Progesterone receptor

Details

Name
Progesterone receptor
Synonyms
  • NR3C3
  • Nuclear receptor subfamily 3 group C member 3
  • PR
Gene Name
PGR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001112|Progesterone receptor
MTELKAKGPRAPHVAGGPPSPEVGSPLLCRPAAGPFPGSQTSDTLPEVSAIPISLDGLLF
PRPCQGQDPSDEKTQDQQSLSDVEGAYSRAEATRGAGGSSSSPPEKDSGLLDSVLDTLLA
PSGPGQSQPSPPACEVTSSWCLFGPELPEDPPAAPATQRVLSPLMSRSGCKVGDSSGTAA
AHKVLPRGLSPARQLLLPASESPHWSGAPVKPSPQAAAVEVEEEDGSESEESAGPLLKGK
PRALGGAAAGGGAAAVPPGAAAGGVALVPKEDSRFSAPRVALVEQDAPMAPGRSPLATTV
MDFIHVPILPLNHALLAARTRQLLEDESYDGGAGAASAFAPPRSSPCASSTPVAVGDFPD
CAYPPDAEPKDDAYPLYSDFQPPALKIKEEEEGAEASARSPRSYLVAGANPAAFPDFPLG
PPPPLPPRATPSRPGEAAVTAAPASASVSSASSSGSTLECILYKAEGAPPQQGPFAPPPC
KAPGASGCLLPRDGLPSTSASAAAAGAAPALYPALGLNGLPQLGYQAAVLKEGLPQVYPP
YLNYLRPDSEASQSPQYSFESLPQKICLICGDEASGCHYGVLTCGSCKVFFKRAMEGQHN
YLCAGRNDCIVDKIRRKNCPACRLRKCCQAGMVLGGRKFKKFNKVRVVRALDAVALPQPV
GVPNESQALSQRFTFSPGQDIQLIPPLINLLMSIEPDVIYAGHDNTKPDTSSSLLTSLNQ
LGERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGWRSYKHVSGQMLYFAP
DLILNEQRMKESSFYSLCLTMWQIPQEFVKLQVSQEEFLCMKVLLLLNTIPLEGLRSQTQ
FEEMRSSYIRELIKAIGLRQKGVVSSSQRFYQLTKLLDNLHDLVKQLHLYCLNTFIQSRA
LSVEFPEMMSEVIAAQLPKILAGMVKPLLFHKK
Number of residues
933
Molecular Weight
98979.96
Theoretical pI
6.45
GO Classification
Functions
ATPase binding / DNA binding / enzyme binding / receptor binding / RNA polymerase II core promoter proximal region sequence-specific DNA binding / RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding / steroid binding / steroid hormone receptor activity / transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding / zinc ion binding
Processes
cell-cell signaling / epithelial cell maturation / gene expression / lung alveolus development / negative regulation of gene expression / ovulation from ovarian follicle / paracrine signaling / positive regulation of transcription from RNA polymerase II promoter / progesterone receptor signaling pathway / regulation of epithelial cell proliferation / signal transduction / tertiary branching involved in mammary gland duct morphogenesis / transcription initiation from RNA polymerase II promoter
Components
mitochondrial outer membrane / nucleoplasm
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0010387|Progesterone receptor (PGR)
ATGACTGAGCTGAAGGCAAAGGGTCCCCGGGCTCCCCACGTGGCGGGCGGCCCGCCCTCC
CCCGAGGTCGGATCCCCACTGCTGTGTCGCCCAGCCGCAGGTCCGTTCCCGGGGAGCCAG
ACCTCGGACACCTTGCCTGAAGTTTCGGCCATACCTATCTCCCTGGACGGGCTACTCTTC
CCTCGGCCCTGCCAGGGACAGGACCCCTCCGACGAAAAGACGCAGGACCAGCAGTCGCTG
TCGGACGTGGAGGGCGCATATTCCAGAGCTGAAGCTACAAGGGGTGCTGGAGGCAGCAGT
TCTAGTCCCCCAGAAAAGGACAGCGGACTGCTGGACAGTGTCTTGGACACTCTGTTGGCG
CCCTCAGGTCCCGGGCAGAGCCAACCCAGCCCTCCCGCCTGCGAGGTCACCAGCTCTTGG
TGCCTGTTTGGCCCCGAACTTCCCGAAGATCCACCGGCTGCCCCCGCCACCCAGCGGGTG
TTGTCCCCGCTCATGAGCCGGTCCGGGTGCAAGGTTGGAGACAGCTCCGGGACGGCAGCT
GCCCATAAAGTGCTGCCCCGGGGCCTGTCACCAGCCCGGCAGCTGCTGCTCCCGGCCTCT
GAGAGCCCTCACTGGTCCGGGGCCCCAGTGAAGCCGTCTCCGCAGGCCGCTGCGGTGGAG
GTTGAGGAGGAGGATGGCTCTGAGTCCGAGGAGTCTGCGGGTCCGCTTCTGAAGGGCAAA
CCTCGGGCTCTGGGTGGCGCGGCGGCTGGAGGAGGAGCCGCGGCTGTCCCGCCGGGGGCG
GCAGCAGGAGGCGTCGCCCTGGTCCCCAAGGAAGATTCCCGCTTCTCAGCGCCCAGGGTC
GCCCTGGTGGAGCAGGACGCGCCGATGGCGCCCGGGCGCTCCCCGCTGGCCACCACGGTG
ATGGATTTCATCCACGTGCCTATCCTGCCTCTCAATCACGCCTTATTGGCAGCCCGCACT
CGGCAGCTGCTGGAAGACGAAAGTTACGACGGCGGGGCCGGGGCTGCCAGCGCCTTTGCC
CCGCCGCGGAGTTCACCCTGTGCCTCGTCCACCCCGGTCGCTGTAGGCGACTTCCCCGAC
TGCGCGTACCCGCCCGACGCCGAGCCCAAGGACGACGCGTACCCTCTCTATAGCGACTTC
CAGCCGCCCGCTCTAAAGATAAAGGAGGAGGAGGAAGGCGCGGAGGCCTCCGCGCGCTCC
CCGCGTTCCTACCTTGTGGCCGGTGCCAACCCCGCAGCCTTCCCGGATTTCCCGTTGGGG
CCACCGCCCCCGCTGCCGCCGCGAGCGACCCCATCCAGACCCGGGGAAGCGGCGGTGACG
GCCGCACCCGCCAGTGCCTCAGTCTCGTCTGCGTCCTCCTCGGGGTCGACCCTGGAGTGC
ATCCTGTACAAAGCGGAGGGCGCGCCGCCCCAGCAGGGCCCGTTCGCGCCGCCGCCCTGC
AAGGCGCCGGGCGCGAGCGGCTGCCTGCTCCCGCGGGACGGCCTGCCCTCCACCTCCGCC
TCTGCCGCCGCCGCCGGGGCGGCCCCCGCGCTCTACCCTGCACTCGGCCTCAACGGGCTC
CCGCAGCTCGGCTACCAGGCCGCCGTGCTCAAGGAGGGCCTGCCGCAGGTCTACCCGCCC
TATCTCAACTACCTGAGGCCGGATTCAGAAGCCAGCCAGAGCCCACAATACAGCTTCGAG
TCATTACCTCAGAAGATTTGTTTAATCTGTGGGGATGAAGCATCAGGCTGTCATTATGGT
GTCCTTACCTGTGGGAGCTGTAAGGTCTTCTTTAAGAGGGCAATGGAAGGGCAGCACAAC
TACTTATGTGCTGGAAGAAATGACTGCATCGTTGATAAAATCCGCAGAAAAAACTGCCCA
GCATGTCGCCTTAGAAAGTGCTGTCAGGCTGGCATGGTCCTTGGAGGTCGAAAATTTAAA
AAGTTCAATAAAGTCAGAGTTGTGAGAGCACTGGATGCTGTTGCTCTCCCACAGCCAGTG
GGCGTTCCAAATGAAAGCCAAGCCCTAAGCCAGAGATTCACTTTTTCACCAGGTCAAGAC
ATACAGTTGATTCCACCACTGATCAACCTGTTAATGAGCATTGAACCAGATGTGATCTAT
GCAGGACATGACAACACAAAACCTGACACCTCCAGTTCTTTGCTGACAAGTCTTAATCAA
CTAGGCGAGAGGCAACTTCTTTCAGTAGTCAAGTGGTCTAAATCATTGCCAGGTTTTCGA
AACTTACATATTGATGACCAGATAACTCTCATTCAGTATTCTTGGATGAGCTTAATGGTG
TTTGGTCTAGGATGGAGATCCTACAAACACGTCAGTGGGCAGATGCTGTATTTTGCACCT
GATCTAATACTAAATGAACAGCGGATGAAAGAATCATCATTCTATTCATTATGCCTTACC
ATGTGGCAGATCCCACAGGAGTTTGTCAAGCTTCAAGTTAGCCAAGAAGAGTTCCTCTGT
ATGAAAGTATTGTTACTTCTTAATACAATTCCTTTGGAAGGGCTACGAAGTCAAACCCAG
TTTGAGGAGATGAGGTCAAGCTACATTAGAGAGCTCATCAAGGCAATTGGTTTGAGGCAA
AAAGGAGTTGTGTCGAGCTCACAGCGTTTCTATCAACTTACAAAACTTCTTGATAACTTG
CATGATCTTGTCAAACAACTTCATCTGTACTGCTTGAATACATTTATCCAGTCCCGGGCA
CTGAGTGTTGAATTTCCAGAAATGATGTCTGAAGTTATTGCTGCACAATTACCCAAGATA
TTGGCAGGGATGGTGAAACCCCTTCTCTTTCATAAAAAGTGA
Chromosome Location
11
Locus
11q22-q23
External Identifiers
ResourceLink
UniProtKB IDP06401
UniProtKB Entry NamePRGR_HUMAN
GenBank Protein ID35652
GenBank Gene IDX51730
GenAtlas IDPGR
HGNC IDHGNC:8910
General References
  1. Kastner P, Krust A, Turcotte B, Stropp U, Tora L, Gronemeyer H, Chambon P: Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J. 1990 May;9(5):1603-14. [PubMed:2328727]
  2. Misrahi M, Atger M, d'Auriol L, Loosfelt H, Meriel C, Fridlansky F, Guiochon-Mantel A, Galibert F, Milgrom E: Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA. Biochem Biophys Res Commun. 1987 Mar 13;143(2):740-8. [PubMed:3551956]
  3. Chen C, Opazo JC, Erez O, Uddin M, Santolaya-Forgas J, Goodman M, Grossman LI, Romero R, Wildman DE: The human progesterone receptor shows evidence of adaptive evolution associated with its ability to act as a transcription factor. Mol Phylogenet Evol. 2008 May;47(2):637-49. doi: 10.1016/j.ympev.2007.12.026. Epub 2008 Feb 1. [PubMed:18375150]
  4. Saner KJ, Welter BH, Zhang F, Hansen E, Dupont B, Wei Y, Price TM: Cloning and expression of a novel, truncated, progesterone receptor. Mol Cell Endocrinol. 2003 Feb 28;200(1-2):155-63. [PubMed:12644308]
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  6. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [PubMed:16554811]
  7. Knotts TA, Orkiszewski RS, Cook RG, Edwards DP, Weigel NL: Identification of a phosphorylation site in the hinge region of the human progesterone receptor and additional amino-terminal phosphorylation sites. J Biol Chem. 2001 Mar 16;276(11):8475-83. Epub 2000 Dec 7. [PubMed:11110801]
  8. Dai Q, Shah AA, Garde RV, Yonish BA, Zhang L, Medvitz NA, Miller SE, Hansen EL, Dunn CN, Price TM: A truncated progesterone receptor (PR-M) localizes to the mitochondrion and controls cellular respiration. Mol Endocrinol. 2013 May;27(5):741-53. doi: 10.1210/me.2012-1292. Epub 2013 Mar 21. [PubMed:23518922]
  9. Zhang Y, Beck CA, Poletti A, Edwards DP, Weigel NL: Identification of a group of Ser-Pro motif hormone-inducible phosphorylation sites in the human progesterone receptor. Mol Endocrinol. 1995 Aug;9(8):1029-40. [PubMed:7476977]
  10. Beck CA, Zhang Y, Altmann M, Weigel NL, Edwards DP: Stoichiometry and site-specific phosphorylation of human progesterone receptor in native target cells and in the baculovirus expression system. J Biol Chem. 1996 Aug 9;271(32):19546-55. [PubMed:8702648]
  11. Zhang Y, Beck CA, Poletti A, Clement JP 4th, Prendergast P, Yip TT, Hutchens TW, Edwards DP, Weigel NL: Phosphorylation of human progesterone receptor by cyclin-dependent kinase 2 on three sites that are authentic basal phosphorylation sites in vivo. Mol Endocrinol. 1997 Jun;11(6):823-32. [PubMed:9171245]
  12. Clemm DL, Sherman L, Boonyaratanakornkit V, Schrader WT, Weigel NL, Edwards DP: Differential hormone-dependent phosphorylation of progesterone receptor A and B forms revealed by a phosphoserine site-specific monoclonal antibody. Mol Endocrinol. 2000 Jan;14(1):52-65. [PubMed:10628747]
  13. Lange CA, Shen T, Horwitz KB: Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome. Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1032-7. [PubMed:10655479]
  14. Qi C, Chang J, Zhu Y, Yeldandi AV, Rao SM, Zhu YJ: Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha. J Biol Chem. 2002 Aug 9;277(32):28624-30. Epub 2002 May 30. [PubMed:12039952]
  15. Hsiao PW, Fryer CJ, Trotter KW, Wang W, Archer TK: BAF60a mediates critical interactions between nuclear receptors and the BRG1 chromatin-remodeling complex for transactivation. Mol Cell Biol. 2003 Sep;23(17):6210-20. [PubMed:12917342]
  16. Pierson-Mullany LK, Lange CA: Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Mol Cell Biol. 2004 Dec;24(24):10542-57. [PubMed:15572662]
  17. Narayanan R, Edwards DP, Weigel NL: Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity. Mol Cell Biol. 2005 Apr;25(8):2885-98. [PubMed:15798179]
  18. Chadli A, Graham JD, Abel MG, Jackson TA, Gordon DF, Wood WM, Felts SJ, Horwitz KB, Toft D: GCUNC-45 is a novel regulator for the progesterone receptor/hsp90 chaperoning pathway. Mol Cell Biol. 2006 Mar;26(5):1722-30. [PubMed:16478993]
  19. Man JH, Li HY, Zhang PJ, Zhou T, He K, Pan X, Liang B, Li AL, Zhao J, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM: PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus. Nucleic Acids Res. 2006;34(19):5552-66. Epub 2006 Oct 4. [PubMed:17020914]
  20. Zhang PJ, Zhao J, Li HY, Man JH, He K, Zhou T, Pan X, Li AL, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM: CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. EMBO J. 2007 Apr 4;26(7):1831-42. Epub 2007 Mar 8. [PubMed:17347654]
  21. Daniel AR, Faivre EJ, Lange CA: Phosphorylation-dependent antagonism of sumoylation derepresses progesterone receptor action in breast cancer cells. Mol Endocrinol. 2007 Dec;21(12):2890-906. Epub 2007 Aug 23. [PubMed:17717077]
  22. Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA: Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids. 2007 Feb;72(2):188-201. Epub 2006 Dec 14. [PubMed:17173941]
  23. Faivre EJ, Daniel AR, Hillard CJ, Lange CA: Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008 Apr;22(4):823-37. doi: 10.1210/me.2007-0437. Epub 2008 Jan 17. [PubMed:18202149]
  24. Pedram A, Razandi M, Deschenes RJ, Levin ER: DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors. Mol Biol Cell. 2012 Jan;23(1):188-99. doi: 10.1091/mbc.E11-07-0638. Epub 2011 Oct 26. [PubMed:22031296]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00304DesogestrelapprovedyesagonistDetails
DB00351Megestrol acetateapproved, investigational, vet_approvedyesagonistDetails
DB00367Levonorgestrelapproved, investigationalyesmodulatorDetails
DB00378Dydrogesteroneapproved, investigational, withdrawnyesagonistDetails
DB00396Progesteroneapproved, vet_approvedyesagonistDetails
DB00603Medroxyprogesterone acetateapproved, investigationalyesagonistDetails
DB00717NorethisteroneapprovedunknownagonistDetails
DB00834Mifepristoneapproved, investigationalyesantagonistDetails
DB00957Norgestimateapproved, investigationalyesagonistDetails
DB00294Etonogestrelapproved, investigationalyesagonistDetails
DB00823Ethynodiol diacetateapprovedyesagonistDetails
DB01395DrospirenoneapprovedyesagonistDetails
DB02998MetriboloneexperimentalunknownDetails
DB05253Telapristone acetateinvestigationalunknownDetails
DB04787TanaprogetinvestigationalyesagonistDetails
DB06680AsoprisnilinvestigationalunknownDetails
DB01406DanazolapprovedyesagonistDetails
DB01431AllylestrenolexperimentalyesagonistDetails
DB00588Fluticasone propionateapprovedunknownagonistDetails
DB06713Norelgestrominapproved, investigationalyesagonistDetails
DB08867UlipristalapprovedyesmodulatorDetails
DB00421SpironolactoneapprovedunknownagonistDetails
DB06789Hydroxyprogesterone caproateapproved, investigationalunknownagonistDetails
DB09389NorgestrelapprovedyesbinderDetails
DB00431Lindaneapproved, withdrawnunknownDetails
DB00648MitotaneapprovedunknownDetails
DB02746Phthalic AcidexperimentalunknownDetails
DB00764Mometasoneapproved, vet_approvedunknownagonistDetails
DB11219EnzacameneapprovedunknownantagonistDetails
DB11064Homosalateapproved, investigationalunknownantagonistDetails
DB01428Oxybenzoneapproved, investigationalunknownantagonistDetails
DB06730GestodeneinvestigationalyesbinderactivatorDetails
DB09123DienogestapprovedyesagonistDetails
DB09124MedrogestoneapprovedyesligandDetails
DB11619GestrinoneapprovedunknownantagonistagonistDetails
DB13857DemegestoneexperimentalyesagonistDetails
DB14512Mometasone furoateapproved, investigational, vet_approvedunknownDetails
DB14583Segesterone acetateapproved, experimental, investigationalyesagonistactivatorDetails
DB13867Fluticasoneapproved, experimentalunknownagonistDetails
DB08906Fluticasone furoateapprovedunknownagonistDetails