Summary: Androgen receptor
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "Androgen receptor". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at firstname.lastname@example.org and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Androgen receptor Edit Wikipedia article
Structure of the ligand binding domain of the androgen receptor (rainbow cartoon) complexed with testosterone (white sticks).
|Symbols||; AIS; AR8; DHTR; HUMARA; HYSP1; KD; NR3C4; SBMA; SMAX1; TFM|
|External IDs||IUPHAR: ChEMBL: GeneCards:|
|RNA expression pattern|
crystal structure of the human androgen receptor ligand binding domain bound with an androgen receptor nh2-terminal peptide, ar20-30, and r1881
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding either of the androgenic hormones, testosterone, or dihydrotestosterone  in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.
The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression; however, the androgen receptor has other functions as well. Androgen regulated genes are critical for the development and maintenance of the male sexual phenotype.
- 1 Function
- 2 Genetics
- 3 Structure
- 4 As a drug target
- 5 Interactions
- 6 See also
- 7 References
- 8 External links
Effect on development
In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha-reductase to dihydrotestosterone, an even more potent agonist for androgen receptor activation. Testosterone appears to be the primary androgen receptor-activating hormone in the Wolffian duct, whereas dihydrotestosterone is the main androgenic hormone in the urogenital sinus, urogenital tubercle, and hair follicles. Hence, testosterone is responsible primarily for the development of male primary sexual characteristics, whereas dihydrotestosterone is responsible for secondary male characteristics.
Androgens cause slow epiphysis, or maturation of the bones, but more of the potent epiphysis effect comes from the estrogen produced by aromatization of androgens. Steroid users of teen age may find that their growth had been stunted by androgen and/or estrogen excess. People with too little sex hormones can be short during puberty but end up taller as adults as in androgen insensitivity syndrome or estrogen insensitivity syndrome.
Also, AR knockout-mice studies have shown that AR is essential for normal female fertility, being required for development and full functionality of the ovarian follicles and ovulation, working through both intra-ovarian and neuroendocrine mechanisms.
Maintenance of male skeletal integrity
Via the Androgen receptor, androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling can be attributed to both osteoblasts and osteocytes.
Mechanism of action
The primary mechanism of action for androgen receptors is direct regulation of gene transcription. The binding of an androgen to the androgen receptor results in a conformational change in the receptor that, in turn, causes dissociation of heat shock proteins, transport from the cytosol into the cell nucleus, and dimerization. The androgen receptor dimer binds to a specific sequence of DNA known as a hormone response element. Androgen receptors interact with other proteins in the nucleus, resulting in up- or down-regulation of specific gene transcription. Up-regulation or activation of transcription results in increased synthesis of messenger RNA, which, in turn, is translated by ribosomes to produce specific proteins. One of the known target genes of androgen receptor activation is the insulin-like growth factor I receptor (IGF-1R). Thus, changes in levels of specific proteins in cells is one way that androgen receptors control cell behavior.
One function of androgen receptor that is independent of direct binding to its target DNA sequence, is facilitated by recruitment via other DNA-binding proteins. One example is serum response factor, a protein that activates several genes that cause muscle growth.
Androgen receptor is modified by acetylation, which directly promotes contact independent growth of prostate cancer cells.
More recently, androgen receptors have been shown to have a second mode of action. As has been also found for other steroid hormone receptors such as estrogen receptors, androgen receptors can have actions that are independent of their interactions with DNA. Androgen receptors interact with certain signal transduction proteins in the cytoplasm. Androgen binding to cytoplasmic androgen receptors can cause rapid changes in cell function independent of changes in gene transcription, such as changes in ion transport. Regulation of signal transduction pathways by cytoplasmic androgen receptors can indirectly lead to changes in gene transcription, for example, by leading to phosphorylation of other transcription factors.
The androgen insensitivity syndrome, formerly known as testicular feminization, is caused by a mutation of the androgen receptor gene located on the X chromosome (locus:Xq11-Xq12). The androgen receptor seems to affect neuron physiology and is defective in Kennedy's disease. In addition, point mutations and trinucleotide repeat polymorphisms has been linked to a number of additional disorders.
- AR-A - 87 kDa - N-terminus truncated (lacks the first 187 amino acids), which results from in vitro proteolysis.
- AR-B - 110 kDa - full length
- A/B) - N-terminal regulatory domain contains:
- activation function 1 (AF-1) between residues 101 and 370 required for full ligand activated transcriptional activity
- activation function 5 (AF-5) between residues 360-485 is responsible for the constitutive activity (activity without bound ligand)
- dimerization surface involving residues 1-36 (containing the FXXLF motif where F = phenylalanine, L = leucine, and X = any amino acid residue) and 370-494, both of which interact with the LBD in an intramolecular head-to-tail interaction
- C) - DNA binding domain (DBD)
- D) - Hinge region - flexible region that connects the DBD with the LBD; along with the DBD, contains a ligand dependent nuclear localization signal
- E) - Ligand binding domain (LBD) containing
- F) - C-terminal domain
As a drug target
AR antagonists: flutamide, nilutamide, bicalutamide, enzalutamide, apalutamide, cyproterone acetate, megestrol acetate, chlormadinone acetate, spironolactone, canrenone, drospirenone, ketoconazole, topilutamide (fluridil), cimetidine.
Androgen receptor has been shown to interact with:
- Calmodulin 1,
- Caveolin 1,
- CREB-binding protein,
- Cyclin D1,
- Cyclin-dependent kinase 7,
- Death associated protein 6,
- Epidermal growth factor receptor,
- Retinoblastoma protein,
- Small heterodimer partner,
- Testicular receptor 2,
- Testicular receptor 4,
- UXT, and
- "Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity". Protein Sci. 15 (5): 987–99. doi:10.1110/ps.051905906. PMC 2242507. PMID 16641486.; Pereira de Jésus-Tran K, Côté PL, Cantin L, Blanchet J, Labrie F, Breton R (May 2006).
- Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS (June 1995). "Androgen receptor defects: historical, clinical, and molecular perspectives". Endocr. Rev. 16 (3): 271–321. doi:10.1210/edrv-16-3-271. PMID 7671849.
- Gottlieb B, Lombroso R, Beitel LK, Trifiro MA (January 2005). "Molecular pathology of the androgen receptor in male (in)fertility". Reprod. Biomed. Online 10 (1): 42–8. doi:10.1016/S1472-6483(10)60802-4. PMID 15705293.
- Choong CS, Wilson EM (December 1998). "Trinucleotide repeats in the human androgen receptor: a molecular basis for disease". J. Mol. Endocrinol. 21 (3): 235–57. doi:10.1677/jme.0.0210235. PMID 9845666.
- Meehan KL, Sadar MD (May 2003). "Androgens and androgen receptor in prostate and ovarian malignancies". Front. Biosci. 8 (1-3): d780–800. doi:10.2741/1063. PMID 12700055.
- Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, Hochberg RB, McKay L, Renoir JM, Weigel NL, Wilson EM, McDonnell DP, Cidlowski JA (December 2006). "International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors". Pharmacol. Rev. 58 (4): 782–97. doi:10.1124/pr.58.4.9. PMID 17132855.
- Roy AK, Lavrovsky Y, Song CS, Chen S, Jung MH, Velu NK, Bi BY, Chatterjee B (1999). "Regulation of androgen action". Vitam. Horm. Vitamins & Hormones 55: 309–52. doi:10.1016/S0083-6729(08)60938-3. ISBN 978-0-12-709855-5. PMID 9949684.
- Bardin CW, Brown T, Isomaa VV, Jänne OA (1983). "Progestins can mimic, inhibit and potentiate the actions of androgens". Pharmacol. Ther. 23 (3): 443–59. doi:10.1016/0163-7258(83)90023-2. PMID 6371845.
- Raudrant D, Rabe T (2003). "Progestogens with antiandrogenic properties". Drugs 63 (5): 463–92. doi:10.2165/00003495-200363050-00003. PMID 12600226.
- Mooradian AD, Morley JE, Korenman SG (1987). "Biological actions of androgens". Endocr. Rev. 8 (1): 1–28. doi:10.1210/edrv-8-1-1. PMID 3549275.
- Heinlein CA, Chang C (2002). "The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions". Mol. Endocrinol. 16 (10): 2181–7. doi:10.1210/me.2002-0070. PMID 12351684.
- Davison SL, Bell R (April 2006). "Androgen physiology". Semin. Reprod. Med. 24 (2): 71–7. doi:10.1055/s-2006-939565. PMID 16633980.
- Sinisi AA, Pasquali D, Notaro A, Bellastella A (2003). "Sexual differentiation". J. Endocrinol. Invest. 26 (3 Suppl): 23–8. PMID 12834017.
- Frank GR (September 2003). "Role of estrogen and androgen in pubertal skeletal physiology". Med. Pediatr. Oncol. 41 (3): 217–21. doi:10.1002/mpo.10340. PMID 12868122.
- Walters KA, Simanainen U, Handelsman DJ (March 2010). "Molecular insights into androgen actions in male and female reproductive function from androgen receptor knockout models". Hum Reprod Update 16 (5): 543–58. doi:10.1093/humupd/dmq003. PMID 20231167.
- Sinnesael M., Claessens F., Laurent M., Dubois V., Boonen S., Deboel L., Vanderschueren D. (Dec 2012). "Androgen receptor (AR) in osteocytes is important for the maintenance of male skeletal integrity: evidence from targeted AR disruption in mouse osteocytes". Journal of Bone and Mineral Research 27 (12): 2535–43. doi:10.1002/jbmr.1713. PMID 22836391.
- Heemers HV, Tindall DJ (December 2007). "Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex". Endocr. Rev. 28 (7): 778–808. doi:10.1210/er.2007-0019. PMID 17940184.
- Pandini G, Mineo R, Frasca F, Roberts CT Jr, Marcelli M, Vigneri R, Belfiore A (March 2005). "Androgens up-regulate the insulin-like growth factor-I receptor in prostate cancer cells". Cancer Res. 65 (5): 1849–57. doi:10.1158/0008-5472.CAN-04-1837. PMID 15753383.
- Vlahopoulos S, Zimmer WE, Jenster G, Belaguli NS, Balk SP, Brinkmann AO, Lanz RB, Zoumpourlis VC, Schwartz RJ (2005). "Recruitment of the androgen receptor via serum response factor facilitates expression of a myogenic gene". J. Biol. Chem. 280 (9): 7786–92. doi:10.1074/jbc.M413992200. PMID 15623502.
- Fu M, Wang C, Reutens AT, Wang J, Angeletti RH, Siconolfi-Baez L, Ogryzko V, Avantaggiati ML, Pestell RG (July 2000). "p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation". J. Biol. Chem. 275 (27): 20853–60. doi:10.1074/jbc.M000660200. PMID 10779504.
- Fix C, Jordan C, Cano P, Walker WH (2004). "Testosterone activates mitogen-activated protein kinase and the cAMP response element binding protein transcription factor in Sertoli cells". Proc Natl Acad Sci USA 101 (30): 10919–24. doi:10.1073/pnas.0404278101. PMC 503720. PMID 15263086.
- Chang CS, Kokontis J, Liao ST (1988). "Molecular cloning of human and rat complementary DNA encoding androgen receptors". Science 240 (4850): 324–6. doi:10.1126/science.3353726. PMID 3353726.
- Trapman J, Klaassen P, Kuiper GG, van der Korput JA, Faber PW, van Rooij HC, Geurts van Kessel A, Voorhorst MM, Mulder E, Brinkmann AO (1988). "Cloning, structure and expression of a cDNA encoding the human androgen receptor". Biochem. Biophys. Res. Commun. 153 (1): 241–8. doi:10.1016/S0006-291X(88)81214-2. PMID 3377788.
- Brown TR (1995). "Human androgen insensitivity syndrome" (abstract). J. Androl. 16 (4): 299–303. PMID 8537246.
- Kennedy WR, Alter M, Sung JH (1968). "Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait". Neurology 18 (7): 671–80. doi:10.1212/WNL.18.7.671. PMID 4233749.
- Yu Z, Dadgar N, Albertelli M, Gruis K, Jordan C, Robins DM, Lieberman AP (2006). "Androgen-dependent pathology demonstrates myopathic contribution to the Kennedy disease phenotype in a mouse knock-in model". J. Clin. Invest. 116 (10): 2663–72. doi:10.1172/JCI28773. PMC 1564432. PMID 16981011.
- Rajender S, Singh L, Thangaraj K (2007). "Phenotypic heterogeneity of mutations in androgen receptor gene". Asian J. Androl. 9 (2): 147–79. doi:10.1111/j.1745-7262.2007.00250.x. PMID 17334586.
- Wilson CM, McPhaul MJ (1994). "A and B forms of the androgen receptor are present in human genital skin fibroblasts". Proc. Natl. Acad. Sci. U.S.A. 91 (4): 1234–8. doi:10.1073/pnas.91.4.1234. PMC 43131. PMID 8108393.
- Gregory CW, He B, Wilson EM. (2001). "The putative androgen receptor-A form results from in vitro proteolysis". J Mol Endocrinol 27 (3): 309–19. doi:10.1677/jme.0.0270309. PMID 11719283.
- Brinkmann AO, Klaasen P, Kuiper GG, van der Korput JA, Bolt J, de Boer W, Smit A, Faber PW, van Rooij HC, Geurts van Kessel A, Voorhorst MM, Mulder E, Trapman J (1989). "Structure and function of the androgen receptor". Urol. Res. 17 (2): 87–93. doi:10.1007/BF00262026. PMID 2734982.
- Jenster G, van der Korput HA, Trapman J, Brinkmann AO (1995). "Identification of two transcription activation units in the N-terminal domain of the human androgen receptor". J. Biol. Chem. 270 (13): 7341–6. doi:10.1074/jbc.270.13.7341. PMID 7706276.
- Schaufele F, Carbonell X, Guerbadot M, Borngraeber S, Chapman MS, Ma AA, Miner JN, Diamond MI (July 2005). "The structural basis of androgen receptor activation: Intramolecular and intermolecular amino–carboxy interactions". Proc. Natl. Acad. Sci. U.S.A. 102 (28): 9802–7. doi:10.1073/pnas.0408819102. PMC 1168953. PMID 15994236.
- Klokk TI, Kurys P, Elbi C, Nagaich AK, Hendarwanto A, Slagsvold T, Chang CY, Hager GL, Saatcioglu F (March 2007). "Ligand-Specific Dynamics of the Androgen Receptor at Its Response Element in Living Cells". Mol. Cell. Biol. 27 (5): 1823–43. doi:10.1128/MCB.01297-06. PMC 1820481. PMID 17189428.
- van Royen ME, Cunha SM, Brink MC, Mattern KA, Nigg AL, Dubbink HJ, Verschure PJ, Trapman J, Houtsmuller AB (April 2007). "Compartmentalization of androgen receptor protein–protein interactions in living cells". J. Cell Biol. 177 (1): 63–72. doi:10.1083/jcb.200609178. PMC 2064112. PMID 17420290.
- Langley E, Zhou ZX, Wilson EM (1995). "Evidence for an anti-parallel orientation of the ligand-activated human androgen receptor dimer". J. Biol. Chem. 270 (50): 29983–90. doi:10.1074/jbc.270.50.29983. PMID 8530400.
- Berrevoets CA, Doesburg P, Steketee K, Trapman J, Brinkmann AO (1998). "Functional interactions of the AF-2 activation domain core region of the human androgen receptor with the amino-terminal domain and with the transcriptional coactivator TIF2 (transcriptional intermediary factor2)". Mol. Endocrinol. 12 (8): 1172–83. doi:10.1210/me.12.8.1172. PMID 9717843.
- Dubbink HJ, Hersmus R, Verma CS, van der Korput HA, Berrevoets CA, van Tol J, Ziel-van der Made AC, Brinkmann AO, Pike AC, Trapman J (2004). "Distinct recognition modes of FXXLF and LXXLL motifs by the androgen receptor". Mol. Endocrinol. 18 (9): 2132–50. doi:10.1210/me.2003-0375. PMID 15178743.
- Kaku N, Matsuda KI, Tsujimura A, Kawata M (April 2008). "Characterization of Nuclear Import of the Domain-Specific Androgen Receptor in Association with the Importin α/β and Ran-Guanosine 5′-Triphosphate Systems". Endocrinology 149 (8): 3960–9. doi:10.1210/en.2008-0137. PMC 2488236. PMID 18420738.
- Saporita AJ, Zhang Q, Navai N, Dincer Z, Hahn J, Cai X, Wang Z (October 2003). "Identification and characterization of a ligand-regulated nuclear export signal in androgen receptor". J. Biol. Chem. 278 (43): 41998–2005. doi:10.1074/jbc.M302460200. PMID 12923188.
- Lin HK, Yeh S, Kang HY, Chang C (June 2001). "Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor". Proc. Natl. Acad. Sci. U.S.A. 98 (13): 7200–5. doi:10.1073/pnas.121173298. PMC 34646. PMID 11404460.
- Shatkina L, Mink S, Rogatsch H, Klocker H, Langer G, Nestl A, Cato AC (October 2003). "The Cochaperone Bag-1L Enhances Androgen Receptor Action via Interaction with the NH2-Terminal Region of the Receptor". Mol. Cell. Biol. 23 (20): 7189–97. doi:10.1128/MCB.23.20.7189-7197.2003. PMC 230325. PMID 14517289.
- Knee DA, Froesch BA, Nuber U, Takayama S, Reed JC (April 2001). "Structure-function analysis of Bag1 proteins. Effects on androgen receptor transcriptional activity". J. Biol. Chem. 276 (16): 12718–24. doi:10.1074/jbc.M010841200. PMID 11278763.
- Froesch BA, Takayama S, Reed JC (May 1998). "BAG-1L protein enhances androgen receptor function". J. Biol. Chem. 273 (19): 11660–6. doi:10.1074/jbc.273.19.11660. PMID 9565586.
- Song LN, Coghlan M, Gelmann EP (January 2004). "Antiandrogen effects of mifepristone on coactivator and corepressor interactions with the androgen receptor". Mol. Endocrinol. 18 (1): 70–85. doi:10.1210/me.2003-0189. PMID 14593076.
- Masiello D, Chen SY, Xu Y, Verhoeven MC, Choi E, Hollenberg AN, Balk SP (October 2004). "Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells". Mol. Endocrinol. 18 (10): 2388–401. doi:10.1210/me.2003-0436. PMID 15256534.
- Yang F, Li X, Sharma M, Sasaki CY, Longo DL, Lim B, Sun Z (March 2002). "Linking beta-catenin to androgen-signaling pathway". J. Biol. Chem. 277 (13): 11336–44. doi:10.1074/jbc.M111962200. PMID 11792709.
- Amir AL, Barua M, McKnight NC, Cheng S, Yuan X, Balk SP (August 2003). "A direct beta-catenin-independent interaction between androgen receptor and T cell factor 4". J. Biol. Chem. 278 (33): 30828–34. doi:10.1074/jbc.M301208200. PMID 12799378.
- Mulholland DJ, Read JT, Rennie PS, Cox ME, Nelson CC (August 2003). "Functional localization and competition between the androgen receptor and T-cell factor for nuclear beta-catenin: a means for inhibition of the Tcf signaling axis". Oncogene 22 (36): 5602–13. doi:10.1038/sj.onc.1206802. PMID 12944908.
- Pawlowski JE, Ertel JR, Allen MP, Xu M, Butler C, Wilson EM, Wierman ME (June 2002). "Liganded androgen receptor interaction with beta-catenin: nuclear co-localization and modulation of transcriptional activity in neuronal cells". J. Biol. Chem. 277 (23): 20702–10. doi:10.1074/jbc.M200545200. PMID 11916967.
- Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA (November 2000). "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor". Cancer Res. 60 (21): 5946–9. PMID 11085509.
- Yeh S, Hu YC, Rahman M, Lin HK, Hsu CL, Ting HJ, Kang HY, Chang C (October 2000). "Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells". Proc. Natl. Acad. Sci. U.S.A. 97 (21): 11256–61. doi:10.1073/pnas.190353897. PMC 17187. PMID 11016951.
- Sato N, Sadar MD, Bruchovsky N, Saatcioglu F, Rennie PS, Sato S, Lange PH, Gleave ME (July 1997). "Androgenic induction of prostate-specific antigen gene is repressed by protein-protein interaction between the androgen receptor and AP-1/c-Jun in the human prostate cancer cell line LNCaP". J. Biol. Chem. 272 (28): 17485–94. doi:10.1074/jbc.272.28.17485. PMID 9211894.
- Cifuentes E, Mataraza JM, Yoshida BA, Menon M, Sacks DB, Barrack ER, Reddy GP (January 2004). "Physical and functional interaction of androgen receptor with calmodulin in prostate cancer cells". Proc. Natl. Acad. Sci. U.S.A. 101 (2): 464–9. doi:10.1073/pnas.0307161101. PMC 327170. PMID 14695896.
- Lu ML, Schneider MC, Zheng Y, Zhang X, Richie JP (April 2001). "Caveolin-1 interacts with androgen receptor. A positive modulator of androgen receptor mediated transactivation". J. Biol. Chem. 276 (16): 13442–51. doi:10.1074/jbc.M006598200. PMID 11278309.
- Lee DK, Duan HO, Chang C (March 2001). "Androgen receptor interacts with the positive elongation factor P-TEFb and enhances the efficiency of transcriptional elongation". J. Biol. Chem. 276 (13): 9978–84. doi:10.1074/jbc.M002285200. PMID 11266437.
- Beauchemin AM, Gottlieb B, Beitel LK, Elhaji YA, Pinsky L, Trifiro MA (2001). "Cytochrome c oxidase subunit Vb interacts with human androgen receptor: a potential mechanism for neurotoxicity in spinobulbar muscular atrophy". Brain Res. Bull. 56 (3–4): 285–97. doi:10.1016/S0361-9230(01)00583-4. PMID 11719263.
- Kim J, Jia L, Stallcup MR, Coetzee GA (February 2005). "The role of protein kinase A pathway and cAMP responsive element-binding protein in androgen receptor-mediated transcription at the prostate-specific antigen locus". J. Mol. Endocrinol. 34 (1): 107–18. doi:10.1677/jme.1.01701. PMID 15691881.
- Frønsdal K, Engedal N, Slagsvold T, Saatcioglu F (November 1998). "CREB binding protein is a coactivator for the androgen receptor and mediates cross-talk with AP-1". J. Biol. Chem. 273 (48): 31853–9. doi:10.1074/jbc.273.48.31853. PMID 9822653.
- Ishitani K, Yoshida T, Kitagawa H, Ohta H, Nozawa S, Kato S (July 2003). "p54nrb acts as a transcriptional coactivator for activation function 1 of the human androgen receptor". Biochem. Biophys. Res. Commun. 306 (3): 660–5. doi:10.1016/S0006-291X(03)01021-0. PMID 12810069.
- Aarnisalo P, Palvimo JJ, Jänne OA (March 1998). "CREB-binding protein in androgen receptor-mediated signaling". Proc. Natl. Acad. Sci. U.S.A. 95 (5): 2122–7. doi:10.1073/pnas.95.5.2122. PMC 19270. PMID 9482849.
- Reutens AT, Watanabe G, Albanese C, McPhaul MJ, Balk SP, Pestell RG (1998). "Cyclin D1 binds activating mutants of the androgen receptor". US Endocrine Society Meeting (P1-528).
- Reutens AT, Fu M, Wang C, Albanese C, McPhaul MJ, Sun Z, Balk SP, Jänne OA, Palvimo JJ, Pestell RG (May 2001). "Cyclin D1 binds the androgen receptor and regulates hormone-dependent signaling in a p300/CBP-associated factor (P/CAF)-dependent manner". Mol. Endocrinol. 15 (5): 797–811. doi:10.1210/mend.15.5.0641. PMID 11328859.
- Petre-Draviam CE, Williams EB, Burd CJ, Gladden A, Moghadam H, Meller J, Diehl JA, Knudsen KE (January 2005). "A central domain of cyclin D1 mediates nuclear receptor corepressor activity". Oncogene 24 (3): 431–44. doi:10.1038/sj.onc.1208200. PMID 15558026.
- Knudsen KE, Cavenee WK, Arden KC (May 1999). "D-type cyclins complex with the androgen receptor and inhibit its transcriptional transactivation ability". Cancer Res. 59 (10): 2297–301. PMID 10344732.
- Lee DK, Duan HO, Chang C (March 2000). "From androgen receptor to the general transcription factor TFIIH. Identification of cdk activating kinase (CAK) as an androgen receptor NH(2)-terminal associated coactivator". J. Biol. Chem. 275 (13): 9308–13. doi:10.1074/jbc.275.13.9308. PMID 10734072.
- Wu K, Katiyar S, Witkiewicz A; et al. (April 2009). "The cell fate determination factor dachshund inhibits androgen receptor signaling and prostate cancer cellular growth". Cancer Res. 69 (8): 3347–55. doi:10.1158/0008-5472.CAN-08-3821. PMC 2669850. PMID 19351840.
- Lin DY, Fang HI, Ma AH, Huang YS, Pu YS, Jenster G, Kung HJ, Shih HM (December 2004). "Negative Modulation of Androgen Receptor Transcriptional Activity by Daxx". Mol. Cell. Biol. 24 (24): 10529–41. doi:10.1128/MCB.24.24.10529-10541.2004. PMC 533990. PMID 15572661.
- Wafa LA, Cheng H, Rao MA, Nelson CC, Cox M, Hirst M, Sadowski I, Rennie PS (October 2003). "Isolation and identification of L-dopa decarboxylase as a protein that binds to and enhances transcriptional activity of the androgen receptor using the repressed transactivator yeast two-hybrid system". Biochem. J. 375 (Pt 2): 373–83. doi:10.1042/BJ20030689. PMC 1223690. PMID 12864730.
- Niki T, Takahashi-Niki K, Taira T, Iguchi-Ariga SM, Ariga H (February 2003). "DJBP: a novel DJ-1-binding protein, negatively regulates the androgen receptor by recruiting histone deacetylase complex, and DJ-1 antagonizes this inhibition by abrogation of this complex". Mol. Cancer Res. 1 (4): 247–61. PMID 12612053.
- Bonaccorsi L, Carloni V, Muratori M, Formigli L, Zecchi S, Forti G, Baldi E (October 2004). "EGF receptor (EGFR) signaling promoting invasion is disrupted in androgen-sensitive prostate cancer cells by an interaction between EGFR and androgen receptor (AR)". Int. J. Cancer 112 (1): 78–86. doi:10.1002/ijc.20362. PMID 15305378.
- Bonaccorsi L, Muratori M, Carloni V, Marchiani S, Formigli L, Forti G, Baldi E (August 2004). "The androgen receptor associates with the epidermal growth factor receptor in androgen-sensitive prostate cancer cells". Steroids 69 (8–9): 549–52. doi:10.1016/j.steroids.2004.05.011. PMID 15288768.
- Li P, Lee H, Guo S, Unterman TG, Jenster G, Bai W (January 2003). "AKT-Independent Protection of Prostate Cancer Cells from Apoptosis Mediated through Complex Formation between the Androgen Receptor and FKHR". Mol. Cell. Biol. 23 (1): 104–18. doi:10.1128/MCB.23.1.104-118.2003. PMC 140652. PMID 12482965.
- Koshy B, Matilla T, Burright EN, Merry DE, Fischbeck KH, Orr HT, Zoghbi HY (September 1996). "Spinocerebellar ataxia type-1 and spinobulbar muscular atrophy gene products interact with glyceraldehyde-3-phosphate dehydrogenase". Hum. Mol. Genet. 5 (9): 1311–8. doi:10.1093/hmg/5.9.1311. PMID 8872471.
- Nishimura K, Ting HJ, Harada Y, Tokizane T, Nonomura N, Kang HY, Chang HC, Yeh S, Miyamoto H, Shin M, Aozasa K, Okuyama A, Chang C (August 2003). "Modulation of androgen receptor transactivation by gelsolin: a newly identified androgen receptor coregulator". Cancer Res. 63 (16): 4888–94. PMID 12941811.
- Rigas AC, Ozanne DM, Neal DE, Robson CN (November 2003). "The scaffolding protein RACK1 interacts with androgen receptor and promotes cross-talk through a protein kinase C signaling pathway". J. Biol. Chem. 278 (46): 46087–93. doi:10.1074/jbc.M306219200. PMID 12958311.
- Wang L, Lin HK, Hu YC, Xie S, Yang L, Chang C (July 2004). "Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells". J. Biol. Chem. 279 (31): 32444–52. doi:10.1074/jbc.M313963200. PMID 15178691.
- Gaughan L, Logan IR, Cook S, Neal DE, Robson CN (July 2002). "Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor". J. Biol. Chem. 277 (29): 25904–13. doi:10.1074/jbc.M203423200. PMID 11994312.
- Veldscholte J, Berrevoets CA, Brinkmann AO, Grootegoed JA, Mulder E (March 1992). "Anti-androgens and the mutated androgen receptor of LNCaP cells: differential effects on binding affinity, heat-shock protein interaction, and transcription activation". Biochemistry 31 (8): 2393–9. doi:10.1021/bi00123a026. PMID 1540595.
- Nemoto T, Ohara-Nemoto Y, Ota M (September 1992). "Association of the 90-kDa heat shock protein does not affect the ligand-binding ability of androgen receptor". J. Steroid Biochem. Mol. Biol. 42 (8): 803–12. doi:10.1016/0960-0760(92)90088-Z. PMID 1525041.
- Bai S, He B, Wilson EM (February 2005). "Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor Function by Modulating the Interdomain Interaction". Mol. Cell. Biol. 25 (4): 1238–57. doi:10.1128/MCB.25.4.1238-1257.2005. PMC 548016. PMID 15684378.
- Bai S, Wilson EM (March 2008). "Epidermal Growth Factor-Dependent Phosphorylation and Ubiquitinylation of MAGE-11 Regulates Its Interaction with the Androgen Receptor". Mol. Cell. Biol. 28 (6): 1947–63. doi:10.1128/MCB.01672-07. PMC 2268407. PMID 18212060.
- Wang Q, Sharma D, Ren Y, Fondell JD (November 2002). "A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression". J. Biol. Chem. 277 (45): 42852–8. doi:10.1074/jbc.M206061200. PMID 12218053.
- Sharma M, Zarnegar M, Li X, Lim B, Sun Z (November 2000). "Androgen receptor interacts with a novel MYST protein, HBO1". J. Biol. Chem. 275 (45): 35200–8. doi:10.1074/jbc.M004838200. PMID 10930412.
- Ueda T, Mawji NR, Bruchovsky N, Sadar MD (October 2002). "Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells". J. Biol. Chem. 277 (41): 38087–94. doi:10.1074/jbc.M203313200. PMID 12163482.
- Bevan CL, Hoare S, Claessens F, Heery DM, Parker MG (December 1999). "The AF1 and AF2 Domains of the Androgen Receptor Interact with Distinct Regions of SRC1". Mol. Cell. Biol. 19 (12): 8383–92. PMC 84931. PMID 10567563.
- Wang Q, Udayakumar TS, Vasaitis TS, Brodie AM, Fondell JD (April 2004). "Mechanistic relationship between androgen receptor polyglutamine tract truncation and androgen-dependent transcriptional hyperactivity in prostate cancer cells". J. Biol. Chem. 279 (17): 17319–28. doi:10.1074/jbc.M400970200. PMID 14966121.
- He B, Wilson EM (March 2003). "Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF Motifs". Mol. Cell. Biol. 23 (6): 2135–50. doi:10.1128/MCB.23.6.2135-2150.2003. PMC 149467. PMID 12612084.
- Tan JA, Hall SH, Petrusz P, French FS (September 2000). "Thyroid receptor activator molecule, TRAM-1, is an androgen receptor coactivator". Endocrinology 141 (9): 3440–50. doi:10.1210/endo.141.9.7680. PMID 10965917.
- Gnanapragasam VJ, Leung HY, Pulimood AS, Neal DE, Robson CN (December 2001). "Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer". Br. J. Cancer 85 (12): 1928–36. doi:10.1054/bjoc.2001.2179. PMC 2364015. PMID 11747336.
- He B, Minges JT, Lee LW, Wilson EM (March 2002). "The FXXLF motif mediates androgen receptor-specific interactions with coregulators". J. Biol. Chem. 277 (12): 10226–35. doi:10.1074/jbc.M111975200. PMID 11779876.
- Alen P, Claessens F, Schoenmakers E, Swinnen JV, Verhoeven G, Rombauts W, Peeters B (January 1999). "Interaction of the putative androgen receptor-specific coactivator ARA70/ELE1alpha with multiple steroid receptors and identification of an internally deleted ELE1beta isoform". Mol. Endocrinol. 13 (1): 117–28. doi:10.1210/mend.13.1.0214. PMID 9892017.
- Yeh S, Chang C (May 1996). "Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells". Proc. Natl. Acad. Sci. U.S.A. 93 (11): 5517–21. doi:10.1073/pnas.93.11.5517. PMC 39278. PMID 8643607.
- Miyamoto H, Yeh S, Wilding G, Chang C (June 1998). "Promotion of agonist activity of antiandrogens by the androgen receptor coactivator, ARA70, in human prostate cancer DU145 cells". Proc. Natl. Acad. Sci. U.S.A. 95 (13): 7379–84. doi:10.1073/pnas.95.13.7379. PMC 22623. PMID 9636157.
- Yeh S, Lin HK, Kang HY, Thin TH, Lin MF, Chang C (May 1999). "From HER2/Neu signal cascade to androgen receptor and its coactivators: A novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells". Proc. Natl. Acad. Sci. U.S.A. 96 (10): 5458–63. doi:10.1073/pnas.96.10.5458. PMC 21881. PMID 10318905.
- Zhou ZX, He B, Hall SH, Wilson EM, French FS (February 2002). "Domain interactions between coregulator ARA(70) and the androgen receptor (AR)". Mol. Endocrinol. 16 (2): 287–300. doi:10.1210/mend.16.2.0765. PMID 11818501.
- Gao T, Brantley K, Bolu E, McPhaul MJ (October 1999). "RFG (ARA70, ELE1) interacts with the human androgen receptor in a ligand-dependent fashion, but functions only weakly as a coactivator in cotransfection assays". Mol. Endocrinol. 13 (10): 1645–56. doi:10.1210/mend.13.10.0352. PMID 10517667.
- Goo YH, Na SY, Zhang H, Xu J, Hong S, Cheong J, Lee SK, Lee JW (February 2004). "Interactions between activating signal cointegrator-2 and the tumor suppressor retinoblastoma in androgen receptor transactivation". J. Biol. Chem. 279 (8): 7131–5. doi:10.1074/jbc.M312563200. PMID 14645241.
- Liao G, Chen LY, Zhang A, Godavarthy A, Xia F, Ghosh JC, Li H, Chen JD (February 2003). "Regulation of androgen receptor activity by the nuclear receptor corepressor SMRT". J. Biol. Chem. 278 (7): 5052–61. doi:10.1074/jbc.M206374200. PMID 12441355.
- Dotzlaw H, Moehren U, Mink S, Cato AC, Iñiguez Lluhí JA, Baniahmad A (April 2002). "The amino terminus of the human AR is target for corepressor action and antihormone agonism". Mol. Endocrinol. 16 (4): 661–73. doi:10.1210/me.16.4.661. PMID 11923464.
- Zhang Y, Fondell JD, Wang Q, Xia X, Cheng A, Lu ML, Hamburger AW (August 2002). "Repression of androgen receptor mediated transcription by the ErbB-3 binding protein, Ebp1". Oncogene 21 (36): 5609–18. doi:10.1038/sj.onc.1205638. PMID 12165860.
- Yang F, Li X, Sharma M, Zarnegar M, Lim B, Sun Z (May 2001). "Androgen receptor specifically interacts with a novel p21-activated kinase, PAK6". J. Biol. Chem. 276 (18): 15345–53. doi:10.1074/jbc.M010311200. PMID 11278661.
- Lee SR, Ramos SM, Ko A, Masiello D, Swanson KD, Lu ML, Balk SP (January 2002). "AR and ER interaction with a p21-activated kinase (PAK6)". Mol. Endocrinol. 16 (1): 85–99. doi:10.1210/me.16.1.85. PMID 11773441.
- Pero R, Lembo F, Palmieri EA, Vitiello C, Fedele M, Fusco A, Bruni CB, Chiariotti L (February 2002). "PATZ attenuates the RNF4-mediated enhancement of androgen receptor-dependent transcription". J. Biol. Chem. 277 (5): 3280–5. doi:10.1074/jbc.M109491200. PMID 11719514.
- Kotaja N, Aittomäki S, Silvennoinen O, Palvimo JJ, Jänne OA (December 2000). "ARIP3 (androgen receptor-interacting protein 3) and other PIAS (protein inhibitor of activated STAT) proteins differ in their ability to modulate steroid receptor-dependent transcriptional activation". Mol. Endocrinol. 14 (12): 1986–2000. doi:10.1210/mend.14.12.0569. PMID 11117529.
- Moilanen AM, Karvonen U, Poukka H, Yan W, Toppari J, Jänne OA, Palvimo JJ (February 1999). "A testis-specific androgen receptor coregulator that belongs to a novel family of nuclear proteins". J. Biol. Chem. 274 (6): 3700–4. doi:10.1074/jbc.274.6.3700. PMID 9920921.
- Zhao Y, Goto K, Saitoh M, Yanase T, Nomura M, Okabe T, Takayanagi R, Nawata H (August 2002). "Activation function-1 domain of androgen receptor contributes to the interaction between subnuclear splicing factor compartment and nuclear receptor compartment. Identification of the p102 U5 small nuclear ribonucleoprotein particle-binding protein as a coactivator for the receptor". J. Biol. Chem. 277 (33): 30031–9. doi:10.1074/jbc.M203811200. PMID 12039962.
- Lin HK, Hu YC, Lee DK, Chang C (October 2004). "Regulation of androgen receptor signaling by PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor suppressor through distinct mechanisms in prostate cancer cells". Mol. Endocrinol. 18 (10): 2409–23. doi:10.1210/me.2004-0117. PMID 15205473.
- Wang L, Hsu CL, Ni J, Wang PH, Yeh S, Keng P, Chang C (March 2004). "Human Checkpoint Protein hRad9 Functions as a Negative Coregulator To Repress Androgen Receptor Transactivation in Prostate Cancer Cells". Mol. Cell. Biol. 24 (5): 2202–13. doi:10.1128/MCB.24.5.2202-2213.2004. PMC 350564. PMID 14966297.
- Rao MA, Cheng H, Quayle AN, Nishitani H, Nelson CC, Rennie PS (December 2002). "RanBPM, a nuclear protein that interacts with and regulates transcriptional activity of androgen receptor and glucocorticoid receptor". J. Biol. Chem. 277 (50): 48020–7. doi:10.1074/jbc.M209741200. PMID 12361945.
- Beitel LK, Elhaji YA, Lumbroso R, Wing SS, Panet-Raymond V, Gottlieb B, Pinsky L, Trifiro MA (August 2002). "Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity". J. Mol. Endocrinol. 29 (1): 41–60. doi:10.1677/jme.0.0290041. PMID 12200228.
- Lu J, Danielsen M (November 1998). "Differential regulation of androgen and glucocorticoid receptors by retinoblastoma protein". J. Biol. Chem. 273 (47): 31528–33. doi:10.1074/jbc.273.47.31528. PMID 9813067.
- Yeh S, Miyamoto H, Nishimura K, Kang H, Ludlow J, Hsiao P, Wang C, Su C, Chang C (July 1998). "Retinoblastoma, a tumor suppressor, is a coactivator for the androgen receptor in human prostate cancer DU145 cells". Biochem. Biophys. Res. Commun. 248 (2): 361–7. doi:10.1006/bbrc.1998.8974. PMID 9675141.
- Miyamoto H, Rahman M, Takatera H, Kang HY, Yeh S, Chang HC, Nishimura K, Fujimoto N, Chang C (February 2002). "A dominant-negative mutant of androgen receptor coregulator ARA54 inhibits androgen receptor-mediated prostate cancer growth". J. Biol. Chem. 277 (7): 4609–17. doi:10.1074/jbc.M108312200. PMID 11673464.
- Kang HY, Yeh S, Fujimoto N, Chang C (March 1999). "Cloning and characterization of human prostate coactivator ARA54, a novel protein that associates with the androgen receptor". J. Biol. Chem. 274 (13): 8570–6. doi:10.1074/jbc.274.13.8570. PMID 10085091.
- Moilanen AM, Poukka H, Karvonen U, Häkli M, Jänne OA, Palvimo JJ (September 1998). "Identification of a Novel RING Finger Protein as a Coregulator in Steroid Receptor-Mediated Gene Transcription". Mol. Cell. Biol. 18 (9): 5128–39. PMC 109098. PMID 9710597.
- Poukka H, Aarnisalo P, Santti H, Jänne OA, Palvimo JJ (January 2000). "Coregulator small nuclear RING finger protein (SNURF) enhances Sp1- and steroid receptor-mediated transcription by different mechanisms". J. Biol. Chem. 275 (1): 571–9. doi:10.1074/jbc.275.1.571. PMID 10617653.
- Liu Y, Kim BO, Kao C, Jung C, Dalton JT, He JJ (May 2004). "Tip110, the human immunodeficiency virus type 1 (HIV-1) Tat-interacting protein of 110 kDa as a negative regulator of androgen receptor (AR) transcriptional activation". J. Biol. Chem. 279 (21): 21766–73. doi:10.1074/jbc.M314321200. PMID 15031286.
- Fu M, Liu M, Sauve AA; et al. (November 2006). "Hormonal control of androgen receptor function through SIRT1". Mol. Cell. Biol. 26 (21): 8122–35. doi:10.1128/MCB.00289-06. PMC 1636736. PMID 16923962.
- Chipuk JE, Cornelius SC, Pultz NJ, Jorgensen JS, Bonham MJ, Kim SJ, Danielpour D (January 2002). "The androgen receptor represses transforming growth factor-beta signaling through interaction with Smad3". J. Biol. Chem. 277 (2): 1240–8. doi:10.1074/jbc.M108855200. PMID 11707452.
- Hayes SA, Zarnegar M, Sharma M, Yang F, Peehl DM, ten Dijke P, Sun Z (March 2001). "SMAD3 represses androgen receptor-mediated transcription". Cancer Res. 61 (5): 2112–8. PMID 11280774.
- Kang HY, Huang KE, Chang SY, Ma WL, Lin WJ, Chang C (November 2002). "Differential modulation of androgen receptor-mediated transactivation by Smad3 and tumor suppressor Smad4". J. Biol. Chem. 277 (46): 43749–56. doi:10.1074/jbc.M205603200. PMID 12226080.
- Gobinet J, Auzou G, Nicolas JC, Sultan C, Jalaguier S (December 2001). "Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP". Biochemistry 40 (50): 15369–77. doi:10.1021/bi011384o. PMID 11735420.
- Unni E, Sun S, Nan B, McPhaul MJ, Cheskis B, Mancini MA, Marcelli M (October 2004). "Changes in androgen receptor nongenotropic signaling correlate with transition of LNCaP cells to androgen independence". Cancer Res. 64 (19): 7156–68. doi:10.1158/0008-5472.CAN-04-1121. PMID 15466214.
- Powell SM, Christiaens V, Voulgaraki D, Waxman J, Claessens F, Bevan CL (March 2004). "Mechanisms of androgen receptor signalling via steroid receptor coactivator-1 in prostate". Endocr. Relat. Cancer 11 (1): 117–30. doi:10.1677/erc.0.0110117. PMID 15027889.
- Yuan X, Lu ML, Li T, Balk SP (December 2001). "SRY interacts with and negatively regulates androgen receptor transcriptional activity". J. Biol. Chem. 276 (49): 46647–54. doi:10.1074/jbc.M108404200. PMID 11585838.
- Matsuda T, Junicho A, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A (April 2001). "Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells". Biochem. Biophys. Res. Commun. 283 (1): 179–87. doi:10.1006/bbrc.2001.4758. PMID 11322786.
- Ueda T, Bruchovsky N, Sadar MD (March 2002). "Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways". J. Biol. Chem. 277 (9): 7076–85. doi:10.1074/jbc.M108255200. PMID 11751884.
- Ting HJ, Yeh S, Nishimura K, Chang C (January 2002). "Supervillin associates with androgen receptor and modulates its transcriptional activity". Proc. Natl. Acad. Sci. U.S.A. 99 (2): 661–6. doi:10.1073/pnas.022469899. PMC 117362. PMID 11792840.
- Mu X, Chang C (October 2003). "TR2 orphan receptor functions as negative modulator for androgen receptor in prostate cancer cells PC-3". Prostate 57 (2): 129–33. doi:10.1002/pros.10282. PMID 12949936.
- Lee YF, Shyr CR, Thin TH, Lin WJ, Chang C (December 1999). "Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: A unique signaling pathway in the steroid receptor superfamily". Proc. Natl. Acad. Sci. U.S.A. 96 (26): 14724–9. doi:10.1073/pnas.96.26.14724. PMC 24715. PMID 10611280.
- Wang X, Yang Y, Guo X, Sampson ER, Hsu CL, Tsai MY, Yeh S, Wu G, Guo Y, Chang C (May 2002). "Suppression of androgen receptor transactivation by Pyk2 via interaction and phosphorylation of the ARA55 coregulator". J. Biol. Chem. 277 (18): 15426–31. doi:10.1074/jbc.M111218200. PMID 11856738.
- Hsiao PW, Chang C (August 1999). "Isolation and characterization of ARA160 as the first androgen receptor N-terminal-associated coactivator in human prostate cells". J. Biol. Chem. 274 (32): 22373–9. doi:10.1074/jbc.274.32.22373. PMID 10428808.
- Miyajima N, Maruyama S, Bohgaki M, Kano S, Shigemura M, Shinohara N, Nonomura K, Hatakeyama S (May 2008). "TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cells". Cancer Res. 68 (9): 3486–94. doi:10.1158/0008-5472.CAN-07-6059. PMID 18451177.
- Poukka H, Aarnisalo P, Karvonen U, Palvimo JJ, Jänne OA (July 1999). "Ubc9 interacts with the androgen receptor and activates receptor-dependent transcription". J. Biol. Chem. 274 (27): 19441–6. doi:10.1074/jbc.274.27.19441. PMID 10383460.
- Müller JM, Isele U, Metzger E, Rempel A, Moser M, Pscherer A, Breyer T, Holubarsch C, Buettner R, Schüle R (February 2000). "FHL2, a novel tissue-specific coactivator of the androgen receptor". EMBO J. 19 (3): 359–69. doi:10.1093/emboj/19.3.359. PMC 305573. PMID 10654935.
- Cheng S, Brzostek S, Lee SR, Hollenberg AN, Balk SP (July 2002). "Inhibition of the dihydrotestosterone-activated androgen receptor by nuclear receptor corepressor". Mol. Endocrinol. 16 (7): 1492–501. doi:10.1210/mend.16.7.0870. PMID 12089345.
- Hodgson MC, Astapova I, Cheng S, Lee LJ, Verhoeven MC, Choi E, Balk SP, Hollenberg AN (February 2005). "The androgen receptor recruits nuclear receptor CoRepressor (N-CoR) in the presence of mifepristone via its N and C termini revealing a novel molecular mechanism for androgen receptor antagonists". J. Biol. Chem. 280 (8): 6511–9. doi:10.1074/jbc.M408972200. PMID 15598662.
- Markus SM, Taneja SS, Logan SK, Li W, Ha S, Hittelman AB, Rogatsky I, Garabedian MJ (February 2002). "Identification and Characterization of ART-27, a Novel Coactivator for the Androgen Receptor N Terminus". Mol. Biol. Cell 13 (2): 670–82. doi:10.1091/mbc.01-10-0513. PMC 65658. PMID 11854421.
- Sharma M, Li X, Wang Y, Zarnegar M, Huang CY, Palvimo JJ, Lim B, Sun Z (November 2003). "hZimp10 is an androgen receptor co-activator and forms a complex with SUMO-1 at replication foci". EMBO J. 22 (22): 6101–14. doi:10.1093/emboj/cdg585. PMC 275443. PMID 14609956.
|Wikimedia Commons has media related to Androgen receptor.|
- GeneReviews/NCBI/NIH/UW entry on Androgen Insensitivity Syndrome
- OMIM entries on Androgen Insensitivity Syndrome
- GeneReviews/NIH/NCBI/UW entry on Spinal and Bulbar Muscular Atrophy, Kennedy's Disease, SBMA, X-Linked Spinal and Bulbar Muscular Atrophy
- OMIM entries on Spinal and Bulbar Muscular Atrophy, Kennedy's Disease, SBMA, X-Linked Spinal and Bulbar Muscular Atrophy
- Androgen Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)
- Brinkmann AO. "Androgen physiology: receptor and metabolic disorders" (PDF). In Robert McLachlan, editor. Endocrinology of Male Reproduction. Endotext.org. Retrieved 2008-04-29.
- Gottlieb B (2007-07-24). "The Androgen Receptor Gene Mutations Database Server". McGill University. Archived from the original on 22 April 2008. Retrieved 2008-04-29.
- Thompson J (2006-09-30). "Molecular Mechanisms of Androgen Receptor Interactions" (PDF). Helsinki University Biomedical Dissertations No. 80. University of Helsinki. Archived (PDF) from the original on 6 April 2008. Retrieved 2008-04-29.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Androgen receptor Provide feedback
No Pfam abstract.
Internal database links
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001103
Steroid or nuclear hormone receptors (NRs) constitute an important super-family of transcription regulators that are involved in diverse physiological functions, including control of embryonic development, cell differentiation and homeostasis. Members include the steroid hormone receptors and receptors for thyroid hormone, retinoids and 1,25-dihydroxy-vitamin D3. The proteins function as dimeric molecules in the nucleus to regulate the transcription of target genes in a ligand-responsive manner [PUBMED:7899080, PUBMED:8165128].
NRs are extremely important in medical research, a large number of them being implicated in diseases such as cancer, diabetes and hormone resistance syndromes. Many do not yet have a defined ligand and are accordingly termed "orphan" receptors. More than 300 NRs have been described to date and a new system has recently been introduced in an attempt to rationalise the increasingly complex set of names used to describe superfamily members.
The androgen receptor (AR) consists of 3 functional and structural domains: an N-terminal (modulatory) domain; a DNA binding domain (INTERPRO) that mediates specific binding to target DNA sequences (ligand-responsive elements); and a hormone binding domain. The N-terminal domain (NTD) is unique to the androgen receptors and spans approximately the first 530 residues; the highly-conserved DNA-binding domain is smaller (around 65 residues) and occupies the central portion of the protein; and the hormone ligand binding domain (LBD) lies at the receptor C terminus. In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity.
The LBDs of steroid hormone receptors fold into 12 helices that form a ligand-binding pocket. When an agonist is bound, helix 12 folds over the pocket to enclose the ligand [PUBMED:12089231]. When an antagonist is unbound, helix 12 is positioned away from the pocket in a way that interferes with the binding of coactivators to a groove in the hormone-binding domain formed after ligand binding. In AR, ligand binding that induces folding of helix 12 to overlie the pocket discloses a groove that binds a region of the NTD. Coactivator molecules can also bind to this groove, but the predominant site for coactivator binding to AR is in the NTD. AR ligand resides in a pocket and primarily contacts helices 4, 5, and 10. The DNA-binding region includes eight cysteine residues that form two coordination complexes, each composed of four cysteines and a Zn2+ ion. These two zinc fingers form the structure that binds to the major groove of DNA. The second zinc finger stabilises the binding complex by hydrophobic interactions with the first finger and contributes to specificity of receptor DNA binding. It is also necessary for receptor dimerisation that occurs during DNA binding
Defects in the androgen receptor cause testicular feminisation syndrome, androgen insensibility syndrome (AIS) [PUBMED:1307250, PUBMED:1569163]. AIS may be complete (CAIS), where external genitalia are phenotypically female; partial (PAIS), where genitalia are substantively ambiguous; or mild (MAIS), where external genitalia are normal male, or nearly so. Defects in the receptor also cause X-linked spinal and bulbar muscular atrophy (also known as Kennedy's disease).
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||nucleus (GO:0005634)|
|Molecular function||DNA binding (GO:0003677)|
|androgen receptor activity (GO:0004882)|
|steroid binding (GO:0005496)|
|Biological process||regulation of transcription, DNA-templated (GO:0006355)|
|androgen receptor signaling pathway (GO:0030521)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Author:||Mian N, Bateman A|
|Number in seed:||2|
|Number in full:||66|
|Average length of the domain:||320.60 aa|
|Average identity of full alignment:||62 %|
|Average coverage of the sequence by the domain:||48.19 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||13|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
There is 1 interaction for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Androgen_recep domain has been found. There are 5 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
Loading structure mapping...