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'''Unreleased structure'''


The entry 4ql8 is ON HOLD  until Paper Publication
==Crystal structure of Androgen Receptor in complex with the ligand==
<StructureSection load='4ql8' size='340' side='right'caption='[[4ql8]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ql8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QL8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QL8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JAD:2-CHLORO-4-[(3S,3AS,4S)-4-HYDROXY-3-METHOXY-3A,4,5,6-TETRAHYDRO-3H-PYRROLO[1,2-B]PYRAZOL-2-YL]-3-METHYLBENZONITRILE'>JAD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ql8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ql8 OCA], [https://pdbe.org/4ql8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ql8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ql8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ql8 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[https://omim.org/entry/300068 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.<ref>PMID:2594783</ref> <ref>PMID:8413310</ref> <ref>PMID:1775137</ref> <ref>PMID:16129672</ref> <ref>PMID:2082179</ref> <ref>PMID:1999491</ref> <ref>PMID:1609793</ref> <ref>PMID:1426313</ref> <ref>PMID:1487249</ref> <ref>PMID:1307250</ref> <ref>PMID:1569163</ref> <ref>PMID:1464650</ref> <ref>PMID:1430233</ref> <ref>PMID:1316540</ref> <ref>PMID:1480178</ref> <ref>PMID:8224266</ref> <ref>PMID:8103398</ref> <ref>PMID:8281140</ref> <ref>PMID:8325950</ref> <ref>PMID:8096390</ref> <ref>PMID:8446106</ref> [:]<ref>PMID:8162033</ref> <ref>PMID:7981687</ref> <ref>PMID:7981689</ref> <ref>PMID:7962294</ref> <ref>PMID:8040309</ref> <ref>PMID:7929841</ref> <ref>PMID:7993455</ref> <ref>PMID:7970939</ref> <ref>PMID:8830623</ref> <ref>PMID:7641413</ref> <ref>PMID:7671849</ref> <ref>PMID:7633398</ref> <ref>PMID:7537149</ref> <ref>PMID:7581399</ref> <ref>PMID:8723113</ref> <ref>PMID:9039340</ref> <ref>PMID:9001799</ref> <ref>PMID:8626869</ref> <ref>PMID:8768864</ref> <ref>PMID:8918984</ref> <ref>PMID:8683794</ref> <ref>PMID:8647313</ref> <ref>PMID:8809734</ref> <ref>PMID:9106550</ref> <ref>PMID:9160185</ref> <ref>PMID:9007482</ref> <ref>PMID:8990010</ref> <ref>PMID:9255042</ref> <ref>PMID:9252933</ref> <ref>PMID:9328206</ref> <ref>PMID:9302173</ref> <ref>PMID:9544375</ref> <ref>PMID:9698822</ref> <ref>PMID:9788719</ref> <ref>PMID:9610419</ref> <ref>PMID:9856504</ref> <ref>PMID:9554754</ref> [:]<ref>PMID:9851768</ref> <ref>PMID:9627582</ref> <ref>PMID:10571951</ref> <ref>PMID:10221692</ref> <ref>PMID:10404311</ref> <ref>PMID:10022458</ref> <ref>PMID:10221770</ref> <ref>PMID:10590024</ref> <ref>PMID:10458483</ref> <ref>PMID:10690872</ref> <ref>PMID:11587068</ref> <ref>PMID:11744994</ref> <ref>PMID:16595706</ref>  Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:[https://omim.org/entry/313200 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.<ref>PMID:15851746</ref>  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:[https://omim.org/entry/312300 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.
== Function ==
[https://www.uniprot.org/uniprot/ANDR_HUMAN 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.<ref>PMID:14664718</ref> <ref>PMID:18084323</ref> <ref>PMID:19345326</ref> <ref>PMID:20980437</ref> <ref>PMID:15563469</ref> <ref>PMID:17591767</ref> <ref>PMID:17911242</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We describe the synthesis and characterization of 3-alkoxy-pyrrolo[1,2-b]pyrazolines as novel selective androgen receptor (AR) modulators that possess excellent physicochemical properties for transdermal administration. Compound 26 bound to human AR with an IC50 of 0.7 nM with great selectivity over other nuclear hormone receptors and potently activated AR in a C2C12 muscle cell reporter gene assay with an EC50 of 0.5 nM. It showed high aqueous solubility of 1.3 g/L at pH 7.4, and an in silico model as well as a customized parallel artificial membrane permeability assay indicated good skin permeation. Indeed, when measuring skin permeation through excised human skin, an excellent flux of 2 mug/(cm(2).h) was determined without any permeation enhancers. In a 2 week Hershberger model using castrated rats, the compound showed dose-dependent effects fully restoring skeletal muscle weight at 0.3 mg/kg/day after subcutaneous administration with high selectivity over prostate stimulation.


Authors: Rao, K.N., Sangeetha, R., Chakshusmathi, G., Sanjitha, S., Subramanya, H.S.
3-alkoxy-pyrrolo[1,2-b]pyrazolines as selective androgen receptor modulators with ideal physicochemical properties for transdermal administration.,Ullrich T, Sasmal S, Boorgu V, Pasagadi S, Cheera S, Rajagopalan S, Bhumireddy A, Shashikumar D, Chelur S, Belliappa C, Pandit C, Krishnamurthy N, Mukherjee S, Ramanathan A, Ghadiyaram C, Ramachandra M, Santos PG, Lagu B, Bock MG, Perrone MH, Weiler S, Keller H J Med Chem. 2014 Sep 11;57(17):7396-411. doi: 10.1021/jm5009049. Epub 2014 Aug, 26. PMID:25121964<ref>PMID:25121964</ref>


Description: Crystal structure of Androgen Receptor in complex with the ligand
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Subramanya, H.S]]
<div class="pdbe-citations 4ql8" style="background-color:#fffaf0;"></div>
[[Category: Chakshusmathi, G]]
 
[[Category: Sanjitha, S]]
==See Also==
[[Category: Sangeetha, R]]
*[[Androgen receptor 3D structures|Androgen receptor 3D structures]]
[[Category: Rao, K.N]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ghadiyaram C]]
[[Category: Krishnamurthy N]]
[[Category: Sangeetha R]]
[[Category: Sasmal S]]
[[Category: Subramanya HS]]

Latest revision as of 18:07, 8 November 2023

Crystal structure of Androgen Receptor in complex with the ligandCrystal structure of Androgen Receptor in complex with the ligand

Structural highlights

4ql8 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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.[73] [74] [75] [76] [77] [78] [79]

Publication Abstract from PubMed

We describe the synthesis and characterization of 3-alkoxy-pyrrolo[1,2-b]pyrazolines as novel selective androgen receptor (AR) modulators that possess excellent physicochemical properties for transdermal administration. Compound 26 bound to human AR with an IC50 of 0.7 nM with great selectivity over other nuclear hormone receptors and potently activated AR in a C2C12 muscle cell reporter gene assay with an EC50 of 0.5 nM. It showed high aqueous solubility of 1.3 g/L at pH 7.4, and an in silico model as well as a customized parallel artificial membrane permeability assay indicated good skin permeation. Indeed, when measuring skin permeation through excised human skin, an excellent flux of 2 mug/(cm(2).h) was determined without any permeation enhancers. In a 2 week Hershberger model using castrated rats, the compound showed dose-dependent effects fully restoring skeletal muscle weight at 0.3 mg/kg/day after subcutaneous administration with high selectivity over prostate stimulation.

3-alkoxy-pyrrolo[1,2-b]pyrazolines as selective androgen receptor modulators with ideal physicochemical properties for transdermal administration.,Ullrich T, Sasmal S, Boorgu V, Pasagadi S, Cheera S, Rajagopalan S, Bhumireddy A, Shashikumar D, Chelur S, Belliappa C, Pandit C, Krishnamurthy N, Mukherjee S, Ramanathan A, Ghadiyaram C, Ramachandra M, Santos PG, Lagu B, Bock MG, Perrone MH, Weiler S, Keller H J Med Chem. 2014 Sep 11;57(17):7396-411. doi: 10.1021/jm5009049. Epub 2014 Aug, 26. PMID:25121964[80]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

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
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  73. ↑ 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
  74. ↑ 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
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