2z4j

Structural highlights

Disease

[ANDR_HUMAN] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:300068]; previously known as testicular feminization syndrome (TFM). AIS is an X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21]} [:]^{[22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58]} [:]^{[59] [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] [70] [71]} Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:313200]; also known as Kennedy disease. SMAX1 is an X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. Note=Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.^[72] Note=Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor. Defects in AR are the cause of androgen insensitivity syndrome partial (PAIS) [MIM:312300]; also known as Reifenstein syndrome. PAIS is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations. [NR0B2_HUMAN] Defects in NR0B2 may be associated with obesity (OBESITY) [MIM:601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.^[73]

Function

[ANDR_HUMAN] Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.^{[74] [75] [76] [77] [78] [79] [80]} [NR0B2_HUMAN] Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1.^[81]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Androgen receptor

References

1. ↑ Lubahn DB, Brown TR, Simental JA, Higgs HN, Migeon CJ, Wilson EM, French FS. Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9534-8. PMID:2594783
2. ↑ Mowszowicz I, Lee HJ, Chen HT, Mestayer C, Portois MC, Cabrol S, Mauvais-Jarvis P, Chang C. A point mutation in the second zinc finger of the DNA-binding domain of the androgen receptor gene causes complete androgen insensitivity in two siblings with receptor-positive androgen resistance. Mol Endocrinol. 1993 Jul;7(7):861-9. PMID:8413310
3. ↑ Ris-Stalpers C, Trifiro MA, Kuiper GG, Jenster G, Romalo G, Sai T, van Rooij HC, Kaufman M, Rosenfield RL, Liao S, et al.. Substitution of aspartic acid-686 by histidine or asparagine in the human androgen receptor leads to a functionally inactive protein with altered hormone-binding characteristics. Mol Endocrinol. 1991 Oct;5(10):1562-9. PMID:1775137
4. ↑ Bohl CE, Miller DD, Chen J, Bell CE, Dalton JT. Structural basis for accommodation of nonsteroidal ligands in the androgen receptor. J Biol Chem. 2005 Nov 11;280(45):37747-54. Epub 2005 Aug 29. PMID:16129672 doi:http://dx.doi.org/10.1074/jbc.M507464200
5. ↑ Brown TR, Lubahn DB, Wilson EM, French FS, Migeon CJ, Corden JL. Functional characterization of naturally occurring mutant androgen receptors from subjects with complete androgen insensitivity. Mol Endocrinol. 1990 Dec;4(12):1759-72. PMID:2082179
6. ↑ Marcelli M, Zoppi S, Grino PB, Griffin JE, Wilson JD, McPhaul MJ. A mutation in the DNA-binding domain of the androgen receptor gene causes complete testicular feminization in a patient with receptor-positive androgen resistance. J Clin Invest. 1991 Mar;87(3):1123-6. PMID:1999491 doi:http://dx.doi.org/10.1172/JCI115076
7. ↑ Prior L, Bordet S, Trifiro MA, Mhatre A, Kaufman M, Pinsky L, Wrogeman K, Belsham DD, Pereira F, Greenberg C, et al.. Replacement of arginine 773 by cysteine or histidine in the human androgen receptor causes complete androgen insensitivity with different receptor phenotypes. Am J Hum Genet. 1992 Jul;51(1):143-55. PMID:1609793
8. ↑ Sweet CR, Behzadian MA, McDonough PG. A unique point mutation in the androgen receptor gene in a family with complete androgen insensitivity syndrome. Fertil Steril. 1992 Oct;58(4):703-7. PMID:1426313
9. ↑ Jakubiczka S, Werder EA, Wieacker P. Point mutation in the steroid-binding domain of the androgen receptor gene in a family with complete androgen insensitivity syndrome (CAIS). Hum Genet. 1992 Nov;90(3):311-2. PMID:1487249
10. ↑ Batch JA, Williams DM, Davies HR, Brown BD, Evans BA, Hughes IA, Patterson MN. Androgen receptor gene mutations identified by SSCP in fourteen subjects with androgen insensitivity syndrome. Hum Mol Genet. 1992 Oct;1(7):497-503. PMID:1307250
11. ↑ Nakao R, Haji M, Yanase T, Ogo A, Takayanagi R, Katsube T, Fukumaki Y, Nawata H. A single amino acid substitution (Met786----Val) in the steroid-binding domain of human androgen receptor leads to complete androgen insensitivity syndrome. J Clin Endocrinol Metab. 1992 May;74(5):1152-7. PMID:1569163
12. ↑ Wilson CM, Griffin JE, Wilson JD, Marcelli M, Zoppi S, McPhaul MJ. Immunoreactive androgen receptor expression in subjects with androgen resistance. J Clin Endocrinol Metab. 1992 Dec;75(6):1474-8. PMID:1464650
13. ↑ McPhaul MJ, Marcelli M, Zoppi S, Wilson CM, Griffin JE, Wilson JD. Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene. J Clin Invest. 1992 Nov;90(5):2097-101. PMID:1430233 doi:http://dx.doi.org/10.1172/JCI116093
14. ↑ Zoppi S, Marcelli M, Deslypere JP, Griffin JE, Wilson JD, McPhaul MJ. Amino acid substitutions in the DNA-binding domain of the human androgen receptor are a frequent cause of receptor-binding positive androgen resistance. Mol Endocrinol. 1992 Mar;6(3):409-15. PMID:1316540
15. ↑ De Bellis A, Quigley CA, Cariello NF, el-Awady MK, Sar M, Lane MV, Wilson EM, French FS. Single base mutations in the human androgen receptor gene causing complete androgen insensitivity: rapid detection by a modified denaturing gradient gel electrophoresis technique. Mol Endocrinol. 1992 Nov;6(11):1909-20. PMID:1480178
16. ↑ Lumbroso S, Lobaccaro JM, Belon C, Martin D, Chaussain JL, Sultan C. A new mutation within the deoxyribonucleic acid-binding domain of the androgen receptor gene in a family with complete androgen insensitivity syndrome. Fertil Steril. 1993 Nov;60(5):814-9. PMID:8224266
17. ↑ Lobaccaro JM, Lumbroso S, Ktari R, Dumas R, Sultan C. An exonic point mutation creates a MaeIII site in the androgen receptor gene of a family with complete androgen insensitivity syndrome. Hum Mol Genet. 1993 Jul;2(7):1041-3. PMID:8103398
18. ↑ Adeyemo O, Kallio PJ, Palvimo JJ, Kontula K, Janne OA. A single-base substitution in exon 6 of the androgen receptor gene causing complete androgen insensitivity: the mutated receptor fails to transactivate but binds to DNA in vitro. Hum Mol Genet. 1993 Nov;2(11):1809-12. PMID:8281140
19. ↑ Hiort O, Huang Q, Sinnecker GH, Sadeghi-Nejad A, Kruse K, Wolfe HJ, Yandell DW. Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: application for diagnosis, genetic counseling, and therapy. J Clin Endocrinol Metab. 1993 Jul;77(1):262-6. PMID:8325950
20. ↑ Lobaccaro JM, Lumbroso S, Berta P, Chaussain JL, Sultan C. Complete androgen insensitivity syndrome associated with a de novo mutation of the androgen receptor gene detected by single strand conformation polymorphism. J Steroid Biochem Mol Biol. 1993 Mar;44(3):211-6. PMID:8096390
21. ↑ Kazemi-Esfarjani P, Beitel LK, Trifiro M, Kaufman M, Rennie P, Sheppard P, Matusik R, Pinsky L. Substitution of valine-865 by methionine or leucine in the human androgen receptor causes complete or partial androgen insensitivity, respectively with distinct androgen receptor phenotypes. Mol Endocrinol. 1993 Jan;7(1):37-46. PMID:8446106
22. ↑ Beitel LK, Prior L, Vasiliou DM, Gottlieb B, Kaufman M, Lumbroso R, Alvarado C, McGillivray B, Trifiro M, Pinsky L. Complete androgen insensitivity due to mutations in the probable alpha-helical segments of the DNA-binding domain in the human androgen receptor. Hum Mol Genet. 1994 Jan;3(1):21-7. PMID:8162033
23. ↑ Hiort O, Wodtke A, Struve D, Zollner A, Sinnecker GH. Detection of point mutations in the androgen receptor gene using non-isotopic single strand conformation polymorphism analysis. German Collaborative Intersex Study Group. Hum Mol Genet. 1994 Jul;3(7):1163-6. PMID:7981687
24. ↑ Baldazzi L, Baroncini C, Pirazzoli P, Balsamo A, Capelli M, Marchetti G, Bernardi F, Cacciari E. Two mutations causing complete androgen insensitivity: a frame-shift in the steroid binding domain and a Cys-->Phe substitution in the second zinc finger of the androgen receptor. Hum Mol Genet. 1994 Jul;3(7):1169-70. PMID:7981689
25. ↑ Tsukada T, Inoue M, Tachibana S, Nakai Y, Takebe H. An androgen receptor mutation causing androgen resistance in undervirilized male syndrome. J Clin Endocrinol Metab. 1994 Oct;79(4):1202-7. PMID:7962294
26. ↑ Beitel LK, Kazemi-Esfarjani P, Kaufman M, Lumbroso R, DiGeorge AM, Killinger DW, Trifiro MA, Pinsky L. Substitution of arginine-839 by cysteine or histidine in the androgen receptor causes different receptor phenotypes in cultured cells and coordinate degrees of clinical androgen resistance. J Clin Invest. 1994 Aug;94(2):546-54. PMID:8040309 doi:http://dx.doi.org/10.1172/JCI117368
27. ↑ Marcelli M, Zoppi S, Wilson CM, Griffin JE, McPhaul MJ. Amino acid substitutions in the hormone-binding domain of the human androgen receptor alter the stability of the hormone receptor complex. J Clin Invest. 1994 Oct;94(4):1642-50. PMID:7929841 doi:http://dx.doi.org/10.1172/JCI117507
28. ↑ Yong EL, Ng SC, Roy AC, Yun G, Ratnam SS. Pregnancy after hormonal correction of severe spermatogenic defect due to mutation in androgen receptor gene. Lancet. 1994 Sep 17;344(8925):826-7. PMID:7993455
29. ↑ Ris-Stalpers C, Hoogenboezem T, Sleddens HF, Verleun-Mooijman MC, Degenhart HJ, Drop SL, Halley DJ, Oosterwijk JC, Hodgins MB, Trapman J, et al.. A practical approach to the detection of androgen receptor gene mutations and pedigree analysis in families with x-linked androgen insensitivity. Pediatr Res. 1994 Aug;36(2):227-34. PMID:7970939
30. ↑ Imai A, Ohno T, Iida K, Ohsuye K, Okano Y, Tamaya T. A frame-shift mutation of the androgen receptor gene in a patient with receptor-negative complete testicular feminization: comparison with a single base substitution in a receptor-reduced incomplete form. Ann Clin Biochem. 1995 Sep;32 ( Pt 5):482-6. PMID:8830623
31. ↑ Davies HR, Hughes IA, Patterson MN. Genetic counselling in complete androgen insensitivity syndrome: trinucleotide repeat polymorphisms, single-strand conformation polymorphism and direct detection of two novel mutations in the androgen receptor gene. Clin Endocrinol (Oxf). 1995 Jul;43(1):69-77. PMID:7641413
32. ↑ Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS. Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr Rev. 1995 Jun;16(3):271-321. PMID:7671849
33. ↑ Shkolny DL, Brown TR, Punnett HH, Kaufman M, Trifiro MA, Pinsky L. Characterization of alternative amino acid substitutions at arginine 830 of the androgen receptor that cause complete androgen insensitivity in three families. Hum Mol Genet. 1995 Apr;4(4):515-21. PMID:7633398
34. ↑ Belsham DD, Pereira F, Greenberg CR, Liao S, Wrogemann K. Leu-676-Pro mutation of the androgen receptor causes complete androgen insensitivity syndrome in a large Hutterite kindred. Hum Mutat. 1995;5(1):28-33. PMID:7537149 doi:http://dx.doi.org/10.1002/humu.1380050104
35. ↑ Murono K, Mendonca BB, Arnhold IJ, Rigon AC, Migeon CJ, Brown TR. Human androgen insensitivity due to point mutations encoding amino acid substitutions in the androgen receptor steroid-binding domain. Hum Mutat. 1995;6(2):152-62. PMID:7581399 doi:http://dx.doi.org/10.1002/humu.1380060208
36. ↑ Hiort O, Sinnecker GH, Holterhus PM, Nitsche EM, Kruse K. The clinical and molecular spectrum of androgen insensitivity syndromes. Am J Med Genet. 1996 May 3;63(1):218-22. PMID:8723113 doi:<218::AID-AJMG38>3.0.CO;2-P 10.1002/(SICI)1096-8628(19960503)63:1<218::AID-AJMG38>3.0.CO;2-P
37. ↑ Weidemann W, Linck B, Haupt H, Mentrup B, Romalo G, Stockklauser K, Brinkmann AO, Schweikert HU, Spindler KD. Clinical and biochemical investigations and molecular analysis of subjects with mutations in the androgen receptor gene. Clin Endocrinol (Oxf). 1996 Dec;45(6):733-9. PMID:9039340
38. ↑ Malmgren H, Gustavsson J, Tuvemo T, Dahl N. Rapid detection of a mutation hot-spot in the human androgen receptor. Clin Genet. 1996 Oct;50(4):202-5. PMID:9001799
39. ↑ Lumbroso S, Lobaccaro JM, Georget V, Leger J, Poujol N, Terouanne B, Evain-Brion D, Czernichow P, Sultan C. A novel substitution (Leu707Arg) in exon 4 of the androgen receptor gene causes complete androgen resistance. J Clin Endocrinol Metab. 1996 May;81(5):1984-8. PMID:8626869
40. ↑ Rodien P, Mebarki F, Mowszowicz I, Chaussain JL, Young J, Morel Y, Schaison G. Different phenotypes in a family with androgen insensitivity caused by the same M780I point mutation in the androgen receptor gene. J Clin Endocrinol Metab. 1996 Aug;81(8):2994-8. PMID:8768864
41. ↑ Bruggenwirth HT, Boehmer AL, Verleun-Mooijman MC, Hoogenboezem T, Kleijer WJ, Otten BJ, Trapman J, Brinkmann AO. Molecular basis of androgen insensitivity. J Steroid Biochem Mol Biol. 1996 Aug;58(5-6):569-75. PMID:8918984
42. ↑ Sutherland RW, Wiener JS, Hicks JP, Marcelli M, Gonzales ET Jr, Roth DR, Lamb DJ. Androgen receptor gene mutations are rarely associated with isolated penile hypospadias. J Urol. 1996 Aug;156(2 Pt 2):828-31. PMID:8683794
43. ↑ Lobaccaro JM, Poujol N, Chiche L, Lumbroso S, Brown TR, Sultan C. Molecular modeling and in vitro investigations of the human androgen receptor DNA-binding domain: application for the study of two mutations. Mol Cell Endocrinol. 1996 Feb 5;116(2):137-47. PMID:8647313
44. ↑ Imasaki K, Okabe T, Murakami H, Tanaka Y, Haji M, Takayanagi R, Nawata H. Androgen insensitivity syndrome due to new mutations in the DNA-binding domain of the androgen receptor. Mol Cell Endocrinol. 1996 Jun 18;120(1):15-24. PMID:8809734
45. ↑ Boehmer AL, Brinkmann AO, Niermeijer MF, Bakker L, Halley DJ, Drop SL. Germ-line and somatic mosaicism in the androgen insensitivity syndrome: implications for genetic counseling. Am J Hum Genet. 1997 Apr;60(4):1003-6. PMID:9106550
46. ↑ Essawi M, Gad YZ, el-Rouby O, Temtamy SA, Sabour YA, el-Awady MK. Molecular analysis of androgen resistance syndromes in Egyptian patients. Dis Markers. 1997 Apr;13(2):99-105. PMID:9160185
47. ↑ Sinnecker GH, Hiort O, Nitsche EM, Holterhus PM, Kruse K. Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group. Eur J Pediatr. 1997 Jan;156(1):7-14. PMID:9007482
48. ↑ Jakubiczka S, Nedel S, Werder EA, Schleiermacher E, Theile U, Wolff G, Wieacker P. Mutations of the androgen receptor gene in patients with complete androgen insensitivity. Hum Mutat. 1997;9(1):57-61. PMID:8990010 doi:<57::AID-HUMU10>3.0.CO;2-O 10.1002/(SICI)1098-1004(1997)9:1<57::AID-HUMU10>3.0.CO;2-O
49. ↑ Komori S, Sakata K, Tanaka H, Shima H, Koyama K. DNA analysis of the androgen receptor gene in two cases with complete androgen insensitivity syndrome. J Obstet Gynaecol Res. 1997 Jun;23(3):277-81. PMID:9255042
50. ↑ Ko TM, Yang YS, Wu MY, Kao CH, Hsu PM, Chuang SM, Lee TY. Complete androgen insensitivity syndrome. Molecular characterization in two Chinese women. J Reprod Med. 1997 Jul;42(7):424-8. PMID:9252933
51. ↑ Bevan CL, Hughes IA, Patterson MN. Wide variation in androgen receptor dysfunction in complete androgen insensitivity syndrome. J Steroid Biochem Mol Biol. 1997 Apr;61(1-2):19-26. PMID:9328206
52. ↑ Radmayr C, Culig Z, Glatzl J, Neuschmid-Kaspar F, Bartsch G, Klocker H. Androgen receptor point mutations as the underlying molecular defect in 2 patients with androgen insensitivity syndrome. J Urol. 1997 Oct;158(4):1553-6. PMID:9302173
53. ↑ Komori S, Kasumi H, Sakata K, Tanaka H, Hamada K, Koyama K. Molecular analysis of the androgen receptor gene in 4 patients with complete androgen insensitivity. Arch Gynecol Obstet. 1998;261(2):95-100. PMID:9544375
54. ↑ Cabral DF, Maciel-Guerra AT, Hackel C. Mutations of androgen receptor gene in Brazilian patients with male pseudohermaphroditism. Braz J Med Biol Res. 1998 Jun;31(6):775-8. PMID:9698822
55. ↑ Wang Q, Ghadessy FJ, Yong EL. Analysis of the transactivation domain of the androgen receptor in patients with male infertility. Clin Genet. 1998 Sep;54(3):185-92. PMID:9788719
56. ↑ Tanaka H, Komori S, Sakata K, Shima H, Koyama K. One additional mutation at exon A amplifies thermolability of androgen receptor in a case with complete androgen insensitivity syndrome. Gynecol Endocrinol. 1998 Apr;12(2):75-82. PMID:9610419
57. ↑ Lundberg Giwercman Y, Nikoshkov A, Lindsten K, Bystrom B, Pousette A, Chibalin AV, Arvidsson S, Tiulpakov A, Semitcheva TV, Peterkova V, Hagenfeldt K, Ritzen EM, Wedell A. Functional characterisation of mutations in the ligand-binding domain of the androgen receptor gene in patients with androgen insensitivity syndrome. Hum Genet. 1998 Oct;103(4):529-31. PMID:9856504
58. ↑ Dork T, Schnieders F, Jakubiczka S, Wieacker P, Schroeder-Kurth T, Schmidtke J. A new missense substitution at a mutational hot spot of the androgen receptor in siblings with complete androgen insensitivity syndrome. Hum Mutat. 1998;11(4):337-9. PMID:9554754
59. ↑ Wang Q, Ghadessy FJ, Trounson A, de Kretser D, McLachlan R, Ng SC, Yong EL. Azoospermia associated with a mutation in the ligand-binding domain of an androgen receptor displaying normal ligand binding, but defective trans-activation. J Clin Endocrinol Metab. 1998 Dec;83(12):4303-9. PMID:9851768
60. ↑ Hiort O, Sinnecker GH, Holterhus PM, Nitsche EM, Kruse K. Inherited and de novo androgen receptor gene mutations: investigation of single-case families. J Pediatr. 1998 Jun;132(6):939-43. PMID:9627582
61. ↑ Gottlieb B, Vasiliou DM, Lumbroso R, Beitel LK, Pinsky L, Trifiro MA. Analysis of exon 1 mutations in the androgen receptor gene. Hum Mutat. 1999;14(6):527-39. PMID:10571951 doi:<527::AID-HUMU12>3.0.CO;2-X 10.1002/(SICI)1098-1004(199912)14:6<527::AID-HUMU12>3.0.CO;2-X
62. ↑ Chen CP, Chern SR, Wang TY, Wang W, Wang KL, Jeng CJ. Androgen receptor gene mutations in 46,XY females with germ cell tumours. Hum Reprod. 1999 Mar;14(3):664-70. PMID:10221692
63. ↑ Kanayama H, Naroda T, Inoue Y, Kurokawa Y, Kagawa S. A case of complete testicular feminization: laparoscopic orchiectomy and analysis of androgen receptor gene mutation. Int J Urol. 1999 Jun;6(6):327-30. PMID:10404311
64. ↑ Shkolny DL, Beitel LK, Ginsberg J, Pekeles G, Arbour L, Pinsky L, Trifiro MA. Discordant measures of androgen-binding kinetics in two mutant androgen receptors causing mild or partial androgen insensitivity, respectively. J Clin Endocrinol Metab. 1999 Feb;84(2):805-10. PMID:10022458
65. ↑ Peters I, Weidemann W, Romalo G, Knorr D, Schweikert HU, Spindler KD. An androgen receptor mutation in the direct vicinity of the proposed C-terminal alpha-helix of the ligand binding domain containing the AF-2 transcriptional activating function core is associated with complete androgen insensitivity. Mol Cell Endocrinol. 1999 Feb 25;148(1-2):47-53. PMID:10221770
66. ↑ Holterhus PM, Wiebel J, Sinnecker GH, Bruggenwirth HT, Sippell WG, Brinkmann AO, Kruse K, Hiort O. Clinical and molecular spectrum of somatic mosaicism in androgen insensitivity syndrome. Pediatr Res. 1999 Dec;46(6):684-90. PMID:10590024
67. ↑ Yaegashi N, Uehara S, Senoo M, Sato J, Fujiwara J, Funato T, Sasaki T, Yajima A. Point mutations in the steroid-binding domain of the androgen receptor gene of five Japanese patients with androgen insensitivity syndrome. Tohoku J Exp Med. 1999 Mar;187(3):263-72. PMID:10458483
68. ↑ Ahmed SF, Cheng A, Dovey L, Hawkins JR, Martin H, Rowland J, Shimura N, Tait AD, Hughes IA. Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab. 2000 Feb;85(2):658-65. PMID:10690872
69. ↑ Chavez B, Mendez JP, Ulloa-Aguirre A, Larrea F, Vilchis F. Eight novel mutations of the androgen receptor gene in patients with androgen insensitivity syndrome. J Hum Genet. 2001;46(10):560-5. PMID:11587068 doi:10.1007/s100380170021
70. ↑ Sills ES, Sholes TE, Perloe M, Kaplan CR, Davis JG, Tucker MJ. Characterization of a novel receptor mutation A-->T at exon 4 in complete androgen insensitivity syndrome and a carrier sibling via bidirectional polymorphism sequence analysis. Int J Mol Med. 2002 Jan;9(1):45-8. PMID:11744994
71. ↑ Jaaskelainen J, Deeb A, Schwabe JW, Mongan NP, Martin H, Hughes IA. Human androgen receptor gene ligand-binding-domain mutations leading to disrupted interaction between the N- and C-terminal domains. J Mol Endocrinol. 2006 Apr;36(2):361-8. PMID:16595706 doi:36/2/361
72. ↑ Echaniz-Laguna A, Rousso E, Anheim M, Cossee M, Tranchant C. A family with early-onset and rapidly progressive X-linked spinal and bulbar muscular atrophy. Neurology. 2005 Apr 26;64(8):1458-60. PMID:15851746 doi:64/8/1458
73. ↑ Nishigori H, Tomura H, Tonooka N, Kanamori M, Yamada S, Sho K, Inoue I, Kikuchi N, Onigata K, Kojima I, Kohama T, Yamagata K, Yang Q, Matsuzawa Y, Miki T, Seino S, Kim MY, Choi HS, Lee YK, Moore DD, Takeda J. Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):575-80. Epub 2001 Jan 2. PMID:11136233 doi:10.1073/pnas.021544398
74. ↑ Hofman K, Swinnen JV, Claessens F, Verhoeven G, Heyns W. The retinoblastoma protein-associated transcription repressor RBaK interacts with the androgen receptor and enhances its transcriptional activity. J Mol Endocrinol. 2003 Dec;31(3):583-96. PMID:14664718
75. ↑ Leister P, Felten A, Chasan AI, Scheidtmann KH. ZIP kinase plays a crucial role in androgen receptor-mediated transcription. Oncogene. 2008 May 22;27(23):3292-300. Epub 2007 Dec 17. PMID:18084323 doi:10.1038/sj.onc.1210995
76. ↑ Xu K, Shimelis H, Linn DE, Jiang R, Yang X, Sun F, Guo Z, Chen H, Li W, Chen H, Kong X, Melamed J, Fang S, Xiao Z, Veenstra TD, Qiu Y. Regulation of androgen receptor transcriptional activity and specificity by RNF6-induced ubiquitination. Cancer Cell. 2009 Apr 7;15(4):270-82. doi: 10.1016/j.ccr.2009.02.021. PMID:19345326 doi:10.1016/j.ccr.2009.02.021
77. ↑ Gordon V, Bhadel S, Wunderlich W, Zhang J, Ficarro SB, Mollah SA, Shabanowitz J, Hunt DF, Xenarios I, Hahn WC, Conaway M, Carey MF, Gioeli D. CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation. Mol Endocrinol. 2010 Dec;24(12):2267-80. doi: 10.1210/me.2010-0238. Epub 2010 Oct, 27. PMID:20980437 doi:10.1210/me.2010-0238
78. ↑ Estebanez-Perpina E, Moore JM, Mar E, Delgado-Rodrigues E, Nguyen P, Baxter JD, Buehrer BM, Webb P, Fletterick RJ, Guy RK. The molecular mechanisms of coactivator utilization in ligand-dependent transactivation by the androgen receptor. J Biol Chem. 2005 Mar 4;280(9):8060-8. Epub 2004 Nov 24. PMID:15563469 doi:10.1074/jbc.M407046200
79. ↑ Askew EB, Gampe RT Jr, Stanley TB, Faggart JL, Wilson EM. Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone. J Biol Chem. 2007 Aug 31;282(35):25801-16. Epub 2007 Jun 25. PMID:17591767 doi:10.1074/jbc.M703268200
80. ↑ Estebanez-Perpina E, Arnold LA, Nguyen P, Rodrigues ED, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P, Fletterick RJ. A surface on the androgen receptor that allosterically regulates coactivator binding. Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16074-9. Epub 2007 Oct 2. PMID:17911242
81. ↑ Kim JY, Chu K, Kim HJ, Seong HA, Park KC, Sanyal S, Takeda J, Ha H, Shong M, Tsai MJ, Choi HS. Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD. Mol Endocrinol. 2004 Apr;18(4):776-90. Epub 2004 Jan 29. PMID:14752053 doi:10.1210/me.2003-0311
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