Protein-coding gene in the species Homo sapiens
AKR1C2 |
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Available structures |
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PDB | Ortholog search: PDBe RCSB |
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List of PDB id codes |
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1IHI, 1J96, 1XJB, 2HDJ, 2IPJ, 4JQ1, 4JQ2, 4JQ3, 4JQ4, 4JQA, 4JTQ, 4JTR, 4L1W, 4L1X, 4XO6, 4XO7 |
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Identifiers |
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Aliases | AKR1C2, AKR1C-pseudo, BABP, DD, DD2, DDH2, HAKRD, HBAB, MCDR2, SRXY8, TDD, DD-2, DD/BABP, aldo-keto reductase family 1, member C2, aldo-keto reductase family 1 member C2 |
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External IDs | OMIM: 600450; MGI: 1924587; HomoloGene: 134114; GeneCards: AKR1C2; OMA:AKR1C2 - orthologs |
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EC number | 1.1.1.357 |
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Gene location (Human) |
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![Chromosome 10 (human)](//upload.wikimedia.org/wikipedia/commons/thumb/2/2f/Ideogram_human_chromosome_10.svg/300px-Ideogram_human_chromosome_10.svg.png) | Chr. | Chromosome 10 (human)[1] |
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| Band | 10p15.1 | Start | 4,987,775 bp[1] |
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End | 5,018,031 bp[1] |
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Gene location (Mouse) |
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![Chromosome 13 (mouse)](//upload.wikimedia.org/wikipedia/commons/thumb/0/04/Ideogram_house_mouse_chromosome_13.svg/260px-Ideogram_house_mouse_chromosome_13.svg.png) | Chr. | Chromosome 13 (mouse)[2] |
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| Band | 13|13 A1 | Start | 4,624,074 bp[2] |
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End | 4,636,540 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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Top expressed in | - islet of Langerhans
- right lobe of liver
- olfactory zone of nasal mucosa
- gallbladder
- gastrocnemius muscle
- Descending thoracic aorta
- ascending aorta
- muscle of thigh
- left coronary artery
- minor salivary glands
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| Top expressed in | - right kidney
- human kidney
- proximal tubule
- morula
- embryo
- primary oocyte
- primary visual cortex
- secondary oocyte
- blastocyst
- muscle of thigh
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| More reference expression data |
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BioGPS | |
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Gene ontology |
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Molecular function | - trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
- alditol:NADP+ 1-oxidoreductase activity
- phenanthrene 9,10-monooxygenase activity
- oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor
- bile acid binding
- carboxylic acid binding
- oxidoreductase activity
- ketosteroid monooxygenase activity
- alcohol dehydrogenase (NADP+) activity
- steroid dehydrogenase activity
| Cellular component | | Biological process | - prostaglandin metabolic process
- G protein-coupled receptor signaling pathway
- cellular response to jasmonic acid stimulus
- steroid metabolic process
- positive regulation of protein kinase B signaling
- epithelial cell differentiation
- daunorubicin metabolic process
- doxorubicin metabolic process
- lipid metabolism
- progesterone metabolic process
- digestion
- cellular response to prostaglandin D stimulus
- positive regulation of cell population proliferation
| Sources:Amigo / QuickGO |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | |
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NM_001135241 NM_001354 NM_205845 NM_001321027 NM_001393392 |
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RefSeq (protein) | |
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NP_001128713 NP_001307956 NP_001345 NP_995317 |
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Location (UCSC) | Chr 10: 4.99 – 5.02 Mb | Chr 13: 4.62 – 4.64 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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Aldo-keto reductase family 1 member C2, also known as bile acid binding protein, 3α-hydroxysteroid dehydrogenase type 3 (3α-HSD3),[5][6] and dihydrodiol dehydrogenase type 2, is an enzyme that in humans is encoded by the AKR1C2 gene.[7]
Superfamily of enzymes
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 using NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This particular enzyme, AKR1C2, binds bile acid with high affinity, and shows minimal 3α-hydroxysteroid dehydrogenase activity. The AKR1C2 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 two different isoforms have been found for this gene.[7] The AKR1C2 enzyme catalyzes reactions at specific positions on the steroid nucleus. Specifically, AKR enzymes, including AKR1C2, act as 3α/β-HSDs, 17β-HSDs, and 20α-HSDs, catalyzing NAD(P)(H)-dependent oxidoreduction of substituents at the C3, C17, and C20 positions of the steroid nucleus.[8][9][10]
Aldo-keto reductase activity
AKR1C2 binds bile acid with high affinity catalyzing aldo-keto reduction reaction.[7]
Aldo-keto reductases, including AKR1C2, are NAD(P)H-linked oxidoreductases that primarily catalyze the reduction of aldehydes and ketones to primary and secondary alcohols. This reduction is dependent on NADPH.[11][12]
In the context of bile acids, the AKR1C2 enzyme would bind to the bile acid (a type of steroid molecule) and catalyze the reduction of a carbonyl group (C=O) present in the bile acid to a hydroxy group (-OH), using NADPH as a cofactor.[11][12] This reaction is part of the broader metabolic processes that these enzymes are involved in, which include biosynthesis, intermediary metabolism, and detoxification.[11][12]
3α-hydroxysteroid dehydrogenase activity
The AKR1C2 enzyme is also known as 3α-hydroxysteroid dehydrogenase type 3 (3α-HSD3), meaning that the enzyme possesses 3α-hydroxysteroid dehydrogenase activity, i.e. it can hydroxylate steroids at a carbon position 3α of the steroid nucleus, attaching the hydroxy group (-OH) to carbon 3 in α stereiodirection. 3α-hydroxysteroid dehydrogenases, including AKR1C2, are NAD(P)H-linked oxidoreductases that primarily catalyze the oxidation of 3α-hydroxysteroids to their corresponding 3-ketosteroids. This oxidation is dependent on NAD+. The substrates for the 3α-HSD3 enzyme are steroids such as androgens, estrogens, and progestins, which regulate various sex functions. For example, 3α-HSD3 can catalyze the conversion of the potent androgen 5α-dihydrotestosterone (DHT) into its much less active form, 5α-androstan-3α,17β-diol (3α-diol), effectively deactivating biological action of DHT.[13][14][15][16]
Isozymes of aldo-keto reductase family 1 member C
HGNC Gene Symbol | Enzyme Name Aliases[17] |
AKR1C1 | aldo-keto reductase family 1 member C1; 20α-hydroxysteroid dehydrogenase |
AKR1C2 | aldo-keto reductase family 1 member C2; 3α-hydroxysteroid dehydrogenase type 3 |
AKR1C3 | aldo-keto reductase family 1 member C3; 3α-hydroxysteroid dehydrogenase type 2; 17β-hydroxysteroid dehydrogenase type 5; HSD17B5 |
AKR1C4 | aldo-keto reductase family 1 member C4; 3α-hydroxysteroid dehydrogenase type 1 |
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000151632 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021207 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Zhang B, Zhu DW, Hu XJ, Zhou M, Shang P, Lin SX (2014). "Human 3-alpha hydroxysteroid dehydrogenase type 3 (3α-HSD3): The V54L mutation restricting the steroid alternative binding and enhancing the 20α-HSD activity". The Journal of Steroid Biochemistry and Molecular Biology. 141: 135–143. doi:10.1016/j.jsbmb.2014.01.003. PMID 24434280.
- ^ Li T, Zhang W, Lin SX (2020). "Steroid enzyme and receptor expression and regulations in breast tumor samples – A statistical evaluation of public data". The Journal of Steroid Biochemistry and Molecular Biology. 196. doi:10.1016/j.jsbmb.2019.105494. PMID 31610224. Archived from the original on 2024-04-17. Retrieved 2024-04-08.
- ^ a b c "Entrez Gene: AKR1C2 aldo-keto reductase family 1, member C2 (dihydrodiol dehydrogenase 1; 20-alpha (3-alpha)-hydroxysteroid dehydrogenase)". National Center for Biotechnology Information, U.S. National Library of Medicine. Archived from the original on 2019-03-29.
This article incorporates text from this source, which is in the public domain. - ^ Feder HH (1981). "Essentials of Steroid Structure, Nomenclature, Reactions, Biosynthesis, and Measurements". Neuroendocrinology of Reproduction. pp. 19–63. doi:10.1007/978-1-4684-3875-8_3. ISBN 978-1-4684-3875-8.
- ^ Penning TM, Wangtrakuldee P, Auchus RJ (20 August 2018). "Structural and Functional Biology of Aldo-Keto Reductase Steroid-Transforming Enzymes". Endocrine Reviews. 40 (2): 447–475. doi:10.1210/er.2018-00089. PMC 6405412. PMID 30137266.
- ^ Zhou Y, Lin Y, Li W, Liu Q, Gong H, Li Y, Luo D (February 2023). "Expression of AKRs superfamily and prognostic in human gastric cancer". Medicine (Baltimore). 102 (8): e33041. doi:10.1097/MD.0000000000033041. PMC 11309706. PMID 36827074.
- ^ a b c Zeng CM, Chang LL, Ying MD, Cao J, He QJ, Zhu H, Yang B (14 March 2017). "Aldo-Keto Reductase AKR1C1-AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy". Front Pharmacol. 8: 119. doi:10.3389/fphar.2017.00119. PMC 5349110. PMID 28352233.
- ^ a b c Chen WD, Zhang Y (9 March 2012). "Regulation of aldo-keto reductases in human diseases". Front Pharmacol. 3: 35. doi:10.3389/fphar.2012.00035. PMC 3297832. PMID 22408622.
- ^ Rižner TL, Lin HK, Peehl DM, Steckelbroeck S, Bauman DR, Penning TM (1 July 2003). "Human Type 3 3α-Hydroxysteroid Dehydrogenase (Aldo-Keto Reductase 1C2) and Androgen Metabolism in Prostate Cells". Endocrinology. 144 (7): 2922–2932. doi:10.1210/en.2002-0032. PMID 12810547.
- ^ Lewis MJ, Wiebe JP, Heathcote JG (2004). "Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma". BMC Cancer. 4: 27. doi:10.1186/1471-2407-4-27. PMC 459223. PMID 15212687.
- ^ "Human type 3 3alpha-hydroxysteroid dehydrogenase (Aldo-keto reductase 1C2) and androgen metabolism in prostate cells. | DrugBank Online". Archived from the original on 2024-04-17. Retrieved 2024-04-17.
- ^ Dufort I, Labrie F, Luu-The V (1 February 2001). "Human Types 1 and 3 3α-Hydroxysteroid Dehydrogenases: Differential Lability and Tissue Distribution1". The Journal of Clinical Endocrinology & Metabolism. 86 (2): 841–846. doi:10.1210/jcem.86.2.7216. PMID 11158055.
- ^ Dufort I, Labrie F, Luu-The V (February 2001). "Human types 1 and 3 3 alpha-hydroxysteroid dehydrogenases: differential lability and tissue distribution". J Clin Endocrinol Metab. 86 (2): 841–6. doi:10.1210/jcem.86.2.7216. PMID 11158055.
human types 1 and 3 3α-HSD, 20α-HSD, and type 5 17β-HSD were named AKR1C4, AKR1C2, AKR1C1, and AKR1C3, respectively
External links
1.1.1: NAD/NADP acceptor | |
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1.1.2: cytochrome acceptor | - D-lactate dehydrogenase (cytochrome)
- D-lactate dehydrogenase (cytochrome c-553)
- Mannitol dehydrogenase (cytochrome)
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1.1.3: oxygen acceptor | |
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1.1.4: disulfide as acceptor | |
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1.1.5: quinone/similar acceptor | |
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1.1.99: other acceptors | |
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Activity | |
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Regulation | |
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Classification | |
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Kinetics | |
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Types | |
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