Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003634
UniProt IDP42330
Primary gene name(s)AKR1C3
Synonym gene name(s)DDH1, HSD17B5, KIAA0119, PGFS
Protein nameAldo-keto reductase family 1 member C3
Protein functionCatalyzes 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.
Subcellular locationCytoplasm.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P42330
Gene Ontology
(Biological Process)
Complete annatation
cellular response to cadmium ion [GO:0071276];
cellular response to calcium ion [GO:0071277];
cellular response to corticosteroid stimulus [GO:0071384];
cellular response to jasmonic acid stimulus [GO:0071395];
cellular response to prostaglandin D stimulus [GO:0071799];
cellular response to prostaglandin stimulus [GO:0071379];
cellular response to reactive oxygen species [GO:0034614];
cellular response to starvation [GO:0009267];
cyclooxygenase pathway [GO:0019371];
daunorubicin metabolic process [GO:0044597];
doxorubicin metabolic process [GO:0044598];
farnesol catabolic process [GO:0016488];
G-protein coupled receptor signaling pathway [GO:0007186];
keratinocyte differentiation [GO:0030216];
male gonad development [GO:0008584];
multicellular organismal macromolecule metabolic process [GO:0044259];
negative regulation of retinoic acid biosynthetic process [GO:1900053];
oxidation-reduction process [GO:0055114];
positive regulation of cell death [GO:0010942];
positive regulation of cell proliferation [GO:0008284];
positive regulation of endothelial cell apoptotic process [GO:2000353];
positive regulation of protein kinase B signaling [GO:0051897];
positive regulation of reactive oxygen species metabolic process [GO:2000379];
progesterone metabolic process [GO:0042448];
prostaglandin metabolic process [GO:0006693];
protein import into nucleus, translocation [GO:0000060];
regulation of retinoic acid receptor signaling pathway [GO:0048385];
regulation of testosterone biosynthetic process [GO:2000224];
renal absorption [GO:0070293];
response to nutrient [GO:0007584];
retinal metabolic process [GO:0042574];
retinoid metabolic process [GO:0001523];
steroid metabolic process [GO:0008202];
testosterone biosynthetic process [GO:0061370]
Gene Ontology
(Molecular Function)
Complete annatation
15-hydroxyprostaglandin-D dehydrogenase, NADP+ activity [GO:0047020];
alditol:NADP+ 1-oxidoreductase activity [GO:0004032];
aldo-keto reductase, NADP activity [GO:0004033];
androsterone dehydrogenase activity [GO:0047023];
delta4-3-oxosteroid 5beta-reductase activity [GO:0047787];
dihydrotestosterone 17-beta-dehydrogenase activity [GO:0035410];
geranylgeranyl reductase activity [GO:0045550];
indanol dehydrogenase activity [GO:0047718];
ketoreductase activity [GO:0045703];
ketosteroid monooxygenase activity [GO:0047086];
NADP-retinol dehydrogenase activity [GO:0052650];
oxidoreductase activity, acting on NAD(PH, quinone or similar compound as acceptor [GO:0016655];
phenanthrene 9,10-monooxygenase activity [GO:0018636];
prostaglandin D2 11-ketoreductase activity [GO:0036131];
prostaglandin-F synthase activity [GO:0047017];
prostaglandin H2 endoperoxidase reductase activity [GO:0036130];
retinal dehydrogenase activity [GO:0001758];
retinol dehydrogenase activity [GO:0004745];
testosterone 17-beta-dehydrogenase, NADP+ activity [GO:0047045];
testosterone dehydrogenase, NAD+ activity [GO:0047035];
trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity [GO:0047115]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
extracellular exosome [GO:0070062];
intracellular [GO:0005622];
nucleus [GO:0005634]
Protein-protein interaction114196
Phylogenetic treeP42330
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-2.502739863054151.01623964798847e-091.46712298606152e-08
AZA vs. DISU1.057849954506640.1022124520424490.644788874295266
AZA vs. IL70.176568021733740.5364321711295630.999311006273513
AZA vs. SAHA0.300400744367090.4008440764333490.760129298280738
DISU vs. CD33.545450215285642.2474156367025e-061.97306600510504e-05
DISU vs. IL7-0.889118494813040.1574950453425840.514285678109196
DISU vs. SAHA-0.7556046461630050.2443998123734560.622848896550705
DMSO vs. AZA0.06118232431144970.8601593107327561
DMSO vs. CD32.541614254626635.39553401956994e-107.33607581270948e-09
DMSO vs. DISU-1.000391101679450.1170431675698910.594085730979542
DMSO vs. IL70.1225438068160190.6776269079576880.934273604905513
DMSO vs. SAHA0.2324008519756860.5200809077809380.824102204119421
HIV vs. Mock in Activationunknownunknownunknown
HIV vs. Mock in Latency-0.6677078789222780.001298964297568930.0789539831514275
IL7 vs. CD32.69464123473234.97712981939458e-131.52790789750987e-11
SAHA vs. CD32.775442479791512.27253327267363e-104.43614979523207e-09
SAHA vs. IL70.1152850140322010.7084890693299050.866537295652102
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.0277963 0.926363
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.064 1.348 1.567 1.654 1.457
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00157 NADH nutraceutical unknown unknown
DB01698 Rutin experimental unknown unknown
DB02056 (5e,13e)-9,15-Dihydroxy-11-Oxoprosta-5,13-Dien-1-Oicacid experimental unknown unknown
DB02266 Flufenamic Acid experimental unknown unknown
DB01536 4-Androstenedione experimental, illicit unknown inducer
DB03461 2&,39;-Monophosphoadenosine 5&,39;-Diphosphoribose experimental unknown unknown
DB07700 3-CARBOXAMIDO-1,3,5(10)-ESTRATRIEN-17(R)-SPIRO-2&,39;(5&,39;,5&,39;-DIMETHYL-6&,39;OXO)TETRAHYDROPYRAN experimental unknown unknown
DB00905 Bimatoprost approved, investigational unknown unknown
DB00997 Doxorubicin approved, investigational unknown substrate

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1RY0 X-ray 1.6Å A/B=1-323.
1RY8 X-ray 1.6Å A/B=1-323.
1S1P X-ray 1.2Å A=1-323.
1S1R X-ray 2.0Å A=1-323.
1S2A X-ray 1.7Å A=1-323.
1S2C X-ray 1.8Å A=1-323.
1XF0 X-ray 2.0Å A=1-323.
1ZQ5 X-ray 1.3Å A=1-323.
2F38 X-ray 2.0Å A=1-323.
2FGB X-ray 1.3Å A=1-323.
3R43 X-ray 2.0Å A=1-323.
3R58 X-ray 2.3Å A=1-323.
3R6I X-ray 1.9Å A=1-323.
3R7M X-ray 2.1Å A=1-323.
3R8G X-ray 1.8Å A=1-323.
3R8H X-ray 1.9Å A=1-323.
3R94 X-ray 2.0Å A=1-323.
3UFY X-ray 1.9Å A=1-323.
3UG8 X-ray 1.7Å A=1-323.
3UGR X-ray 1.6Å A=1-323.
3UWE X-ray 1.6Å A=1-323.
4DBS X-ray 1.8Å A/B=1-323.
4DBU X-ray 2.5Å A/B=1-323.
4DBW X-ray 1.8Å A/B=1-323.
4DZ5 X-ray 1.7Å A=1-323.
4FA3 X-ray 2.2Å A=1-323.
4FAL X-ray 2.0Å A=1-323.
4FAM X-ray 2.0Å A/B=1-323.
4H7C X-ray 1.9Å A=1-323.
4HMN X-ray 2.4Å A=1-323.
4WDT X-ray 1.5Å A=1-323.
4WDU X-ray 1.7Å A=1-323.
4WDW X-ray 1.9Å A/B=1-323.
4WDX X-ray 1.6Å A/B=1-323.
4WRH X-ray 1.6Å A=1-323.
4XVD X-ray 2.8Å A/B=1-323.
4XVE X-ray 1.5Å A=1-323.
4YVV X-ray 2.3Å A/B=1-323.
4YVX X-ray 2.3Å A/B=1-323.
4ZFC X-ray 2.0Å A/B=1-323.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00140 Steroid hormone biosynthesis - Homo sapiens (human)
hsa00590 Arachidonic acid metabolism - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)
hsa04913 Ovarian steroidogenesis - Homo sapiens (human)