AKR1C3
Aldo-keto reductase family 1, member C3 |
---|
PDB rendering based on 1ry0. |
Available structures |
PDB |
Ortholog search: PDBe, RCSB |
List of PDB id codes |
1RY0, 1RY8, 1S1P, 1S1R, 1S2A, 1S2C, 1XF0, 1ZQ5, 2F38, 2FGB, 3R43, 3R58, 3R6I, 3R7M, 3R8G, 3R8H, 3R94, 3UFY, 3UG8, 3UGR, 3UWE, 4DBS, 4DBU, 4DBW, 4DZ5, 4FA3, 4FAL, 4FAM, 4H7C, 4HMN, 4WDT, 4WDU, 4WDW, 4WDX, 4WRH, 4XVD, 4XVE
|
|
|
Identifiers |
---|
Symbols |
AKR1C3 ; DD3; DDX; HA1753; HAKRB; HAKRe; HSD17B5; PGFS; hluPGFS |
---|
External IDs |
OMIM: 603966 MGI: 2145420 HomoloGene: 128661 ChEMBL: 4681 GeneCards: AKR1C3 Gene |
---|
EC number |
1.1.1.112, 1.1.1.188, 1.1.1.239, 1.1.1.357, 1.1.1.64, 1.3.1.20 |
---|
|
RNA expression pattern |
---|
|
|
More reference expression data |
Orthologs |
---|
Species |
Human |
Mouse |
---|
Entrez |
8644 |
105349 |
---|
Ensembl |
ENSG00000196139 |
ENSMUSG00000021214 |
---|
UniProt |
P42330 |
Q8K023 |
---|
RefSeq (mRNA) |
NM_001253908 |
NM_134066 |
---|
RefSeq (protein) |
NP_001240837 |
NP_598827 |
---|
Location (UCSC) |
Chr 10: 5.04 – 5.11 Mb |
Chr 13: 4.13 – 4.15 Mb |
---|
PubMed search |
|
|
---|
|
Aldo-keto reductase family 1 member C3 is a key steroidogenic enzyme that in humans is encoded by the AKR1C3 gene.[1][2][3]
Function
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.[3]
Pathology
AKR1C3 is overexpressed in prostate cancer (PCa) and is associated with the development of castration-resistant prostate cancer (CRPC). In addition, AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression.[4]
References
- ↑ Khanna M, Qin KN, Wang RW, Cheng KC (Aug 1995). "Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases". The Journal of Biological Chemistry 270 (34): 20162–8. doi:10.1074/jbc.270.34.20162. PMID 7650035.
- ↑ Matsuura K, Shiraishi H, Hara A, Sato K, Deyashiki Y, Ninomiya M, Sakai S (Nov 1998). "Identification of a principal mRNA species for human 3alpha-hydroxysteroid dehydrogenase isoform (AKR1C3) that exhibits high prostaglandin D2 11-ketoreductase activity". Journal of Biochemistry 124 (5): 940–6. doi:10.1093/oxfordjournals.jbchem.a022211. PMID 9792917.
- 1 2 "Entrez Gene: AKR1C3 aldo-keto reductase family 1, member C3 (3-alpha hydroxysteroid dehydrogenase, type II)".
- ↑ Tian Y, Zhao L, Zhang H, Liu X, Zhao L, Zhao X, Li Y, Li J (2014). "AKR1C3 overexpression may serve as a promising biomarker for prostate cancer progression". Diagnostic Pathology 9 (1): 42. doi:10.1186/1746-1596-9-42. PMC 3939640. PMID 24571686.
Further reading
- Lin SX, Shi R, Qiu W, Azzi A, Zhu DW, Dabbagh HA, Zhou M (Mar 2006). "Structural basis of the multispecificity demonstrated by 17beta-hydroxysteroid dehydrogenase types 1 and 5". Molecular and Cellular Endocrinology 248 (1-2): 38–46. doi:10.1016/j.mce.2005.11.035. PMID 16480815.
- Khanna M, Qin KN, Cheng KC (Jun 1995). "Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans". The Journal of Steroid Biochemistry and Molecular Biology 53 (1-6): 41–6. doi:10.1016/0960-0760(95)00019-V. PMID 7626489.
- Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y, Kotani H (1995). "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". DNA Research 2 (1): 37–43. doi:10.1093/dnares/2.1.37. PMID 7788527.
- Khanna M, Qin KN, Klisak I, Belkin S, Sparkes RS, Cheng KC (Jan 1995). "Localization of multiple human dihydrodiol dehydrogenase (DDH1 and DDH2) and chlordecone reductase (CHDR) genes in chromosome 10 by the polymerase chain reaction and fluorescence in situ hybridization". Genomics 25 (2): 588–90. doi:10.1016/0888-7543(95)80066-U. PMID 7789999.
- Qin KN, New MI, Cheng KC (Dec 1993). "Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase". The Journal of Steroid Biochemistry and Molecular Biology 46 (6): 673–9. doi:10.1016/0960-0760(93)90308-J. PMID 8274401.
- Bennett MJ, Schlegel BP, Jez JM, Penning TM, Lewis M (Aug 1996). "Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP+". Biochemistry 35 (33): 10702–11. doi:10.1021/bi9604688. PMID 8718859.
- Lin HK, Jez JM, Schlegel BP, Peehl DM, Pachter JA, Penning TM (Dec 1997). "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". Molecular Endocrinology 11 (13): 1971–84. doi:10.1210/me.11.13.1971. PMID 9415401.
- Mills KI, Gilkes AF, Sweeney M, Choudhry MA, Woodgate LJ, Bunce CM, Brown G, Burnett AK (Nov 1998). "Identification of a retinoic acid responsive aldoketoreductase expressed in HL60 leukaemic cells". FEBS Letters 440 (1-2): 158–62. doi:10.1016/S0014-5793(98)01435-5. PMID 9862446.
- Dufort I, Rheault P, Huang XF, Soucy P, Luu-The V (Feb 1999). "Characteristics of a highly labile human type 5 17beta-hydroxysteroid dehydrogenase". Endocrinology 140 (2): 568–74. doi:10.1210/en.140.2.568. PMID 9927279.
- Rheault P, Dufort I, Soucy P, Luu-The V (1999). "Assignment of HSD17B5 encoding type 5 17 beta-hydroxysteroid dehydrogenase to human chromosome bands 10p15-->p14 and mouse chromosome 13 region A2 by in situ hybridization: identification of a new syntenic relationship". Cytogenetics and Cell Genetics 84 (3-4): 241–2. doi:10.1159/000015267. PMID 10393440.
- Griffin LD, Mellon SH (Nov 1999). "Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes". Proceedings of the National Academy of Sciences of the United States of America 96 (23): 13512–7. doi:10.1073/pnas.96.23.13512. PMC 23979. PMID 10557352.
- Suzuki-Yamamoto T, Nishizawa M, Fukui M, Okuda-Ashitaka E, Nakajima T, Ito S, Watanabe K (Dec 1999). "cDNA cloning, expression and characterization of human prostaglandin F synthase". FEBS Letters 462 (3): 335–40. doi:10.1016/S0014-5793(99)01551-3. PMID 10622721.
- Nishizawa M, Nakajima T, Yasuda K, Kanzaki H, Sasaguri Y, Watanabe K, Ito S (Feb 2000). "Close kinship of human 20alpha-hydroxysteroid dehydrogenase gene with three aldo-keto reductase genes". Genes to Cells 5 (2): 111–25. doi:10.1046/j.1365-2443.2000.00310.x. PMID 10672042.
- Penning TM, Burczynski ME, Jez JM, Hung CF, Lin HK, Ma H, Moore M, Palackal N, Ratnam K (Oct 2000). "Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones". The Biochemical Journal 351 (Pt 1): 67–77. doi:10.1042/0264-6021:3510067. PMC 1221336. PMID 10998348.
- Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
- Penning TM, Burczynski ME, Jez JM, Lin HK, Ma H, Moore M, Ratnam K, Palackal N (Jan 2001). "Structure-function aspects and inhibitor design of type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3)". Molecular and Cellular Endocrinology 171 (1-2): 137–49. doi:10.1016/S0303-7207(00)00426-3. PMID 11165022.
- Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (Sep 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
PDB gallery |
---|
| | 1ry0: Structure of prostaglandin F synthase with prostaglandin D2 |
| 1ry8: Prostaglandin F synthase complexed with NADPH and rutin |
| 1s1p: Crystal structures of prostaglandin D2 11-ketoreductase (AKR1C3) in complex with the non-steroidal anti-inflammatory drugs flufenamic acid and indomethacin |
| 1s1r: Crystal structures of prostaglandin D2 11-ketoreductase (AKR1C3) in complex with the non-steroidal anti-inflammatory drugs flufenamic acid and indomethacin |
| 1s2a: Crystal structures of prostaglandin D2 11-ketoreductase in complex with the non-steroidal anti-inflammatory drugs flufenamic acid and indomethacin |
| 1s2c: Crystal structures of prostaglandin D2 11-ketoreductase in complex with the non-steroidal anti-inflammatory drugs flufenamic acid and indomethacin |
| 1xf0: Crystal structure of human 17beta-hydroxysteroid dehydrogenase type 5 (AKR1C3) complexed with delta4-androstene-3,17-dione and NADP |
| 1zq5: Crystal structure of human androgenic 17beta-hydroxysteroid dehydrogenase type 5 in complexed with a potent inhibitor EM1404 |
| 2f38: Crystal structure of prostaglandin F synathase containing bimatoprost |
| 2fgb: Crystal structure of human 17bet a-hydroxysteroid dehydrogenase type 5 in complexes with PEG and NADP |
|
|
|
|
---|
| Receptor (ligands) | DP (D2) | | |
---|
| |
- Antagonists: ADC-3680
- AZD-1981
- Bay U3405
- Fevipiprant
- MK-1029
- MK-7246
- OC-459
- OC000459
- QAV-680
- Ramatroban
- Setipiprant
- TM30089
- Vidupiprant
|
---|
|
---|
| EP (E2) | |
- Antagonists: AH-6809
- ONO-8130
- SC-19220
- SC-51089
- SC-51322
|
---|
| |
- Antagonists: AH-6809
- PF-04418948
- TG 4-155
|
---|
| | |
---|
| |
- Antagonists: GW-627368
- L-161982
- ONO-AE3-208
|
---|
| Unsorted | |
---|
|
---|
| FP (F2α) | |
---|
| IP (I2) | |
---|
| TP (TXA2) | |
---|
| Unsorted |
- Arbaprostil
- Ataprost
- Ciprostene
- Clinprost
- Cobiprostone
- Delprostenate
- Deprostil
- Dimoxaprost
- Doxaprost
- Ecraprost
- Eganoprost
- Enisoprost
- Eptaloprost
- Esuberaprost
- Etiproston
- Fenprostalene
- Flunoprost
- Froxiprost
- Lanproston
- Limaprost
- Luprostiol
- Meteneprost
- Mexiprostil
- Naxaprostene
- Nileprost
- Nocloprost
- Ornoprostil
- Oxoprostol
- Penprostene
- Pimilprost
- Piriprost
- Posaraprost
- Prostalene
- Rioprostil
- Rivenprost
- Rosaprostol
- Spiriprostil
- Tiaprost
- Tilsuprost
- Tiprostanide
- Trimoprostil
- Viprostol
|
---|
|
---|
| Enzyme (inhibitors) | |
---|
| Others | |
---|
| See also: Leukotrienergics |
|
|
---|
| Activity | |
---|
| Regulation | |
---|
| Classification | |
---|
| Types | |
---|
|