Recombinant Human AKR1C3 Protein (C-6His)

Beta LifeScience SKU/CAT #: BL-0664NP
BL-0664NP: Greater than 95% as determined by reducing SDS-PAGE. (QC verified)
BL-0664NP: Greater than 95% as determined by reducing SDS-PAGE. (QC verified)

Recombinant Human AKR1C3 Protein (C-6His)

Beta LifeScience SKU/CAT #: BL-0664NP
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Product Overview

Description Recombinant Human Aldo-Keto Reductase Family 1 Member C3 is produced by our Mammalian expression system and the target gene encoding Met1-Tyr323 is expressed with a 6His tag at the C-terminus.
Accession P42330
Synonym Aldo-Keto Reductase Family 1 Member C3; 17-Beta-Hydroxysteroid Dehydrogenase Type 5; 17-Beta-HSD 5; 3-Alpha-HSD Type II Brain; 3-Alpha-Hydroxysteroid Dehydrogenase Type 2; 3-Alpha-HSD Type 2; Chlordecone Reductase Homolog HAKRb; Dihydrodiol Dehydrogenase 3; DD-3; DD3; Dihydrodiol Dehydrogenase Type I; HA1753; Indanol Dehydrogenase; Prostaglandin F Synthase; Testosterone 17-Beta-Dehydrogenase 5; Trans-1; 2-Dihydrobenzene-1; 2-Diol Dehydrogenase; AKR1C3; DDH1; HSD17B5; KIAA0119; PGFS
Gene Background AKR1C3, is an enzyme which belongs to the aldo/keto reductase family. It is expressed in many tissues including adrenal gland, brain, kidney, liver, lung, mammary gland, placenta, small intestine, colon, spleen, prostate and testis. AKR1C3 catalyzes the conversion of aldehydes and ketones to alcohols. It catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2,which functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. It can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites.
Molecular Mass 37.9 KDa
Apmol Mass 38 KDa, reducing conditions
Formulation Lyophilized from a 0.2 μm filtered solution of 20mM PB, 6% Sucrose, 2% Glycine, 100mM NaCl, 0.05% Tween 80,pH 6.0.
Endotoxin Less than 0.1 ng/µg (1 EU/µg) as determined by LAL test.
Purity Greater than 95% as determined by reducing SDS-PAGE. (QC verified)
Biological Activity Not tested
Reconstitution Always centrifuge tubes before opening. Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles.
Storage Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months.
Shipping The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature listed below.
Usage For Research Use Only

Target Details

Target Function Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Acts as a NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain and regulates the metabolism of androgens, estrogens and progesterone. Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH. Acts preferentially as a 17-ketosteroid reductase and has the highest catalytic efficiency of the AKR1C enzyme for the reduction of delta4-androstenedione to form testosterone. Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol. Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Displays also retinaldehyde reductase activity toward 9-cis-retinal.
Subcellular Location Cytoplasm.
Protein Families Aldo/keto reductase family
Database References
Tissue Specificity Expressed in many tissues including adrenal gland, brain, kidney, liver, lung, mammary gland, placenta, small intestine, colon, spleen, prostate and testis. High expression in prostate and mammary gland. In the prostate, higher levels in epithelial cells

Gene Functions References

  1. Genotype data on the AKR1C3 rs12529 SNP indicates that all three prostate cancer groups (New Zealanders, African Americans, and Caucasian Americans) have similar genotype and allele frequencies. The highest percentage of high-risk PC as a percentage of all PC were recorded for ever-smoker AA men with the AKR1C3 rs12529 CC genotype while the lowest was recorded for never-smoker NZ men with the CG+GG genotypes. PMID: 29920533
  2. AKR1C3 is a novel epithelial-mesenchymal transition driver in prostate cancer metastasis through activating ERK signaling. PMID: 30139661
  3. The GG genotype of AKR1C3 rs10508293 is associated with decreased risk for preeclampsia. PMID: 29777907
  4. AKR1C3 transcriptional regulation and its role in prostate cancer progression [review] PMID: 28359237
  5. Overexpression of AKR1C3 could result in the accumulation of prostaglandin F2alpha (PGF2alpha), which can not only promote prostate cancer cell 's proliferation but also could enhance prostate cancer cells resistance to radiation. PMID: 27385003
  6. The replacement of C154 with a residue possessing a bulky aromatic side-chain impairs the folding of the alpha-helix containing C154 and its neighboring secondary structures, leading to low thermostability of AKR1C3. PMID: 28025170
  7. Data suggest that, in breast cancer cells, expression of HSD17B5 and expression of GRP78 (an apoptosis inhibitor) are strongly but negatively correlated; GRP78 knockdown decreases breast cancer cell viability whereas HSD17B5 knockdown increases cell viability and cell proliferation. (HSD17B5, 17-beta-hydroxysteroid dehydrogenase 5; GRP78, 78 kDa glucose-regulated protein) PMID: 28457968
  8. AKR1C3 is the primary enzyme and CBR1 is a minor enzyme responsible for warfarin reduction in human liver cytosol. PMID: 27055738
  9. the present study suggests that AKR1C1, AKR1C2, AKR1C3, and AKR1C4 are closely associated with drug resistance to both CDDP and 5FU, and that mefenamic acid, an inhibitor of AKR1C, restores sensitivity through inhibition of drug-resistance in human cancer cells. PMID: 28259989
  10. a variant in the promoter region of HSD17B5 related to fetal androgen synthesis influences the genital phenotype in 21-Hydroxylase Deficiency females. PMID: 27082632
  11. Five common AKR1C3 polymorphisms were associated with decreased rates of exemestane catalysis. PMID: 27111237
  12. If our these findings can be reproduced in larger homogeneous cohorts, a genetic stratification based on the AKR1C3 rs12529 single nucleotide polymorphism, can minimize androgen deprivation therapy-related health-related quality of life effects in prostate cancer patients PMID: 27485119
  13. We identified strong associations between the studied AKR1C3 variants and UBC risk. The homozygous variant genotype of rs12529 was found to be inversely associated with UBC, and rs1937920 was shown to be associated with increased risk of UBC. None of the genotypes were found to be significantly associated with tumor characteristics. PMID: 27085562
  14. aldo-keto reductase 1C3-mediated prostaglandin D2 metabolism has a role in keloids PMID: 26308156
  15. The results suggest that decreased expression of AKR1C3 may be involved in development of gastric cancer and can be restored by Sodium Butyrate. PMID: 27019068
  16. AKR1C3 expression is elevated in prostate cancer cell lines and primary prostate cancer, suggesting a link between AKR1C3 levels and the epigenetic status in prostate cancer cells. PMID: 26429394
  17. Aldo-keto reductase 1C3 is overexpressed in skin squamous cell carcinoma (SCC). AKR1C3 affects SCC growth via prostaglandin metabolism. PMID: 24917395
  18. these results indicated that the actions of AKR1C3 can produce FP receptor ligands whose activation results in carcinoma cell survival in breast cancer. PMID: 26170067
  19. and AKR1C3 may serve as a valuable therapeutic target in the treatment of castration-resistant prostate cancer PMID: 25754347
  20. AKR1C3 activation is a critical resistance mechanism associated with enzalutamide resistance. PMID: 25649766
  21. In the present study, crystal structures of complexes of HSD17B5 with structurally diverse inhibitors derived from high-throughput screening were determined. PMID: 25849402
  22. AKR1C3 mRNA expression did not differ between bipolar disorder patients in any affective state or in comparison with healthy control subjects. PMID: 25522430
  23. A catalysis-independent role for AKR1C3 on AR activity via Siah2 has been identified. PMID: 26160177
  24. AKR1C3 mediated doxorubicin resistance might be resulted from the activation of anti-apoptosis PTEN/Akt pathway via PTEN loss. PMID: 25661377
  25. Findings indicate the potential involvement of aldo-keto reductase AKR1C3 in the acquired radioresistance by AKR1C3 overexpression. PMID: 25419901
  26. Higher expression of PLA2G2A, PTGS2, AKR1B1, AKR1C3 and ABCC4 was seen in 22-B endometriosis cells. PMID: 25446850
  27. P450c17 and AKR1C3 inhibition may be an effective combinatorial treatment strategy. PMID: 25514466
  28. AKR1C3 2 G allele carriers exhibited greater increases in heart rate and stimulant and sedative effects of alcohol than C allele homozygotes PMID: 24838369
  29. Data suggest that reduction of daunorubicin/idarubicin is catalyzed by AKR1C3 and contributes to resistance of carcinoma cells to these anthracyclines; expression of AKR1C3 is induced in carcinoma cells following exposure to daunorubicin/idarubicin. PMID: 24832494
  30. AKR1C3 can serve as a promising biomarker for the progression of prostate cancer PMID: 24571686
  31. The -71G HSD17B5 variant is not a major component of the molecular pathogenetic mechanisms of PCOS, although it might contribute to the severity of hyperandrogenemia in women with PCOS and biochemical hyperandrogenism. PMID: 18692800
  32. Significantly higher levels of SRD5A1, AKR1C2, AKR1C3, and HSD17B10 mRNA were however found in bone metastases than in non-malignant and/or malignant prostate tissue PMID: 24244276
  33. Report expression of AKR1C3 in neuroendocrine tumors and adenocarcinomas of pancreas, gastrointestinal tract, and lung. PMID: 24228104
  34. Silencing of AKR1C3 increases LCN2 expression and inhibits metastasis in cervical cancer. PMID: 24316309
  35. Data indicate that fallopian tube and the epithelial component of Brenner tumours (BTs) expressed AKR1C3 and androgen receptor, but the tumour stromal cells showed strong expression of calretinin, inhibin and steroidogenic factor 1 in the majority of BTs. PMID: 24012099
  36. Correlation of aldo-ketoreductase (AKR) 1C3 genetic variant with doxorubicin pharmacodynamics in Asian breast cancer patients. PMID: 23116553
  37. examine the evidence that supports the vital role of AKR1C3 in CRPC and recent developments in the discovery of potent and selective AKR1C3 inhibitors PMID: 23748150
  38. AKR1C3-mediated radioresistance in lung cancer cells is correlated with an arrest in the G2/M cell cycle and a decreased induction of apoptosis. PMID: 23519145
  39. The involvement of up-regulated AKR1C1, AKR1C3 and proteasome in CDDP resistance of colon cancers. PMID: 23165153
  40. Affect further reduction of 3-keto and 20-keto groups catalyzed by AKR1C2 and AKR1C3. PMID: 23183084
  41. AKR1C3 can be considered a therapeutic target in a subgroup of patients with high AKR1C3 expression. PMID: 23196782
  42. Our data suggest that there is no association of HSD17B6 and HSD17B5 variants with the occurrence of Polycystic Ovary Syndrome in the Chinese population PMID: 21039282
  43. Activin A stimulates AKR1C3 expression and growth in human prostate cancer PMID: 23024260
  44. AKR1C3 immunoreactivity was extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction, but not in small cell carcinoma. PMID: 22670171
  45. determined the X-ray crystal structure of AKR1C3 with the cofactor NADP+ and the drug-like inhibitor 3-phenoxybenzoic acid bound at a resolution of 1.68 A degrees in space group P212121 PMID: 22505408
  46. AKR1C3 functions in differentiation-associated gene regulation and also has a role in supporting inflammation in atopic dermatitis. PMID: 22170488
  47. Evidence of association of two alleles for alcohol dependence (AD) is found in SRD5A1 and AKR1C3, mediating a protective effect of the minor allele at each AD marker based on the genotype of the second marker. PMID: 21323680
  48. the pro-proliferative action of AKR1C3 in HL-60 cells involves the retinoic acid signalling pathway and that this is in part due to the retinaldehyde reductase activity of AKR1C3 PMID: 21851338
  49. role of AKR1C3 in the metabolism of testosterone and progesterone via the 5beta-reductase pathway. PMID: 21521174
  50. enhanced metabolism of progesterone by SRD5A1 and the 20alpha-HSD and 3alpha/beta-HSD activities of AKR1C1, AKR1C2 and AKR1C3 PMID: 21232532

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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