1t65 - Revision history

OCA at 08:36, 14 February 2024

OCA — Wed, 14 Feb 2024 08:36:36 GMT

←Older revision		Revision as of 08:36, 14 February 2024
Line 3:		Line 3:
	<StructureSection load='1t65' size='340' side='right'caption='[[1t65]], [[Resolution\|resolution]] 1.66Å' scene=''>		<StructureSection load='1t65' size='340' side='right'caption='[[1t65]], [[Resolution\|resolution]] 1.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1t65]] is a 2 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=1T65 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1T65 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1t65]] is a 2 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=1T65 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T65 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=DHT:5~~-~~ALPHA-DIHYDROTESTOSTERONE'>DHT</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]] 1.66Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><~~div style~~='~~overflow~~: ~~auto; max~~-~~height: 3em;~~'>~~[[1t5z\|1t5z]], [[1t63\|1t63]]~~</~~div~~>~~</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NCOA2, TIF2 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [https://pdbe.org/1t65 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [https://www.ebi.ac.uk/pdbsum/1t65 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t65 ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [~~http~~://pdbe.org/1t65 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1t65 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1t65 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. [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.	+	[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> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</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]]
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	</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=1t65 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=1t65 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Androgens drive sex differentiation, bone and muscle development, and promote growth of hormone-dependent cancers by binding the nuclear androgen receptor (AR), which recruits coactivators to responsive genes. Most nuclear receptors recruit steroid receptor coactivators (SRCs) to their ligand binding domain (LBD) using a leucine-rich motif (LXXLL). AR is believed to recruit unique coactivators to its LBD using an aromatic-rich motif (FXXLF) while recruiting SRCs to its N-terminal domain (NTD) through an alternate mechanism. Here, we report that the AR-LBD interacts with both FXXLF motifs and a subset of LXXLL motifs and that contacts with these LXXLL motifs are both necessary and sufficient for SRC-mediated AR regulation of transcription. Crystal structures of the activated AR in complex with both recruitment motifs reveal that side chains unique to the AR-LBD rearrange to bind either the bulky FXXLF motifs or the more compact LXXLL motifs and that AR utilizes subsidiary contacts with LXXLL flanking sequences to discriminate between LXXLL motifs.
-
-	The molecular mechanisms of coactivator utilization in ligand-dependent transactivation by the androgen receptor.,Estebanez-Perpina E, Moore JM, Mar E, Delgado-Rodrigues E, Nguyen P, Baxter JD, Buehrer BM, Webb P, Fletterick RJ, Guy RK J Biol Chem. 2005 Mar 4;280(9):8060-8. Epub 2004 Nov 24. PMID:15563469<ref>PMID:15563469</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1t65" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Baxter~~, J D~~]]	+	[[Category: Baxter JD]]
-	[[Category: Delgado-Rodrigues, E]]	+	[[Category: Delgado-Rodrigues E]]
-	[[Category: Estebanez-Perpina, E]]	+	[[Category: Estebanez-Perpina E]]
-	[[Category: Fletterick~~, R J~~]]	+	[[Category: Fletterick RJ]]
-	[[Category: Guy~~, R K~~]]	+	[[Category: Guy RK]]
-	[[Category: Mar, E]]	+	[[Category: Mar E]]
-	[[Category: Moore~~, J M.R~~]]	+	[[Category: Moore JMR]]
-	[[Category: Nguyen, P]]	+	[[Category: Nguyen P]]
-	[[Category: Webb, P]]	+	[[Category: Webb P]]
-	~~[[Category: Androgen receptor ligand binding domain grip1 nr box2 coactivators crystal structure non-helical]]~~	+
-	~~[[Category: Hormone-growth factor complex~~]]	+

OCA at 11:43, 24 December 2020

OCA — Thu, 24 Dec 2020 11:43:22 GMT

←Older revision		Revision as of 11:43, 24 December 2020
Line 1:		Line 1:

	==Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation==		==Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation==
-	<StructureSection load='1t65' size='340' side='right' caption='[[1t65]], [[Resolution\|resolution]] 1.66Å' scene=''>	+	<StructureSection load='1t65' size='340' side='right'caption='[[1t65]], [[Resolution\|resolution]] 1.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1t65]] is a 2 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=1T65 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1T65 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1t65]] is a 2 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=1T65 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1T65 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1t5z\|1t5z]], [[1t63\|1t63]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1t5z\|1t5z]], [[1t63\|1t63]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NCOA2, TIF2 ([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, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NCOA2, TIF2 ([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=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [http://pdbe.org/1t65 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [http://www.ebi.ac.uk/pdbsum/1t65 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t65 ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [http://pdbe.org/1t65 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [http://www.ebi.ac.uk/pdbsum/1t65 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t65 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t6/1t65_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t6/1t65_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>
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	</div>		</div>
	<div class="pdbe-citations 1t65" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1t65" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Androgen receptor 3D structures\|Androgen receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Baxter, J D]]		[[Category: Baxter, J D]]
	[[Category: Delgado-Rodrigues, E]]		[[Category: Delgado-Rodrigues, E]]

OCA at 13:14, 12 October 2017

OCA — Thu, 12 Oct 2017 13:14:31 GMT

←Older revision		Revision as of 13:14, 12 October 2017
Line 1:		Line 1:
		+
	==Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation==		==Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation==
	<StructureSection load='1t65' size='340' side='right' caption='[[1t65]], [[Resolution\|resolution]] 1.66Å' scene=''>		<StructureSection load='1t65' size='340' side='right' caption='[[1t65]], [[Resolution\|resolution]] 1.66Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1t5z\|1t5z]], [[1t63\|1t63]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1t5z\|1t5z]], [[1t63\|1t63]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NCOA2, TIF2 ([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, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NCOA2, TIF2 ([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=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [http://pdbe.org/1t65 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [http://www.ebi.ac.uk/pdbsum/1t65 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=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [http://pdbe.org/1t65 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [http://www.ebi.ac.uk/pdbsum/1t65 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t65 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 31:		Line 32:
	</div>		</div>
	<div class="pdbe-citations 1t65" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1t65" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Androgen receptor\|Androgen receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 14:43, 7 February 2016

OCA — Sun, 07 Feb 2016 14:43:00 GMT

←Older revision		Revision as of 14:43, 7 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=1t65 ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 02:29, 10 September 2015

OCA — Thu, 10 Sep 2015 02:29:09 GMT

←Older revision		Revision as of 02:29, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='1t65' size='340' side='right' caption='[[1t65]], [[Resolution\|resolution]] 1.66Å' scene=''>		<StructureSection load='1t65' size='340' side='right' caption='[[1t65]], [[Resolution\|resolution]] 1.66Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1t65]] is a 2 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=1T65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T65 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1t65]] is a 2 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=1T65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T65 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1t5z\|1t5z]], [[1t63\|1t63]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1t5z\|1t5z]], [[1t63\|1t63]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), NCOA2, TIF2 ([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, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), NCOA2, TIF2 ([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=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [http://www.ebi.ac.uk/pdbsum/1t65 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=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [http://pdbe.org/1t65 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [http://www.ebi.ac.uk/pdbsum/1t65 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 1t65" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 37:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Baxter, J D]]		[[Category: Baxter, J D]]
	[[Category: Delgado-Rodrigues, E]]		[[Category: Delgado-Rodrigues, E]]

OCA at 06:55, 6 January 2015

OCA — Tue, 06 Jan 2015 06:55:52 GMT

←Older revision		Revision as of 06:55, 6 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1t65]] is a 2 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=1T65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T65 FirstGlance]. <br>		<table><tr><td colspan='2'>[[1t65]] is a 2 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=1T65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T65 FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1t5z\|1t5z]], [[1t63\|1t63]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1t5z\|1t5z]], [[1t63\|1t63]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), NCOA2, TIF2 ([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, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), NCOA2, TIF2 ([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=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [http://www.ebi.ac.uk/pdbsum/1t65 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=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [http://www.ebi.ac.uk/pdbsum/1t65 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/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.		[[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/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
Line 38:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Baxter, J D.]]	+	[[Category: Baxter, J D]]
-	[[Category: Delgado-Rodrigues, E.]]	+	[[Category: Delgado-Rodrigues, E]]
-	[[Category: Estebanez-Perpina, E.]]	+	[[Category: Estebanez-Perpina, E]]
-	[[Category: Fletterick, R J.]]	+	[[Category: Fletterick, R J]]
-	[[Category: Guy, R K.]]	+	[[Category: Guy, R K]]
-	[[Category: Mar, E.]]	+	[[Category: Mar, E]]
-	[[Category: Moore, J M.R.]]	+	[[Category: Moore, J M.R]]
-	[[Category: Nguyen, P.]]	+	[[Category: Nguyen, P]]
-	[[Category: Webb, P.]]	+	[[Category: Webb, P]]
	[[Category: Androgen receptor ligand binding domain grip1 nr box2 coactivators crystal structure non-helical]]		[[Category: Androgen receptor ligand binding domain grip1 nr box2 coactivators crystal structure non-helical]]
	[[Category: Hormone-growth factor complex]]		[[Category: Hormone-growth factor complex]]

OCA at 21:23, 29 September 2014

OCA — Mon, 29 Sep 2014 21:23:46 GMT

←Older revision		Revision as of 21:23, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1t65\| PDB=1t65 \| SCENE= }}~~	+	==Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation==
-	===Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation===	+	<StructureSection load='1t65' size='340' side='right' caption='[[1t65]], [[Resolution\|resolution]] 1.66Å' scene=''>
-	~~{{ABSTRACT_PUBMED_15563469}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1t65]] is a 2 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=1T65 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T65 FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DHT:5-ALPHA-DIHYDROTESTOSTERONE'>DHT</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1t5z\|1t5z]], [[1t63\|1t63]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">AR, NR3C4, DHTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), NCOA2, TIF2 ([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=1t65 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t65 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t65 RCSB], [http://www.ebi.ac.uk/pdbsum/1t65 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. [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
		+	== 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> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</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/t6/1t65_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 ==
		+	Androgens drive sex differentiation, bone and muscle development, and promote growth of hormone-dependent cancers by binding the nuclear androgen receptor (AR), which recruits coactivators to responsive genes. Most nuclear receptors recruit steroid receptor coactivators (SRCs) to their ligand binding domain (LBD) using a leucine-rich motif (LXXLL). AR is believed to recruit unique coactivators to its LBD using an aromatic-rich motif (FXXLF) while recruiting SRCs to its N-terminal domain (NTD) through an alternate mechanism. Here, we report that the AR-LBD interacts with both FXXLF motifs and a subset of LXXLL motifs and that contacts with these LXXLL motifs are both necessary and sufficient for SRC-mediated AR regulation of transcription. Crystal structures of the activated AR in complex with both recruitment motifs reveal that side chains unique to the AR-LBD rearrange to bind either the bulky FXXLF motifs or the more compact LXXLL motifs and that AR utilizes subsidiary contacts with LXXLL flanking sequences to discriminate between LXXLL motifs.

-	~~==Disease==~~	+	The molecular mechanisms of coactivator utilization in ligand-dependent transactivation by the androgen receptor.,Estebanez-Perpina E, Moore JM, Mar E, Delgado-Rodrigues E, Nguyen P, Baxter JD, Buehrer BM, Webb P, Fletterick RJ, Guy RK J Biol Chem. 2005 Mar 4;280(9):8060-8. Epub 2004 Nov 24. PMID:15563469<ref>PMID:15563469</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. [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.	+

-	~~==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> [[http://www~~.~~uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator~~ of ~~the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues~~.<~~ref~~>~~PMID:9430642~~</~~ref~~>	+	</div>

-	==~~About this Structure~~==	+	==See Also==
-	[[~~1t65~~]] is a 2 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=1T65 OCA].	+	*[[Androgen receptor\|Androgen receptor]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:015563469</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Baxter, J D.]]		[[Category: Baxter, J D.]]

OCA at 20:46, 24 March 2013

OCA — Sun, 24 Mar 2013 20:46:38 GMT

←Older revision		Revision as of 20:46, 24 March 2013
Line 1:		Line 1:
-	[[Image:1t65.png\|left\|200px]]
-
	{{STRUCTURE_1t65\| PDB=1t65 \| SCENE= }}		{{STRUCTURE_1t65\| PDB=1t65 \| SCENE= }}
-
	===Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation===		===Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation===
		+	{{ABSTRACT_PUBMED_15563469}}

-	~~{{ABSTRACT_PUBMED_15563469}}~~	+	==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/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
		+
		+	==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> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:015563469</ref><references group="xtra"/>	+	<ref group="xtra">PMID:015563469</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Baxter, J D.]]		[[Category: Baxter, J D.]]

OCA: Protected "1t65" [edit=sysop:move=sysop]

OCA — Sat, 05 Jan 2013 12:36:07 GMT

Protected "1t65" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:36, 5 January 2013

OCA at 12:36, 5 January 2013

OCA — Sat, 05 Jan 2013 12:36:05 GMT

←Older revision		Revision as of 12:36, 5 January 2013
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-	{{Seed}}
	[[Image:1t65.png\|left\|200px]]		[[Image:1t65.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_1t65", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
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	{{STRUCTURE_1t65\| PDB=1t65 \| SCENE= }}		{{STRUCTURE_1t65\| PDB=1t65 \| SCENE= }}

	===Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation===		===Crystal structure of the androgen receptor ligand binding domain with DHT and a peptide derived form its physiological coactivator GRIP1 NR box 2 bound in a non-helical conformation===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_15563469}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 15563469 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_15563469}}		{{ABSTRACT_PUBMED_15563469}}

	==About this Structure==		==About this Structure==
-	~~1T65~~ is a 2 ~~chains~~ structure ~~of sequences~~ 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=1T65 OCA].	+	[[1t65]] is a 2 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=1T65 OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~15563469~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:015563469</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Baxter, J D.]]		[[Category: Baxter, J D.]]
Line 35:		Line 23:
	[[Category: Webb, P.]]		[[Category: Webb, P.]]
	[[Category: Androgen receptor ligand binding domain grip1 nr box2 coactivators crystal structure non-helical]]		[[Category: Androgen receptor ligand binding domain grip1 nr box2 coactivators crystal structure non-helical]]
-		+	[[Category: Hormone-growth factor complex]]
-	~~''Page seeded by~~ [~~http~~:~~//oca.weizmann.ac.il/oca OCA~~ ] ~~on Mon Feb 16 14:32:23 2009''~~	+