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AKR1C3 aldo-keto reductase family 1 member C3 [ Homo sapiens (human) ]

Gene ID: 8644, updated on 11-Apr-2024

Summary

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Official Symbol
AKR1C3provided by HGNC
Official Full Name
aldo-keto reductase family 1 member C3provided by HGNC
Primary source
HGNC:HGNC:386
See related
Ensembl:ENSG00000196139 MIM:603966; AllianceGenome:HGNC:386
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
DD3; DDX; PGFS; HAKRB; HAKRe; HA1753; HSD17B5; hluPGFS
Summary
This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ), and the oxidation of 9alpha,11beta-PGF2 to PGD2. It may play an important role in the pathogenesis of allergic diseases such as asthma, and may also have a role in controlling cell growth and/or differentiation. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
Expression
Broad expression in duodenum (RPKM 122.7), gall bladder (RPKM 91.1) and 15 other tissues See more
Orthologs
all
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Genomic context

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Location:
10p15.1
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (5048781..5107686)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (5049294..5108188)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (5090973..5149878)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124902365 Neighboring gene aldo-keto reductase family 1 member C1 Neighboring gene uncharacterized LOC101928051 Neighboring gene aldo-keto reductase family 1 member C2 Neighboring gene CRISPRi-validated cis-regulatory element chr10.193 Neighboring gene uncharacterized LOC107984198 Neighboring gene uncharacterized LOC124902366 Neighboring gene Sharpr-MPRA regulatory region 11333 Neighboring gene U8 small nucleolar RNA Neighboring gene Sharpr-MPRA regulatory region 1972 Neighboring gene aldo-keto reductase family 1 member C8 Neighboring gene MPRA-validated peak852 silencer Neighboring gene MPRA-validated peak853 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr10:5241916-5242139 Neighboring gene aldo-keto reductase family 1 member C4 Neighboring gene ADP ribosylation factor like GTPase 4A pseudogene 3

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. AKR1C3 suppresses ferroptosis in hepatocellular carcinoma through regulation of YAP/SLC7A11 signaling pathway. Chen J, et al. Mol Carcinog, 2023 Jun. PMID 36920042
  2. Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer. Cui X, et al. Int J Mol Sci, 2023 Feb 24. PMID 36901944, Free PMC Article
  3. Influence of aldo-keto reductase 1C3 polymorphisms in early-onset female psoriasis patients. Nojiri Y, et al. Sci Rep, 2023 Feb 25. PMID 36841845, Free PMC Article
  4. AKR1C3-dependent lipid droplet formation confers hepatocellular carcinoma cell adaptability to targeted therapy. Wu C, et al. Theranostics, 2022. PMID 36451864, Free PMC Article
  5. Plasma Exosomal AKR1C3 mRNA Expression Is a Predictive and Prognostic Biomarker in Patients with Metastatic Castration-Resistant Prostate Cancer. Zhu S, et al. Oncologist, 2022 Nov 3. PMID 36067250, Free PMC Article

See all (192) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. AKR1C3 silencing inhibits autophagy-dependent glycolysis in thyroid cancer cells by inactivating ERK signaling.
    Title: AKR1C3 silencing inhibits autophagy-dependent glycolysis in thyroid cancer cells by inactivating ERK signaling.
  2. Inhibition of aldo-keto reductase 1C3 overcomes gemcitabine/cisplatin resistance in bladder cancer.
    Title: Inhibition of aldo-keto reductase 1C3 overcomes gemcitabine/cisplatin resistance in bladder cancer.
  3. Aldo-keto reductase family member C3 (AKR1C3) promotes hepatocellular carcinoma cell growth by producing prostaglandin F2alpha.
    Title: Aldo-keto reductase family member C3 (AKR1C3) promotes hepatocellular carcinoma cell growth by producing prostaglandin F2α.
  4. Keratinocytes Exposed to Blue or Red Light: Proteomic Characterization Showed Cytoplasmic Thioredoxin Reductase 1 and Aldo-Keto Reductase Family 1 Member C3 Triggered Expression.
    Title: Keratinocytes Exposed to Blue or Red Light: Proteomic Characterization Showed Cytoplasmic Thioredoxin Reductase 1 and Aldo-Keto Reductase Family 1 Member C3 Triggered Expression.
  5. In Vitro Evaluation of the Reductase Activities of Human AKR1C3 Allelic Variants.
    Title: In Vitro Evaluation of the Reductase Activities of Human AKR1C3 Allelic Variants.
  6. AKR1C3 suppresses ferroptosis in hepatocellular carcinoma through regulation of YAP/SLC7A11 signaling pathway.
    Title: AKR1C3 suppresses ferroptosis in hepatocellular carcinoma through regulation of YAP/SLC7A11 signaling pathway.
  7. Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer.
    Title: Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer.
  8. Availability of aldo-keto reductase 1C3 and ATP-binding cassette B1 as therapeutic targets for alleviating paclitaxel resistance in breast cancer MCF7 cells.
    Title: Availability of aldo-keto reductase 1C3 and ATP-binding cassette B1 as therapeutic targets for alleviating paclitaxel resistance in breast cancer MCF7 cells.
  9. Influence of aldo-keto reductase 1C3 polymorphisms in early-onset female psoriasis patients.
    Title: Influence of aldo-keto reductase 1C3 polymorphisms in early-onset female psoriasis patients.
  10. AKR1C3-dependent lipid droplet formation confers hepatocellular carcinoma cell adaptability to targeted therapy.
    Title: AKR1C3-dependent lipid droplet formation confers hepatocellular carcinoma cell adaptability to targeted therapy.
Submit: New GeneRIF Correction See all GeneRIFs (130)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Human metabolic individuality in biomedical and pharmaceutical research.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • KIAA0119

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables 5alpha-androstane-3beta,17beta-diol dehydrogenase activity IEA
Inferred from Electronic Annotation
more info
  
enables aldo-keto reductase (NADPH) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables aldo-keto reductase (NADPH) activity TAS
Traceable Author Statement
more info
  
enables aldose reductase (NADPH) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables aldose reductase (NADPH) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables all-trans-retinol dehydrogenase (NAD+) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables all-trans-retinol dehydrogenase (NADP+) activity TAS
Traceable Author Statement
more info
  
enables androstan-3-alpha,17-beta-diol dehydrogenase activity IEA
Inferred from Electronic Annotation
more info
  
enables androsterone dehydrogenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables androsterone dehydrogenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables bile acid binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables delta4-3-oxosteroid 5beta-reductase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables dihydrotestosterone 17-beta-dehydrogenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables estradiol 17-beta-dehydrogenase [NAD(P)] activity IEA
Inferred from Electronic Annotation
more info
  
enables geranylgeranyl reductase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ketoreductase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ketosteroid monooxygenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ketosteroid monooxygenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor IDA
Inferred from Direct Assay
more info
 PubMed 
enables phenanthrene 9,10-monooxygenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables prostaglandin D2 11-ketoreductase activity TAS
Traceable Author Statement
more info
  
enables prostaglandin H2 endoperoxidase reductase activity TAS
Traceable Author Statement
more info
  
enables prostaglandin-F synthase activity IEA
Inferred from Electronic Annotation
more info
  
enables retinal dehydrogenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables testosterone 17-beta-dehydrogenase (NADP+) activity IEA
Inferred from Electronic Annotation
more info
  
enables testosterone dehydrogenase (NAD+) activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to calcium ion IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to corticosteroid stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to jasmonic acid stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to prostaglandin D stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to prostaglandin stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to starvation IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in cyclooxygenase pathway TAS
Traceable Author Statement
more info
  
involved_in daunorubicin metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in daunorubicin metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in doxorubicin metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in doxorubicin metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in farnesol catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in keratinocyte differentiation IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in macromolecule metabolic process IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in male gonad development IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in negative regulation of retinoic acid biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of cell population proliferation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of cell population proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of endothelial cell apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of reactive oxygen species metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in progesterone metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in progesterone metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in prostaglandin metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in prostaglandin metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in prostaglandin metabolic process IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in regulation of retinoic acid receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of testosterone biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in renal absorption NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in response to nutrient IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in retinal metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in retinoid metabolic process TAS
Traceable Author Statement
more info
  
involved_in retinol metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in steroid metabolic process IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in testosterone biosynthetic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
aldo-keto reductase family 1 member C3
Names
3-alpha hydroxysteroid dehydrogenase, type II
3-alpha-HSD type II, brain
chlordecone reductase homolog HAKRb
dihydrodiol dehydrogenase 3
dihydrodiol dehydrogenase X
indanol dehydrogenase
prostaglandin F synthase
testosterone 17-beta-dehydrogenase 5
trans-1,2-dihydrobenzene-1,2-diol dehydrogenase
type IIb 3-alpha hydroxysteroid dehydrogenase
NP_001240837.1
NP_001240838.1
NP_003730.4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_047094.1 RefSeqGene

    Range
    50649..63921
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001253908.2 → NP_001240837.1  aldo-keto reductase family 1 member C3 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is the same length as isoform 1 but differs by 1 aa in the N-terminus.
    Source sequence(s)
    BC019230, BG547635, H79159
    Consensus CDS
    CCDS73062.1
    UniProtKB/TrEMBL
    A0A0A0MSS8, Q2XPP3
    Related
    ENSP00000401327.3, ENST00000439082.7
    Conserved Domains (2) summary
    COG0656
    Location:9 → 305
    ARA1; Aldo/keto reductase, related to diketogulonate reductase [Secondary metabolites biosynthesis, transport and catabolism]
    COG0667
    Location:17 → 297
    Tas; Predicted oxidoreductase (related to aryl-alcohol dehydrogenase) [General function prediction only]

  2. NM_001253909.2 → NP_001240838.1  aldo-keto reductase family 1 member C3 isoform 3

    See identical proteins and their annotated locations for NP_001240838.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks several exons at its 3' end, which extends into an intron compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AK296701, AL391427
    UniProtKB/TrEMBL
    B4DKT3
    Related
    ENST00000480697.6
    Conserved Domains (2) summary
    COG0656
    Location:8 → 134
    ARA1; Aldo/keto reductase, related to diketogulonate reductase [Secondary metabolites biosynthesis, transport and catabolism]
    COG0667
    Location:17 → 119
    Tas; Predicted oxidoreductase (related to aryl-alcohol dehydrogenase) [General function prediction only]

  3. NM_003739.6 → NP_003730.4  aldo-keto reductase family 1 member C3 isoform 1

    See identical proteins and their annotated locations for NP_003730.4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes one of the larger isoforms (1).
    Source sequence(s)
    AV761799, BC019230
    Consensus CDS
    CCDS7063.1
    UniProtKB/Swiss-Prot
    A8K2V0, B4DL37, P42330, Q5T2L1, Q96DJ1, Q96KI8, Q99530, Q9UCX1, Q9UII3, Q9UKL9
    UniProtKB/TrEMBL
    Q2XPP3
    Related
    ENSP00000369927.3, ENST00000380554.5
    Conserved Domains (1) summary
    cd19108
    Location:6 → 306
    AKR_AKR1C1-35; AKR1C family of aldo-keto reductase (AKR)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

    Range
    5048781..5107686
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060934.1 Alternate T2T-CHM13v2.0

    Range
    5049294..5108188
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_016253.1: Suppressed sequence

    Description
    NM_016253.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P42330.4 GenPept UniProtKB/Swiss-Prot:P42330

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Other Literature Sources
Chemical Information
Molecular Biology Databases
Research Materials
Tools
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