1ich - Revision history

OCA at 08:34, 22 May 2024

OCA — Wed, 22 May 2024 08:34:08 GMT

←Older revision		Revision as of 08:34, 22 May 2024
Line 21:		Line 21:
	</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=1ich 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=1ich ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tumor necrosis factor receptor-1 death domain (TNFR-1 DD) is the intracellular functional domain responsible for the receptor signaling activities. The solution structure of the R347K mutant of TNFR-1 DD was solved by NMR spectroscopy. A total of 20 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 1167 distance constraints and 117 torsion angle constraints. The atomic rms distribution about the mean coordinate positions for the 20 structures for residues composing the secondary structure region is 0.40 A for the backbone atoms and 1.09 A for all atoms. The structure consists of six antiparallel alpha-helices arranged in a similar fashion to the other members of the death domain superfamily. The secondary structure and three-dimensional structure of R347K TNFR1-DD are very similar to the secondary structure and deduced topology of the R347A TNFR1-DD mutant. Mutagenesis studies identified critical residues located in alpha2 and part of alpha3 and alpha4 that are crucial for self-interaction and interaction with TRADD. Structural superposition with previously solved proteins in the death domain superfamily reveals that the major differences between the structures reside in alpha2, alpha3, and alpha4. Interestingly, these regions correspond to the binding sites of TNFR1-DD, providing a structural basis for the specificity of death domain interactions and its subsequent signaling event.
		+
		+	Solution structure of the tumor necrosis factor receptor-1 death domain.,Sukits SF, Lin LL, Hsu S, Malakian K, Powers R, Xu GY J Mol Biol. 2001 Jul 20;310(4):895-906. PMID:11453696<ref>PMID:11453696</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 1ich" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 07:46, 3 April 2024

OCA — Wed, 03 Apr 2024 07:46:16 GMT

←Older revision		Revision as of 07:46, 3 April 2024
Line 1:		Line 1:

	==SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN==		==SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN==
-	<StructureSection load='1ich' size='340' side='right'caption='[[1ich~~]], [[NMR_Ensembles_of_Models \| 1 NMR models~~]]' scene=''>	+	<StructureSection load='1ich' size='340' side='right'caption='[[1ich]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ICH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ICH FirstGlance]. <br>
-	</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [https://pdbe.org/1ich PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [https://www.ebi.ac.uk/pdbsum/1ich PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ich ProSAT]</span></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [https://pdbe.org/1ich PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [https://www.ebi.ac.uk/pdbsum/1ich PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ich ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:[https://omim.org/entry/142680 142680]]; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref> <ref>PMID:10902757</ref> <ref>PMID:11443543</ref> <ref>PMID:13130484</ref> <ref>PMID:14610673</ref> Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[https://omim.org/entry/614810 614810]]. A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Note=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.<ref>PMID:22801493</ref>	+	[https://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN] Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:[https://omim.org/entry/142680 142680]; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref> <ref>PMID:10902757</ref> <ref>PMID:11443543</ref> <ref>PMID:13130484</ref> <ref>PMID:14610673</ref> Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[https://omim.org/entry/614810 614810]. A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Note=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.<ref>PMID:22801493</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.	+	[https://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN] Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 20:		Line 21:
	</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=1ich 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=1ich ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Tumor necrosis factor receptor-1 death domain (TNFR-1 DD) is the intracellular functional domain responsible for the receptor signaling activities. The solution structure of the R347K mutant of TNFR-1 DD was solved by NMR spectroscopy. A total of 20 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 1167 distance constraints and 117 torsion angle constraints. The atomic rms distribution about the mean coordinate positions for the 20 structures for residues composing the secondary structure region is 0.40 A for the backbone atoms and 1.09 A for all atoms. The structure consists of six antiparallel alpha-helices arranged in a similar fashion to the other members of the death domain superfamily. The secondary structure and three-dimensional structure of R347K TNFR1-DD are very similar to the secondary structure and deduced topology of the R347A TNFR1-DD mutant. Mutagenesis studies identified critical residues located in alpha2 and part of alpha3 and alpha4 that are crucial for self-interaction and interaction with TRADD. Structural superposition with previously solved proteins in the death domain superfamily reveals that the major differences between the structures reside in alpha2, alpha3, and alpha4. Interestingly, these regions correspond to the binding sites of TNFR1-DD, providing a structural basis for the specificity of death domain interactions and its subsequent signaling event.
-
-	Solution structure of the tumor necrosis factor receptor-1 death domain.,Sukits SF, Lin LL, Hsu S, Malakian K, Powers R, Xu GY J Mol Biol. 2001 Jul 20;310(4):895-906. PMID:11453696<ref>PMID:11453696</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1ich" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Lin, L L]]	+	[[Category: Lin L-L]]
-	[[Category: Malakian, K]]	+	[[Category: Malakian K]]
-	[[Category: Powers, R]]	+	[[Category: Powers R]]
-	[[Category: Sukits~~, S F~~]]	+	[[Category: Sukits SF]]
-	[[Category: Xu, G Y]]	+	[[Category: Xu G-Y]]
-	~~[[Category: Apoptosis]]~~	+
-	~~[[Category: Death domain~~]]	+

OCA at 10:59, 4 August 2021

OCA — Wed, 04 Aug 2021 10:59:28 GMT

←Older revision		Revision as of 10:59, 4 August 2021
Line 3:		Line 3:
	<StructureSection load='1ich' size='340' side='right'caption='[[1ich]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>		<StructureSection load='1ich' size='340' side='right'caption='[[1ich]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1ICH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ICH FirstGlance]. <br>
-	</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [~~http~~://pdbe.org/1ich PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1ich PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1ich ProSAT]</span></td></tr>	+	</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [https://pdbe.org/1ich PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [https://www.ebi.ac.uk/pdbsum/1ich PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ich ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:[~~http~~://omim.org/entry/142680 142680]]; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref> <ref>PMID:10902757</ref> <ref>PMID:11443543</ref> <ref>PMID:13130484</ref> <ref>PMID:14610673</ref> Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[~~http~~://omim.org/entry/614810 614810]]. A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Note=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.<ref>PMID:22801493</ref>	+	[[https://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:[https://omim.org/entry/142680 142680]]; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref> <ref>PMID:10902757</ref> <ref>PMID:11443543</ref> <ref>PMID:13130484</ref> <ref>PMID:14610673</ref> Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[https://omim.org/entry/614810 614810]]. A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Note=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.<ref>PMID:22801493</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.	+	[[https://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 31:		Line 31:

	==See Also==		==See Also==
-	*[[Tumor necrosis factor receptor\|Tumor necrosis factor receptor]]	+	*[[Tumor necrosis factor receptor 3D structures\|Tumor necrosis factor receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:04, 30 October 2019

OCA — Wed, 30 Oct 2019 10:04:42 GMT

←Older revision		Revision as of 10:04, 30 October 2019
Line 1:		Line 1:

	==SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN==		==SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN==
-	<StructureSection load='1ich' size='340' side='right' caption='[[1ich]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>	+	<StructureSection load='1ich' size='340' side='right'caption='[[1ich]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ICH FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ICH FirstGlance]. <br>
Line 37:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Lin, L L]]		[[Category: Lin, L L]]
	[[Category: Malakian, K]]		[[Category: Malakian, K]]

OCA at 09:05, 10 January 2018

OCA — Wed, 10 Jan 2018 09:05:09 GMT

←Older revision		Revision as of 09:05, 10 January 2018
Line 1:		Line 1:
		+
	==SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN==		==SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN==
	<StructureSection load='1ich' size='340' side='right' caption='[[1ich]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>		<StructureSection load='1ich' size='340' side='right' caption='[[1ich]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ICH FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ICH FirstGlance]. <br>
-	</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [http://pdbe.org/1ich PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [http://www.ebi.ac.uk/pdbsum/1ich PDBsum]</span></td></tr>	+	</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [http://pdbe.org/1ich PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [http://www.ebi.ac.uk/pdbsum/1ich PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ich ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 13:		Line 14:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ic/1ich_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ic/1ich_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>

OCA at 20:16, 9 February 2016

OCA — Tue, 09 Feb 2016 20:16:38 GMT

←Older revision		Revision as of 20:16, 9 February 2016
Line 17:		Line 17:
	<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=1ich ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 01:40, 11 September 2015

OCA — Fri, 11 Sep 2015 01:40:32 GMT

←Older revision		Revision as of 01:40, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='1ich' size='340' side='right' caption='[[1ich]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>		<StructureSection load='1ich' size='340' side='right' caption='[[1ich]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ICH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ICH FirstGlance]. <br>
-	</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [http://www.ebi.ac.uk/pdbsum/1ich PDBsum]</span></td></tr>	+	</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [http://pdbe.org/1ich PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [http://www.ebi.ac.uk/pdbsum/1ich PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 27:		Line 27:
	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 1ich" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 34:		Line 35:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Lin, L L]]		[[Category: Lin, L L]]
	[[Category: Malakian, K]]		[[Category: Malakian, K]]

OCA at 09:43, 2 January 2015

OCA — Fri, 02 Jan 2015 09:43:20 GMT

←Older revision		Revision as of 09:43, 2 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ICH FirstGlance]. <br>		<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ICH FirstGlance]. <br>
-	</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [http://www.ebi.ac.uk/pdbsum/1ich PDBsum]</span></td></tr>	+	</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [http://www.ebi.ac.uk/pdbsum/1ich PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:[http://omim.org/entry/142680 142680]]; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref> <ref>PMID:10902757</ref> <ref>PMID:11443543</ref> <ref>PMID:13130484</ref> <ref>PMID:14610673</ref> Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[http://omim.org/entry/614810 614810]]. A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Note=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.<ref>PMID:22801493</ref>		[[http://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:[http://omim.org/entry/142680 142680]]; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref> <ref>PMID:10902757</ref> <ref>PMID:11443543</ref> <ref>PMID:13130484</ref> <ref>PMID:14610673</ref> Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[http://omim.org/entry/614810 614810]]. A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Note=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.<ref>PMID:22801493</ref>
Line 35:		Line 35:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Lin, L L.]]	+	[[Category: Lin, L L]]
-	[[Category: Malakian, K.]]	+	[[Category: Malakian, K]]
-	[[Category: Powers, R.]]	+	[[Category: Powers, R]]
-	[[Category: Sukits, S F.]]	+	[[Category: Sukits, S F]]
-	[[Category: Xu, G Y.]]	+	[[Category: Xu, G Y]]
	[[Category: Apoptosis]]		[[Category: Apoptosis]]
	[[Category: Death domain]]		[[Category: Death domain]]

OCA at 15:56, 29 September 2014

OCA — Mon, 29 Sep 2014 15:56:56 GMT

←Older revision		Revision as of 15:56, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1ich\| PDB=1ich \| SCENE= }}~~	+	==SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN==
-	===SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN===	+	<StructureSection load='1ich' size='340' side='right' caption='[[1ich]], [[NMR_Ensembles_of_Models \| 1 NMR models]]' scene=''>
-	~~{{ABSTRACT_PUBMED_11453696}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1ich]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ICH FirstGlance]. <br>
		+	</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=1ich FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ich OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1ich RCSB], [http://www.ebi.ac.uk/pdbsum/1ich PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:[http://omim.org/entry/142680 142680]]; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref> <ref>PMID:10902757</ref> <ref>PMID:11443543</ref> <ref>PMID:13130484</ref> <ref>PMID:14610673</ref> Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[http://omim.org/entry/614810 614810]]. A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Note=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.<ref>PMID:22801493</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.
		+	== 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/ic/1ich_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 ==
		+	Tumor necrosis factor receptor-1 death domain (TNFR-1 DD) is the intracellular functional domain responsible for the receptor signaling activities. The solution structure of the R347K mutant of TNFR-1 DD was solved by NMR spectroscopy. A total of 20 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 1167 distance constraints and 117 torsion angle constraints. The atomic rms distribution about the mean coordinate positions for the 20 structures for residues composing the secondary structure region is 0.40 A for the backbone atoms and 1.09 A for all atoms. The structure consists of six antiparallel alpha-helices arranged in a similar fashion to the other members of the death domain superfamily. The secondary structure and three-dimensional structure of R347K TNFR1-DD are very similar to the secondary structure and deduced topology of the R347A TNFR1-DD mutant. Mutagenesis studies identified critical residues located in alpha2 and part of alpha3 and alpha4 that are crucial for self-interaction and interaction with TRADD. Structural superposition with previously solved proteins in the death domain superfamily reveals that the major differences between the structures reside in alpha2, alpha3, and alpha4. Interestingly, these regions correspond to the binding sites of TNFR1-DD, providing a structural basis for the specificity of death domain interactions and its subsequent signaling event.

-	~~==Disease==~~	+	Solution structure of the tumor necrosis factor receptor-1 death domain.,Sukits SF, Lin LL, Hsu S, Malakian K, Powers R, Xu GY J Mol Biol. 2001 Jul 20;310(4):895-906. PMID:11453696<ref>PMID:11453696</ref>
-	~~[[http://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Defects in TNFRSF1A are~~ the ~~cause of familial hibernian fever (FHF) [MIM:[http://omim.org/entry/142680 142680]]; also known as~~ tumor necrosis factor receptor-~~associated periodic syndrome (TRAPS)~~. ~~FHF is a hereditary periodic fever syndrome characterized by recurrent fever~~, ~~abdominal pain~~, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref><ref>PMID:10902757</ref><ref>PMID:11443543</ref><ref>PMID:13130484</ref><ref>PMID:14610673</ref> Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[http://omim.org/entry/614810 614810]]. A multifactorial, ~~inflammatory~~, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, ~~mediated by both cellular and humoral immunity. Clinical manifestations include visual loss~~, ~~extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction~~. ~~Genetic and environmental factors influence susceptibility to the disease. Note=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform~~ 4 ~~a transcript encoding a C~~-~~terminally truncated protein which is secreted and may function as a TNF antagonist~~.<ref>PMID:~~22801493~~</ref>	+
-		+
-	~~==Function==~~	+
-	[[http://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[1ich]] is~~ a ~~1 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full experimental information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=1ICH OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:011453696</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Tumor necrosis factor receptor\|Tumor necrosis factor receptor]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Lin, L L.]]		[[Category: Lin, L L.]]

OCA at 18:25, 24 March 2013

OCA — Sun, 24 Mar 2013 18:25:38 GMT

←Older revision		Revision as of 18:25, 24 March 2013
Line 1:		Line 1:
-	[[Image:1ich.png\|left\|200px]]
-
	{{STRUCTURE_1ich\| PDB=1ich \| SCENE= }}		{{STRUCTURE_1ich\| PDB=1ich \| SCENE= }}
-
	===SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN===		===SOLUTION STRUCTURE OF THE TUMOR NECROSIS FACTOR RECEPTOR-1 DEATH DOMAIN===
		+	{{ABSTRACT_PUBMED_11453696}}

-	~~{{ABSTRACT_PUBMED_11453696}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Defects in TNFRSF1A are the cause of familial hibernian fever (FHF) [MIM:[http://omim.org/entry/142680 142680]]; also known as tumor necrosis factor receptor-associated periodic syndrome (TRAPS). FHF is a hereditary periodic fever syndrome characterized by recurrent fever, abdominal pain, localized tender skin lesions and myalgia. Reactive amyloidosis is the main complication and occurs in 25% of cases.<ref>PMID:10199409</ref><ref>PMID:10902757</ref><ref>PMID:11443543</ref><ref>PMID:13130484</ref><ref>PMID:14610673</ref> Genetic variation in TNFRSF1A is associated with susceptibility to multiple sclerosis 5 (MS5) [MIM:[http://omim.org/entry/614810 614810]]. A multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheat, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease. Note=An intronic mutation affecting alternative splicing and skipping of exon 6 directs increased expression of isoform 4 a transcript encoding a C-terminally truncated protein which is secreted and may function as a TNF antagonist.<ref>PMID:22801493</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/TNR1A_HUMAN TNR1A_HUMAN]] Receptor for TNFSF2/TNF-alpha and homotrimeric TNFSF1/lymphotoxin-alpha. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Contributes to the induction of non-cytocidal TNF effects including anti-viral state and activation of the acid sphingomyelinase.

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

	==Reference==		==Reference==
-	<ref group="xtra">PMID:011453696</ref><references group="xtra"/>	+	<ref group="xtra">PMID:011453696</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Lin, L L.]]		[[Category: Lin, L L.]]