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Target not currently curated in GtoImmuPdb
Target id: 627
Nomenclature: Progesterone receptor
Systematic Nomenclature: NR3C3
Family: 3C. 3-Ketosteroid receptors
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 933 | 11q22.1 | PGR | progesterone receptor | 43 |
| Mouse | 926 | 9 A1 | Pgr | progesterone receptor | 45 |
| Rat | 923 | 8q11 | Pgr | progesterone receptor | 29 |
| Previous and Unofficial Names |
| PGR | nuclear receptor subfamily 3 group C member 3 | progestin receptor form A | progestin receptor form B | PR | PR-A | PR-B |
| Database Links |
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| Alphafold | P06401 (Hs), Q00175 (Mm), Q63449 (Rn) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL208 (Hs), CHEMBL4969 (Mm), CHEMBL2596 (Rn) |
| DrugBank Target | P06401 (Hs) |
| Ensembl Gene | ENSG00000082175 (Hs), ENSMUSG00000031870 (Mm), ENSRNOG00000006831 (Rn) |
| Entrez Gene | 5241 (Hs), 18667 (Mm), 25154 (Rn) |
| Human Protein Atlas | ENSG00000082175 (Hs) |
| KEGG Gene | hsa:5241 (Hs), mmu:18667 (Mm), rno:25154 (Rn) |
| OMIM | 607311 (Hs) |
| Pharos | P06401 (Hs) |
| RefSeq Nucleotide | NM_000926 (Hs), NM_001202474 (Hs), NM_008829 (Mm), NM_022847 (Rn) |
| RefSeq Protein | NP_000917 (Hs), NP_001189403 (Hs), NP_032855 (Mm), NP_074038 (Rn) |
| SynPHARM |
6596 (in complex with asoprisnil) 6593 (in complex with levonorgestrel) 78983 (in complex with progesterone) 6588 (in complex with progesterone) 80081 (in complex with tanaproget) 79767 (in complex with ulipristal acetate) 79768 (in complex with ulipristal acetate) |
| UniProtKB | P06401 (Hs), Q00175 (Mm), Q63449 (Rn) |
| Wikipedia | PGR (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| progesterone |
| Rank order of potency (Human) |
| progesterone |
Download all structure-activity data for this target as a CSV file 
| Agonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| All bind in the low to high nanomolar range but reported values range widely depending on assay conditions. Although there is no specific data available for levonorgestrel, its relative affinity for progesterone receptors in MCF-7 cells is approximately 2.5 times higher than the affinity of progesterone [5]. In addition levonorgestrel is 140 times more potent than progesterone in inducing sexual behavior in rats [34]. Org 2058 has affinity similar to levonorgestrel [5]. |
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| Antagonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Binding affinity depends upon the assay and laboratory measuring it, thus the compounds are ranked in order of binding affinity using relative binding affinity (RBA). All bind in the low to high nanomolar range. Mifepristone and Asoprisnil possess tissue specific partial agonist activity [58]. EC317 was found to be a potent progesterone receptor antagonist lacking detectable PR-agonistic activity. With respect to indection of labor EC317 was far superior to RU 486. With repect to emergency contraception EC317 may be superior to CDB 2914 (Ulipristal) in both antiovulatory activity and potential desynchronizing effects in the genital tract [46]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DNA Binding |
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| DNA Binding Comments | |||||||
| Highly purified PR binds its response element with low affinity. Addition of nuclear extract or purified HMGB restores DNA binding affinity. In addition to direct response elements, PR can influence gene expression through a "tethering mechanism" independent of PR DNA binding by interacting with other DNA bound transcription factors. | |||||||
| Co-binding Partners |
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| Name | Interaction | Effect | Reference |
| Hsp90 | Physical | Cellular localization | 16,65 |
| HMGB | Physical, Functional | DNA binding | 7,48 |
| Src family kinases | Physical | Activation of rapid signaling cascades, independent of PR DNA binding. | 8 |
| TATA-binding protein | Physical | Mediates structural reorganisation of the progesterone receptor N-terminal domain to facilitate the binding of co-activators e.g. SRC-1 required for maximal transcriptional activation. | 21,35 |
| Main Co-regulators |
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| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| NCOA3 | Co-activator | Yes | Yes | No | 1,10 | |
| SRA1 | Co-activator | No | Yes | No | 36,60 | |
| NCOA1 | Co-activator | No | Yes | Yes | Steroid-receptor coactivator-1 (SRC-1) appears to be a general coactivator for steroid receptors, preferred member of the p160 family for PR | 37,39,59,61,64 |
| NCOR2 | Co-repressor | No | Yes | Yes | Nucleating platform to recruit histone deacetylase complexes. Binds in the presence of antagonist or the absence of hormone | 19,38,44,72 |
| CREBBP | Co-activator | No | Yes | No | CBP acts synergistically with steroid receptor coactivator-1 to enhance steroid receptor-dependent transcription, and binds as a multimeric complex with SRCs | 10,63 |
| JDP2 | Co-activator | Yes | Yes | No | coactivates agonist or partial agonist mediated activity through an allosteric mechanism | 73 |
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| STAT5A | Human | Activated | induced by PRB only in human breast cancer cells as detected by gene array | 52 | |
| HSD11B1 | Human | Activated | HSD11B1 (11beta-hydroxysteroid dehydrogenase) is induced by both PRA and PRB in gene array analysis of human breast cancer cells | 52 | |
| Ihh | Mouse | Activated | Indian hedgehog (Ihh) is induced in overiectomized mice 3 hours after administration of progesterone | 66 | |
| multidrug resistance 1B | Mouse | Activated | Transient transfection | observed in endometrial hyperplasia, induced by PRA only | 41 |
| SGK1 | Human | Activated | Transient transfection | SGK induced by R5020 by both PRA and PRB in human breast cancer cells. | 6,28 |
| FKBP5 | Human | Activated | Transient transfection, EMSA | Induced by PR-B, not PR-A (Tan et al. 2012). | 22,26,52,67,70 |
| TNFSF11 | Human | Activated | qRT-PCR of endogenous target gene, ChIP | 47,68 | |
| HBEGF | Human | Activated | Transient transfection, qRT-PCR of endogenous target gene | Only induced by PR-B, not PR-A. Requires Ser81, Ser294 phosphorylation inhibited by sumoylation at Lys388. Also seen in rats. | 12,23,76 |
| Main Target Genes Comments | |||||
| Another gene activated by PR is FSH-beta (follicle stimulating hormone beta), this has been demonstrated in sheep [74]. | |||||
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| Both isoforms, PR-A and B, are generally expressed at equivalent levels. PR-A:B ratios can fluctuation in endometrial tissue throughout estrus/menstrual cycle progression, and ratios also can be perturbed in breast cancer and endometriosis. Similar expression patterns are seen in rodents. | ||||||||
| Functional Assays
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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