1-323[»]
1RY8X-ray1.69A/B1-323[»]
1S1PX-ray1.20A1-323[»]
1S1RX-ray2.00A1-323[»]
1S2AX-ray1.70A1-323[»]
1S2CX-ray1.80A1-323[»]
1XF0X-ray2.00A1-323[»]
1ZQ5X-ray1.30A1-323[»]
2F38X-ray2.00A1-323[»]
2FGBX-ray1.35A1-323[»]
3R43X-ray2.00A1-323[»]
3R58X-ray2.30A1-323[»]
3R6IX-ray1.95A1-323[»]
3R7MX-ray2.10A1-323[»]
3R8GX-ray1.80A1-323[»]
3R8HX-ray1.90A1-323[»]
3R94X-ray2.01A1-323[»]
3UFYX-ray1.90A1-323[»]
3UG8X-ray1.73A1-323[»]
3UGRX-ray1.65A1-323[»]
3UWEX-ray1.68A1-323[»]
4DBSX-ray1.85A/B1-323[»]
4DBUX-ray2.53A/B1-323[»]
4DBWX-ray1.80A/B1-323[»]
4DZ5X-ray1.70A1-323[»]
4FA3X-ray2.20A1-323[»]
4FALX-ray2.00A1-323[»]
4FAMX-ray2.00A/B1-323[»]
4H7CX-ray1.97A1-323[»]
4HMNX-ray2.40A1-323[»]
4WDTX-ray1.50A1-323[»]
4WDUX-ray1.70A1-323[»]
4WDWX-ray1.94A/B1-323[»]
4WDXX-ray1.64A/B1-323[»]
4WRHX-ray1.60A1-323[»]
4XVDX-ray2.81A/B1-323[»]
4XVEX-ray1.55A1-323[»]
ProteinModelPortaliP42330.
SMRiP42330. Positions 6-320.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114196. 9 interactions.
IntActiP42330. 5 interactions.
MINTiMINT-1379107.

Chemistry

BindingDBiP42330.
ChEMBLiCHEMBL4681.
DrugBankiDB00905. Bimatoprost.
DB00997. Doxorubicin.

PTM databases

PhosphoSiteiP42330.

Polymorphism and mutation databases

BioMutaiAKR1C3.
DMDMi308153646.

2D gel databases

DOSAC-COBS-2DPAGEP42330.

Proteomic databases

MaxQBiP42330.
PaxDbiP42330.
PRIDEiP42330.

Protocols and materials databases

DNASUi8644.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380554; ENSP00000369927; ENSG00000196139. [P42330-1]
GeneIDi8644.
KEGGihsa:8644.
UCSCiuc001ihr.3. human. [P42330-1]

Organism-specific databases

CTDi8644.
GeneCardsiGC10P005077.
HGNCiHGNC:386. AKR1C3.
HPAiCAB010874.
MIMi603966. gene.
neXtProtiNX_P42330.
PharmGKBiPA24679.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0656.
GeneTreeiENSGT00760000119041.
HOVERGENiHBG000020.
InParanoidiP42330.
KOiK04119.
OMAiIPWCEAH.
OrthoDBiEOG70KGQF.
PhylomeDBiP42330.
TreeFamiTF106492.

Enzyme and pathway databases

BRENDAi1.1.1.188. 2681.
1.1.1.21. 2681.
1.1.1.213. 2681.
1.1.1.239. 2681.
1.1.1.357. 2681.
1.1.1.64. 2681.
1.3.1.20. 2681.
ReactomeiREACT_11041. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
REACT_11048. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
REACT_11053. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
REACT_150149. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
REACT_24968. Retinoid metabolism and transport.
REACT_268561. RA biosynthesis pathway.
SABIO-RKP42330.

Miscellaneous databases

ChiTaRSiAKR1C3. human.
EvolutionaryTraceiP42330.
GeneWikiiAKR1C3.
GenomeRNAii8644.
NextBioi32407.
PROiP42330.
SOURCEiSearch...

Gene expression databases

BgeeiP42330.
CleanExiHS_AKR1C3.
ExpressionAtlasiP42330. baseline and differential.
GenevisibleiP42330. HS.

Family and domain databases

Gene3Di3.20.20.100. 1 hit.
InterProiIPR001395. Aldo/ket_red.
IPR018170. Aldo/ket_reductase_CS.
IPR020471. Aldo/keto_reductase_subgr.
IPR023210. NADP_OxRdtase_dom.
[Graphical view]
PANTHERiPTHR11732. PTHR11732. 1 hit.
PfamiPF00248. Aldo_ket_red. 1 hit.
[Graphical view]
PIRSFiPIRSF000097. AKR. 1 hit.
PRINTSiPR00069. ALDKETRDTASE.
SUPFAMiSSF51430. SSF51430. 1 hit.
PROSITEiPS00798. ALDOKETO_REDUCTASE_1. 1 hit.
PS00062. ALDOKETO_REDUCTASE_2. 1 hit.
PS00063. ALDOKETO_REDUCTASE_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase."
    Qin K.-N., New M.I., Cheng K.-C.
    J. Steroid Biochem. Mol. Biol. 46:673-679(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GLN-5 AND ILE-175.
    Tissue: Liver.
  2. "Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases."
    Khanna M., Qin K.-N., Wang R.W., Cheng K.-C.
    J. Biol. Chem. 270:20162-20168(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION, TISSUE SPECIFICITY, VARIANTS GLN-5 AND ILE-175.
  3. "Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans."
    Khanna M., Qin K.-N., Cheng K.-C.
    J. Steroid Biochem. Mol. Biol. 53:41-46(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLN-5.
    Tissue: Liver.
  4. "Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution."
    Lin H.-K., Jez J.M., Schlegel B.P., Peehl D.M., Pachter J.A., Penning T.M.
    Mol. Endocrinol. 11:1971-1984(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, TISSUE SPECIFICITY, VARIANT GLN-5.
    Tissue: Prostate.
  5. "cDNA cloning, expression and characterization of human prostaglandin F synthase."
    Suzuki-Yamamoto T., Nishizawa M., Fukui M., Okuda-Ashitaka E., Nakajima T., Ito S., Watanabe K.
    FEBS Lett. 462:335-340(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 124-190, CHARACTERIZATION, TISSUE SPECIFICITY, VARIANT GLN-5.
    Tissue: Lung.
  6. "Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes."
    Griffin L.D., Mellon S.H.
    Proc. Natl. Acad. Sci. U.S.A. 96:13512-13517(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, VARIANT GLN-5.
    Tissue: Brain.
  7. "Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes."
    Nishizawa M., Nakajima T., Yasuda K., Kanzaki H., Sasaguri Y., Watanabe K., Ito S.
    Genes Cells 5:111-125(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Liver.
  8. "Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3)."
    Penning T.M., Burczynski M.E., Jez J.M., Lin H.-K., Ma H., Moore M., Ratnam K., Palackal N.
    Mol. Cell. Endocrinol. 171:137-149(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, TISSUE SPECIFICITY.
    Tissue: Prostate.
  9. "Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1."
    Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.
    DNA Res. 2:37-43(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLN-5.
    Tissue: Bone marrow.
  10. "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 (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  11. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Tongue.
  12. "The DNA sequence and comparative analysis of human chromosome 10."
    Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
    , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
    Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  13. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  14. "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] (ISOFORM 1).
    Tissue: Colon and Urinary bladder.
  15. "Characteristics of a highly labile human type 5 17beta-hydroxysteroid dehydrogenase."
    Dufort I., Rheault P., Huang X.-F., Soucy P., Luu-The V.
    Endocrinology 140:568-574(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION, TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT ILE-175, MUTAGENESIS OF LYS-75.
  16. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  17. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  18. "Crystal structure of human prostaglandin F synthase (AKR1C3)."
    Komoto J., Yamada T., Watanabe K., Takusagawa F.
    Biochemistry 43:2188-2198(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH PROSTAGLANDIN H(2); NADPH AND RUTIN.
  19. "Crystal structures of prostaglandin D(2) 11-ketoreductase (AKR1C3) in complex with the nonsteroidal anti-inflammatory drugs flufenamic acid and indomethacin."
    Lovering A.L., Ride J.P., Bunce C.M., Desmond J.C., Cummings S.M., White S.A.
    Cancer Res. 64:1802-1810(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH FLUFENAMIC ACID AND INDOMETHACIN.
  20. "Crystal structures of the multispecific 17beta-hydroxysteroid dehydrogenase type 5: critical androgen regulation in human peripheral tissues."
    Qiu W., Zhou M., Labrie F., Lin S.-X.
    Mol. Endocrinol. 18:1798-1807(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH NADP AND DELTA4 -3 ANDROSTENE-3,17-DIONE, IMPORTANCE OF TRP-227 AND PHE-306 IN LIGAND RECOGNITION AND PRODUCT RELEASE.

Entry informationi

Entry nameiAK1C3_HUMAN
AccessioniPrimary (citable) accession number: P42330
Secondary accession number(s): A8K2V0
, B4DL37, Q5T2L1, Q96DJ1, Q96KI8, Q99530, Q9UCX1, Q9UII3, Q9UKL9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: October 5, 2010
Last modified: June 24, 2015
This is version 168 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.