2ax7 - Revision history

OCA at 07:31, 23 August 2023

2023-08-23T07:31:06Z

←Older revision		Revision as of 07:31, 23 August 2023
Line 3:		Line 3:
	<StructureSection load='2ax7' size='340' side='right'caption='[[2ax7]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='2ax7' size='340' side='right'caption='[[2ax7]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2ax7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AX7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2ax7]] 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=2AX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AX7 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=FHM:S-3-(4-FLUOROPHENOXY)-2-HYDROXY-2-METHYL-N~~-[~~4-NITRO-3-(TRIFLUOROMETHYL)PHENYL~~]~~PROPANAMIDE'>FHM</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.9Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;'>~~[~~[2ax6\|2ax6~~]~~], [[2ax8\|2ax8]], [[2ax9\|2ax9]], [[2axa\|2axa]]</div></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FHM:S-3-(4-FLUOROPHENOXY)-2-HYDROXY-2-METHYL-N-[4-NITRO-3-(TRIFLUOROMETHYL)PHENYL]PROPANAMIDE'>FHM</scene></td></tr>
-	~~<tr id='gene~~'>~~<td class="sblockLbl"><b>[[Gene\|Gene:]]~~</b>~~</td><td class="sblockDat">Ar ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</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=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [https://pdbe.org/2ax7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [https://www.ebi.ac.uk/pdbsum/2ax7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ax7 ProSAT]</span></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=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [https://pdbe.org/2ax7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [https://www.ebi.ac.uk/pdbsum/2ax7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ax7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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.	+	[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 ==		== 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>	+	[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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 39:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bell~~, C E~~]]	+	[[Category: Bell CE]]
-	[[Category: Bohl~~, C E~~]]	+	[[Category: Bohl CE]]
-	[[Category: Chen, J]]	+	[[Category: Chen J]]
-	[[Category: Dalton~~, J T~~]]	+	[[Category: Dalton JT]]
-	[[Category: Miller~~, D D]]~~	+	[[Category: Miller DD]]
-	~~[[Category: Transcription~~]]	+

OCA at 08:39, 27 January 2021

2021-01-27T08:39:38Z

←Older revision		Revision as of 08:39, 27 January 2021
Line 1:		Line 1:

	==Crystal Structure Of The Androgen Receptor Ligand Binding Domain T877A Mutant In Complex With S-1==		==Crystal Structure Of The Androgen Receptor Ligand Binding Domain T877A Mutant In Complex With S-1==
-	<StructureSection load='2ax7' size='340' side='right' caption='[[2ax7]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='2ax7' size='340' side='right'caption='[[2ax7]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2ax7]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2AX7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2ax7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AX7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FHM:S-3-(4-FLUOROPHENOXY)-2-HYDROXY-2-METHYL-N-[4-NITRO-3-(TRIFLUOROMETHYL)PHENYL]PROPANAMIDE'>FHM</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FHM:S-3-(4-FLUOROPHENOXY)-2-HYDROXY-2-METHYL-N-[4-NITRO-3-(TRIFLUOROMETHYL)PHENYL]PROPANAMIDE'>FHM</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ax6\|2ax6]], [[2ax8\|2ax8]], [[2ax9\|2ax9]], [[2axa\|2axa]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ax6\|2ax6]], [[2ax8\|2ax8]], [[2ax9\|2ax9]], [[2axa\|2axa]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ar ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ar ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [~~http~~://pdbe.org/2ax7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2ax7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2ax7 ProSAT]</span></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=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [https://pdbe.org/2ax7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [https://www.ebi.ac.uk/pdbsum/2ax7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ax7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[~~http~~://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:[~~http~~://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:[~~http~~://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.	+	[[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 ==		== Function ==
-	[[~~http~~://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>	+	[[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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ax/2ax7_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ax/2ax7_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 32:		Line 32:
	</div>		</div>
	<div class="pdbe-citations 2ax7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2ax7" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Androgen receptor 3D structures\|Androgen receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 37:		Line 40:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bell, C E]]		[[Category: Bell, C E]]
	[[Category: Bohl, C E]]		[[Category: Bohl, C E]]

OCA at 12:31, 12 October 2017

2017-10-12T12:31:37Z

←Older revision		Revision as of 12:31, 12 October 2017
Line 1:		Line 1:
		+
	==Crystal Structure Of The Androgen Receptor Ligand Binding Domain T877A Mutant In Complex With S-1==		==Crystal Structure Of The Androgen Receptor Ligand Binding Domain T877A Mutant In Complex With S-1==
	<StructureSection load='2ax7' size='340' side='right' caption='[[2ax7]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='2ax7' size='340' side='right' caption='[[2ax7]], [[Resolution\|resolution]] 1.90Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ax6\|2ax6]], [[2ax8\|2ax8]], [[2ax9\|2ax9]], [[2axa\|2axa]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ax6\|2ax6]], [[2ax8\|2ax8]], [[2ax9\|2ax9]], [[2axa\|2axa]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ar ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ar ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [http://pdbe.org/2ax7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [http://www.ebi.ac.uk/pdbsum/2ax7 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [http://pdbe.org/2ax7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [http://www.ebi.ac.uk/pdbsum/2ax7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ax7 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 31:		Line 32:
	</div>		</div>
	<div class="pdbe-citations 2ax7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2ax7" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Androgen receptor\|Androgen receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:34, 8 February 2016

2016-02-08T19:34:33Z

←Older revision		Revision as of 19:34, 8 February 2016
Line 20:		Line 20:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ax7 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 14:43, 10 September 2015

2015-09-10T14:43:54Z

←Older revision		Revision as of 14:43, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='2ax7' size='340' side='right' caption='[[2ax7]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='2ax7' size='340' side='right' caption='[[2ax7]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2ax7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AX7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2ax7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AX7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FHM:S-3-(4-FLUOROPHENOXY)-2-HYDROXY-2-METHYL-N-[4-NITRO-3-(TRIFLUOROMETHYL)PHENYL]PROPANAMIDE'>FHM</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FHM:S-3-(4-FLUOROPHENOXY)-2-HYDROXY-2-METHYL-N-[4-NITRO-3-(TRIFLUOROMETHYL)PHENYL]PROPANAMIDE'>FHM</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ax6\|2ax6]], [[2ax8\|2ax8]], [[2ax9\|2ax9]], [[2axa\|2axa]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ax6\|2ax6]], [[2ax8\|2ax8]], [[2ax9\|2ax9]], [[2axa\|2axa]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ar ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ar ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [http://www.ebi.ac.uk/pdbsum/2ax7 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [http://pdbe.org/2ax7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [http://www.ebi.ac.uk/pdbsum/2ax7 PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 30:		Line 30:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 2ax7" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 37:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Bell, C E]]		[[Category: Bell, C E]]
	[[Category: Bohl, C E]]		[[Category: Bohl, C E]]

OCA at 08:57, 8 January 2015

2015-01-08T08:57:27Z

←Older revision		Revision as of 08:57, 8 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2ax7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AX7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[2ax7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AX7 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FHM:S-3-(4-FLUOROPHENOXY)-2-HYDROXY-2-METHYL-N-[4-NITRO-3-(TRIFLUOROMETHYL)PHENYL]PROPANAMIDE'>FHM</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FHM:S-3-(4-FLUOROPHENOXY)-2-HYDROXY-2-METHYL-N-[4-NITRO-3-(TRIFLUOROMETHYL)PHENYL]PROPANAMIDE'>FHM</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ax6\|2ax6]], [[2ax8\|2ax8]], [[2ax9\|2ax9]], [[2axa\|2axa]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ax6\|2ax6]], [[2ax8\|2ax8]], [[2ax9\|2ax9]], [[2axa\|2axa]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ar ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ar ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [http://www.ebi.ac.uk/pdbsum/2ax7 PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [http://www.ebi.ac.uk/pdbsum/2ax7 PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[http://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:[http://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:[http://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.		[[http://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[http://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:[http://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:[http://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.
Line 38:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Bell, C E.]]	+	[[Category: Bell, C E]]
-	[[Category: Bohl, C E.]]	+	[[Category: Bohl, C E]]
-	[[Category: Chen, J.]]	+	[[Category: Chen, J]]
-	[[Category: Dalton, J T.]]	+	[[Category: Dalton, J T]]
-	[[Category: Miller, D D.]]	+	[[Category: Miller, D D]]
	[[Category: Transcription]]		[[Category: Transcription]]

OCA at 01:35, 30 September 2014

2014-09-30T01:35:44Z

←Older revision		Revision as of 01:35, 30 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2ax7\| PDB=2ax7 \| SCENE= }}~~	+	==Crystal Structure Of The Androgen Receptor Ligand Binding Domain T877A Mutant In Complex With S-1==
-	===Crystal Structure Of The Androgen Receptor Ligand Binding Domain T877A Mutant In Complex With S-1===	+	<StructureSection load='2ax7' size='340' side='right' caption='[[2ax7]], [[Resolution\|resolution]] 1.90Å' scene=''>
-	~~{{ABSTRACT_PUBMED_16129672}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[2ax7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AX7 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FHM:S-3-(4-FLUOROPHENOXY)-2-HYDROXY-2-METHYL-N-[4-NITRO-3-(TRIFLUOROMETHYL)PHENYL]PROPANAMIDE'>FHM</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[2ax6\|2ax6]], [[2ax8\|2ax8]], [[2ax9\|2ax9]], [[2axa\|2axa]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Ar ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ax7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ax7 RCSB], [http://www.ebi.ac.uk/pdbsum/2ax7 PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[http://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:[http://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:[http://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 ==
		+	[[http://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>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ax/2ax7_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The mechanism by which the androgen receptor (AR) distinguishes between agonist and antagonist ligands is poorly understood. AR antagonists are currently used to treat prostate cancer. However, mutations commonly develop in patients that convert these compounds to agonists. Recently, our laboratory discovered selective androgen receptor modulators, which structurally resemble the nonsteroidal AR antagonists bicalutamide and hydroxyflutamide but act as agonists for the androgen receptor in a tissue-selective manner. To investigate why subtle structural changes to both the ligand and the receptor (i.e. mutations) result in drastic changes in activity, we studied structure-activity relationships for nonsteroidal AR ligands through crystallography and site-directed mutagenesis, comparing bound conformations of R-bicalutamide, hydroxyflutamide, and two previously reported nonsteroidal androgens, S-1 and R-3. These studies provide the first crystallographic evidence of the mechanism by which nonsteroidal ligands interact with the wild type AR. We have shown that changes induced to the positions of Trp-741, Thr-877, and Met-895 allow for ligand accommodation within the AR binding pocket and that a water-mediated hydrogen bond to the backbone oxygen of Leu-873 and the ketone of hydroxyflutamide is present when bound to the T877A AR variant. Additionally, we demonstrated that R-bicalutamide stimulates transcriptional activation in AR harboring the M895T point mutation. As a whole, these studies provide critical new insight for receptor-based drug design of nonsteroidal AR agonists and antagonists.

-	~~==Disease==~~	+	Structural basis for accommodation of nonsteroidal ligands in the androgen receptor.,Bohl CE, Miller DD, Chen J, Bell CE, Dalton JT J Biol Chem. 2005 Nov 11;280(45):37747-54. Epub 2005 Aug 29. PMID:16129672<ref>PMID:16129672</ref>
-	~~[[http://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects~~ in ~~AR are~~ the cause of androgen insensitivity syndrome (AIS) [MIM:[http://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~~:~~[http://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:[http://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==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/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>

-	==~~About this Structure~~==	+	==See Also==
-	[[~~2ax7~~]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA].	+	*[[Androgen receptor\|Androgen receptor]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:016129672</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bell, C E.]]		[[Category: Bell, C E.]]

OCA at 20:34, 24 March 2013

2013-03-24T20:34:54Z

←Older revision		Revision as of 20:34, 24 March 2013
Line 1:		Line 1:
-	[[Image:2ax7.png\|left\|200px]]
-
	{{STRUCTURE_2ax7\| PDB=2ax7 \| SCENE= }}		{{STRUCTURE_2ax7\| PDB=2ax7 \| SCENE= }}
-
	===Crystal Structure Of The Androgen Receptor Ligand Binding Domain T877A Mutant In Complex With S-1===		===Crystal Structure Of The Androgen Receptor Ligand Binding Domain T877A Mutant In Complex With S-1===
		+	{{ABSTRACT_PUBMED_16129672}}

-	~~{{ABSTRACT_PUBMED_16129672}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/ANDR_HUMAN ANDR_HUMAN]] Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:[http://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:[http://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:[http://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==
		+	[[http://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>

	==About this Structure==		==About this Structure==
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	==Reference==		==Reference==
-	<ref group="xtra">PMID:016129672</ref><references group="xtra"/>	+	<ref group="xtra">PMID:016129672</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bell, C E.]]		[[Category: Bell, C E.]]

OCA: Protected "2ax7" [edit=sysop:move=sysop]

2013-01-06T10:50:17Z

Protected "2ax7" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:50, 6 January 2013

OCA at 10:50, 6 January 2013

2013-01-06T10:50:15Z

←Older revision		Revision as of 10:50, 6 January 2013
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-	{{Seed}}
	[[Image:2ax7.png\|left\|200px]]		[[Image:2ax7.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_2ax7\| PDB=2ax7 \| SCENE= }}		{{STRUCTURE_2ax7\| PDB=2ax7 \| SCENE= }}

	===Crystal Structure Of The Androgen Receptor Ligand Binding Domain T877A Mutant In Complex With S-1===		===Crystal Structure Of The Androgen Receptor Ligand Binding Domain T877A Mutant In Complex With S-1===

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-	<!--
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	{{ABSTRACT_PUBMED_16129672}}		{{ABSTRACT_PUBMED_16129672}}

	==About this Structure==		==About this Structure==
-	~~2AX7~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA].	+	[[2ax7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AX7 OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~16129672~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:016129672</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bell, C E.]]		[[Category: Bell, C E.]]
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	[[Category: Miller, D D.]]		[[Category: Miller, D D.]]
	[[Category: Transcription]]		[[Category: Transcription]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 02:25:34 2009''