Table 9.
Functions of proteins examined in included studies
| Gene abbreviation | Gene name (per NCBI Gene database) and function of encoded protein (link to Kyoto Encyclopedia of Genes and Genomes [KEGG] website if available)a | Gene databaseb |
|---|---|---|
| AHR | Aryl hydrocarbon receptor | https://www.ncbi.nlm.nih.gov/gene/196 |
| Regulates xenobiotic-metabolizing enzymes such as cytochrome P450. Involved in Th17 cell differentiation and Cushing syndrome https://www.genome.jp/dbget-bin/www_bget?hsa:196 Also see reference (14). |
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| Also known as RP85; bHLHe76 | ||
| AHRR | Aryl-hydrocarbon receptor repressor | https://www.ncbi.nlm.nih.gov/gene/57491 |
| Participates in aryl hydrocarbon receptor signaling cascade; involved in regulation of cell growth and differentiation. Is a feedback modulator by repressing aryl hydrocarbon receptor-dependent gene expression. KEGG webpage https://www.genome.jp/dbget-bin/www_bget?hsa:57491 Blocks activation of aryl hydrocarbon receptor signaling pathway (14). |
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| Also known as AHH; AHHR; bHLHe77 | ||
| ARNT | Aryl hydrocarbon receptor nuclear translocator | https://www.ncbi.nlm.nih.gov/gene/405 |
| Binds to ligand-bound aryl hydrocarbon receptor and aids in movement of this complex to the nucleus, where it promotes expression of genes involved in xenobiotic metabolism. Is a co-factor for transcriptional regulation by hypoxia-inducible factor 1. Implicated in Cushing syndrome and carcinogenesis https://www.genome.jp/dbget-bin/www_bget?hsa:405 Also see reference (14). |
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| Also known as HIF1B; TANGO; bHLHe2; HIF1BETA; HIF-1β; HIF1-β; HIF-1-β | ||
| COMT | Catechol-O-methyltransferase | https://www.ncbi.nlm.nih.gov/gene/1312 |
| Converts 2-hydroxyestrone to 2-methoxyestrone; converts 2-hydroxy-estradiol-17β to 2-methoxy-estradiol-17β (2.1.16) https://www.genome.jp/dbget-bin/www_bget?hsa:1312 | ||
| Also known as HEL-S-98n | ||
| CYP1A1 | cytochrome P450 family 1 subfamily A member 1 | https://www.ncbi.nlm.nih.gov/gene/1543 |
| Converts dehydroepiandrosterone to 16αhydroxyandrost-4ene-3,17-dione; converts estradiol-17β to estriol; converts estrone to 2-hydroxyestrone. (1.14.14.1) https://www.genome.jp/dbget-bin/www_bget?hsa:1543 | ||
| Also known as AHH; AHRR; CP11; CYP1; CYPIA1; P1-450; P450-C; P450DX | ||
| CYP1A2 | Cytochrome P450 family 1 subfamily A member 2 | https://www.ncbi.nlm.nih.gov/gene/1544 |
| Converts dehydroepiandronsterone to 16α-hydroxyandrost-4-ene-3,17-dione. (1.14.14.1) https://www.genome.jp/dbget-bin/www_bget?hsa:1544 Also see references (20) and (3) |
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| Also known as CP12; CYPIA2; P3-450; P450(PA) | ||
| CYP1B1 | Cytochrome P450 family 1 subfamily B member 1 | https://www.ncbi.nlm.nih.gov/gene/1545 |
| Converts estradiol-17β to 2-hydroxyestradiol-17β; (1.14.14.1) https://www.genome.jp/dbget-bin/www_bget?hsa:1545 Also see references (3, 20, 21, 23) |
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| Also known as CP1B; ASGD6; GLC3A; CYPIB1; P4501B1 | ||
| CYP2C9 | Cytochrome P450 family 2 subfamily C member 9 | https://www.ncbi.nlm.nih.gov/gene/1559 |
| This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. KEGG website https://www.genome.jp/dbget-bin/www_bget?hsa:1559 |
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| Also known as CPC9; CYP2C; CYP2C10; CYPIIC9; P450IIC9 | ||
| CYP3A4 | Cytochrome P450 family 3 subfamily A member 4 | https://www.ncbi.nlm.nih.gov/gene/1576 |
| Converts estrone to 16α-hydroxyestrone; converts dehydroepiandrosterone to 16α-hydroxyandrost-4-ene-3,17-dione; (1.14.13.32; 1.14.14.55, 1.14.14.56, 1.14.14.57, 1.14.14.73, 1.14.13.-) https://www.genome.jp/dbget-bin/www_bget?hsa:1576 Also see references (3, 20) |
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| Also known as HLP; CP33; CP34; CYP3A; NF-25; CYP3A3; P450C3; CYPIIIA3; CYPIIIA4; P450PCN1 | ||
| CYP17A1 | Cytochrome P450 family 17 subfamily A member 1 | https://www.ncbi.nlm.nih.gov/gene/1586 |
| Converts 20α-hydroxy-cholesterol to 17α,20α-dihydroxy-cholesterol; converts; converts 17α-hydroxy-pregnenolone to dehydroepiandrosterone; converts pregnenolone to 17α-hydroxy-pregnenolone; converts progesterone to 17α-hydroxy-progesterone; converts 17α-hydroxy-progesterone to androst-4-ene-3,17-dione; converts 21-deoxycortisol to 11β-hydroxy-progesterone (1.14.14.32, 1.14.14.19)) https://www.genome.jp/dbget-bin/www_bget?hsa:1586 |
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| Also known as CPT7; CYP17; S17AH; P450C17 | ||
| CYP19A1 | Cytochrome P450 family 19 subfamily A member 1 | https://www.ncbi.nlm.nih.gov/gene/1588 |
| Converts testosterone to 19-hydroxy-testosterone; converts 19-hydroxy-testosterone to 19-oxotestosterone; converts 19-oxotestosterone to estradiol-17β; converts androst-4-ene-3,17-dione to 19-hydroxyandrost-4-ene-3,17-dione; converts 19-hydroxyandrost-4-ene-3,17-dione to 19-oxoandrost-4-ene-3,17-dione; converts 19-oxoandrost-4-ene-3,17-dione to estrone (1.14.14.14) https://www.genome.jp/dbget-bin/www_bget?hsa:1588 |
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| Also known as ARO; ARO1; CPV1; CYAR; CYP19; CYPXIX; P-450AROM | ||
| ESR1 | Estrogen receptor 1 | https://www.ncbi.nlm.nih.gov/gene/2099 |
| This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Receptor to which estradiol binds, ultimately activating cascade that leads to vascular smooth muscle relaxation, influence on gene transcription involving regulation of cell cycle, apoptosis, and cell adhesion molecules https://www.genome.jp/kegg-bin/show_pathway?hsa04915 + 2099 |
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| Also known as ER; ESR; Era; ESRA; ESTRR; NR3A1 | ||
| ESR2 | Estrogen receptor 2 | https://www.ncbi.nlm.nih.gov/gene/2100 |
| This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. On binding to 17β-estradiol or related ligands, the encoded protein forms homodimers or heterodimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Receptor to which estradiol binds, ultimately activating cascade that leads to vascular smooth muscle relaxation, influence on gene transcription involving regulation of cell cycle, apoptosis, and cell adhesion molecules https://www.genome.jp/kegg-bin/show_pathway?hsa04915 + 2099 |
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| Also known as Erb; ESRB; ODG8; ESTRB; NR3A2; ER-BETA; ESR-BETA | ||
| FLT1 | Fms-related receptor tyrosine kinase 1 | https://www.ncbi.nlm.nih.gov/gene/2321 |
| This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with 7 immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. This protein binds to VEGFR-A, VEGFR-B and placental growth factor and plays an important role in angiogenesis and vasculogenesis. KEGG pathway at https://www.genome.jp/dbget-bin/www_bget?hsa:2321 Also see reference (19) |
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| Also known as FLT; FLT-1; VEGFR1; VEGFR-1 | ||
| HIFA | Hypoxia inducible factor 1 subunit α | https://www.ncbi.nlm.nih.gov/gene/3091 |
| This gene encodes the α subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed of an α and a β subunit. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Link to KEGG pathway: https://www.genome.jp/kegg-bin/show_pathway?hsa04066 + 3091 Also see reference (19) |
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| Also known as HIF1; MOP1; PASD8; HIF-1A; bHLHe78; HIF-1α; HIF1-ALPHA; HIF-1-α | ||
| HSD3B1 | Hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 | https://www.ncbi.nlm.nih.gov/gene/3283 |
| The protein encoded by this gene is an enzyme that catalyzes the oxidative conversion of delta-5-3-beta-hydroxysteroid precursors into delta-4-ketosteroids, which leads to the production of all classes of steroid hormones. The encoded protein also catalyzes the interconversion of 3-β-hydroxy- and 3-keto-5-α-androstane steroids. Link to KEGG pathway: https://www.genome.jp/kegg-bin/show_pathway?map00140 Converts 21-hydroxy-pregnenolone to 11-deoxy-corticosterone, interconverts pregnenolone and protesterone, interconverts 17α-hydroxy-progesterone and 17α-hydroxy-pregnenolone, converts 17α,21-dihydroxyo-pregnenolone to 11-deoxycortisol, converts 11β,17α,21-trihydroxy-pregnenolone to cortisol, converts dehydroepiandronaterone to androst-4-ene-3,17-dione, converts 3β,17β-dihydroxy-androst-5-ene to testosterone |
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| Also known as HSD3B; HSDB3; HSDB3A; SDR11E1; 3BETAHSD | ||
| HSD17B1 | Hydroxysteroid 17-β dehydrogenase 1 | https://www.ncbi.nlm.nih.gov/gene/3292 |
| Converts 4-androsten-11beta-ol-3,17-dione to 11β-hydroxytestosterone; Interconverts estrone to estradiol-17β; interconverts 16-α-hydroxyestrone and estriol (1.1.62) https://www.genome.jp/dbget-bin/www_bget?hsa:3292 |
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| Also known as E2DH; HSD17; EDHB17; EDH17B2; SDR28C1; 17-beta-HSD; 20-alpha-HSD | ||
| KDR | Kinase insert domain receptor | https://www.ncbi.nlm.nih.gov/gene/3791 |
| Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. This gene encodes 1 of the 2 receptors of the VEGF. This receptor, known as kinase insert domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis, and sprouting. KEGG pathway at https://www.genome.jp/kegg-bin/show_pathway?hsa04370 + 3791 Also see reference (19) |
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| Also known as FLK1; CD309; VEGFR; VEGFR2 | ||
| NRP1 | Neuropilin 1 | https://www.ncbi.nlm.nih.gov/gene/8829 |
| Neuropilins bind many ligands and various types of co-receptors; they affect cell survival, migration, and attraction. Some of the ligands and co-receptors bound by neuropilins are vascular endothelial growth factor (VEGF) and semaphorin family members. | ||
| Also known as NP1; NRP; BDCA4; CD304; VEGF165R | ||
| NRP2 | Neuropilin 2 | https://www.ncbi.nlm.nih.gov/gene/8828 |
| The encoded transmembrane protein binds to SEMA3C protein (sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C} and SEMA3F protein (sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F}, and interacts with vascular endothelial growth factor (VEGF). | ||
| Also known as NP2; NPN2; PRO2714; VEGF165R2 | ||
| NOS3 | Nitric oxide synthase 3 | https://www.ncbi.nlm.nih.gov/gene/4846 |
| Involved in estrogen signaling pathway https://www.genome.jp/dbget-bin/www_bget?hsa:4846; after estradiol binds to estrogen receptor, converts Akt (protein kinase B) to nitric oxide https://www.genome.jp/kegg-bin/show_pathway?hsa04915 + 4846 Also see reference (19) |
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| Also known as eNOS; ECNOS | ||
| Serotonin transporter gene see SLC6A4 below | Solute carrier family 6 member 4 | https://www.ncbi.nlm.nih.gov/gene/6532 |
| SLC6A4 | Solute carrier family 6 member 4 | https://www.ncbi.nlm.nih.gov/gene/6532 |
| This gene encodes an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. The encoded protein terminates the action of serotonin and recycles it in a sodium-dependent manner. This protein is a target of psychomotor stimulants, such as amphetamines and cocaine, and is a member of the sodium:neurotransmitter symporter family. KEGG pathway: https://www.genome.jp/dbget-bin/www_bget?hsa:6532 Also see reference (27) |
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| Also known as HTT; 5HTT; OCD1; SERT; 5-HTT; SERT1; hSERT; 5-HTTLPR | ||
| SULT1A1 | Sulfotransferase family 1A member 1 | https://www.ncbi.nlm.nih.gov/gene/6817 |
| Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. KEGG pathway page https://www.genome.jp/dbget-bin/www_bget?hsa:6817 Interconverts 4-hydroxyestrdaiol and 4-hydroxy-estrdaiol-sulfate; interconverts estradiol and estradiol sulfate; converts 2-hydroxyestrdaiol to 2-hydroxy-estrdaiol sulfate https://www.wikipathways.org/index.php/Pathway:WP697 |
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| Also known as PST; STP; STP1; P-PST; ST1A1; ST1A3; TSPST1; HAST1/HAST2 | ||
| SULT1E1 | Sulfotransferase family 1E member 1 | https://www.ncbi.nlm.nih.gov/gene/6783 |
| Converts estrone to estrone 3-sulfate (2.8.2.4) https://www.genome.jp/dbget-bin/www_bget?hsa:6783 |
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| Also known as EST; STE; EST-1; ST1E1 | ||
| TACR3 | Tachykinin receptor 3 | https://www.ncbi.nlm.nih.gov/gene/6870 |
| This gene encodes the receptor for the tachykinin neurokinin 3, also referred to as neurokinin B. Neurokinin B is a neuropeptide and mutations in the gene for neurokinin B are associated with normosmic hypogonadotropic hypogonadism. https://www.ncbi.nlm.nih.gov/gene/6866 | ||
| Also known as NK3; NKR; HH11; NK3R; NK-3R; TAC3R; TAC3RL | ||
| UGT1A1 | Uridine diphosphate (UDP) glucuronosyltransferase family 1 member A1 | https://www.ncbi.nlm.nih.gov/gene/54658 |
| This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. converts estradiol-17β to estradiol-17β-3-glucuronide; converts estrone to estrone glucuronide; 2-methoxyestrone to 2-methoxyestrone-3-glucuronide; converts estriol to 16-glucuronide-estriol; converts etiocholan-3α-ol-17-one to etiocholan-3α-ol-17-one 3-glucuronide; converts androsterone to androsterone-glucuronide; converts 2-methoxy-estradiol-17β to 2-methoxy-estradiol-17β-3-glucuronide; converts testosterone to testosterone glucuronide (2.4.1.117) https://www.genome.jp/kegg-bin/show_pathway?hsa00140 + 10720 |
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| Also known as GNT1; UGT1; UDPGT; UGT1A; HUG-BR1; BILIQTL1; UDPGT 1-1 | ||
| VEGFA | Vascular endothelial growth factor A | https://www.ncbi.nlm.nih.gov/gene/7422 |
| This gene is a member of the PDGF/VEGF growth factor family. It encodes a heparin-binding protein, which exists as a disulfide-linked homodimer. This growth factor induces proliferation and migration of vascular endothelial cells, and is essential both for physiological and pathological angiogenesis. KEGG signaling pathway: https://www.genome.jp/kegg-bin/show_pathway?hsa04370 + 7422 Also see reference (19) |
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| Also known as VPF; VEGF; MVCD1 | ||
| VEGFR1 see FLT1 above | Fms-related receptor tyrosine kinase 1 | https://www.ncbi.nlm.nih.gov/gene/2321 |
| VEGFR2 see KDR above | kinase insert domain receptor | https://www.ncbi.nlm.nih.gov/gene/3791 |
ahttps://www.genome.jp/kegg-bin/show_pathway?ec00140 + 2.8.2.4. If not listed in KEGG, then alternate reference for function of enzyme is cited.
bNCBI gene database at https://www.ncbi.nlm.nih.gov/gene