3gef - Revision history

OCA at 07:04, 6 September 2023

2023-09-06T07:04:17Z

←Older revision		Revision as of 07:04, 6 September 2023
Line 3:		Line 3:
	<StructureSection load='3gef' size='340' side='right'caption='[[3gef]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='3gef' size='340' side='right'caption='[[3gef]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3gef]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GEF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3gef]] is a 4 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=3GEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GEF FirstGlance]. <br>
-	</td></tr><tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=CSD:3~~-~~SULFINOALANINE'>CSD</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]] 1.5Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~Lamin A/C 435~~-~~552, LMN1, LMNA ([https:~~/~~/www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gef OCA], [https://pdbe.org/3gef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gef RCSB], [https://www.ebi.ac.uk/pdbsum/3gef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gef ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gef OCA], [https://pdbe.org/3gef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gef RCSB], [https://www.ebi.ac.uk/pdbsum/3gef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gef ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 2, autosomal dominant (EDMD2) [MIM:[https://omim.org/entry/181350 181350]]. A degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.<ref>PMID:19933576</ref> <ref>PMID:10080180</ref> <ref>PMID:10739764</ref> <ref>PMID:10939567</ref> <ref>PMID:10908904</ref> <ref>PMID:11503164</ref> <ref>PMID:11792809</ref> <ref>PMID:12032588</ref> <ref>PMID:14684700</ref> <ref>PMID:12649505</ref> <ref>PMID:14985400</ref> <ref>PMID:15744034</ref> <ref>PMID:20848652</ref> Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 3, autosomal recessive (EDMD3) [MIM:[https://omim.org/entry/181350 181350]]. Defects in LMNA are the cause of cardiomyopathy dilated type 1A (CMD1A) [MIM:[https://omim.org/entry/115200 115200]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:18606848</ref> <ref>PMID:11792809</ref> <ref>PMID:14684700</ref> <ref>PMID:10580070</ref> <ref>PMID:11561226</ref> <ref>PMID:12486434</ref> <ref>PMID:11897440</ref> <ref>PMID:12628721</ref> <ref>PMID:12920062</ref> <ref>PMID:15219508</ref> <ref>PMID:15140538</ref> <ref>PMID:16061563</ref> <ref>PMID:21846512</ref> Defects in LMNA are the cause of familial partial lipodystrophy type 2 (FPLD2) [MIM:[https://omim.org/entry/151660 151660]]; also known as familial partial lipodystrophy Dunnigan type. A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol.<ref>PMID:11792809</ref> <ref>PMID:10739751</ref> <ref>PMID:10587585</ref> <ref>PMID:10655060</ref> <ref>PMID:12015247</ref> <ref>PMID:12196663</ref> <ref>PMID:12629077</ref> <ref>PMID:17250669</ref> Defects in LMNA are the cause of limb-girdle muscular dystrophy type 1B (LGMD1B) [MIM:[https://omim.org/entry/159001 159001]]. LGMD1B is an autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances, dilated cardiomyopathy, and the absence of early contractures. LGMD1B is characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes.<ref>PMID:12032588</ref> <ref>PMID:15744034</ref> <ref>PMID:10814726</ref> <ref>PMID:11525883</ref> <ref>PMID:12673789</ref> <ref>PMID:17136397</ref> Defects in LMNA are the cause of Charcot-Marie-Tooth disease type 2B1 (CMT2B1) [MIM:[https://omim.org/entry/605588 605588]]. CMT2B1 is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2B1 inheritance is autosomal recessive.<ref>PMID:11799477</ref> Defects in LMNA are the cause of Hutchinson-Gilford progeria syndrome (HGPS) [MIM:[https://omim.org/entry/176670 176670]]. HGPS is a rare genetic disorder characterized by features reminiscent of marked premature aging. Note=HGPS is caused by the toxic accumulation of a mutant form of lamin-A/C. This mutant protein, called progerin, acts to deregulate mitosis and DNA damage signaling, leading to premature cell death and senescence. Progerin lacks the conserved ZMPSTE24/FACE1 cleavage site and therefore remains permanently farnesylated. Thus, although it can enter the nucleus and associate with the nuclear envelope, it cannot incorporate normally into the nuclear lamina.<ref>PMID:19933576</ref> <ref>PMID:12768443</ref> <ref>PMID:12927431</ref> <ref>PMID:12714972</ref> <ref>PMID:15286156</ref> <ref>PMID:15622532</ref> Defects in LMNA are the cause of cardiomyopathy dilated with hypergonadotropic hypogonadism (CMDHH) [MIM:[https://omim.org/entry/212112 212112]]. A disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including mental retardation, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Defects in LMNA are the cause of mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:[https://omim.org/entry/248370 248370]]. A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroide appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased.<ref>PMID:12075506</ref> <ref>PMID:15998779</ref> <ref>PMID:16278265</ref> Defects in LMNA are a cause of lethal tight skin contracture syndrome (LTSCS) [MIM:[https://omim.org/entry/275210 275210]]; also known as restrictive dermopathy (RD). Lethal tight skin contracture syndrome is a rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance.<ref>PMID:15317753</ref> Defects in LMNA are the cause of heart-hand syndrome Slovenian type (HHS-Slovenian) [MIM:[https://omim.org/entry/610140 610140]]. Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations. Defects in LMNA are the cause of muscular dystrophy congenital LMNA-related (MDCL) [MIM:[https://omim.org/entry/613205 613205]]. It is a form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures.<ref>PMID:18551513</ref>	+	[https://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN] Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 2, autosomal dominant (EDMD2) [MIM:[https://omim.org/entry/181350 181350]. A degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.<ref>PMID:19933576</ref> <ref>PMID:10080180</ref> <ref>PMID:10739764</ref> <ref>PMID:10939567</ref> <ref>PMID:10908904</ref> <ref>PMID:11503164</ref> <ref>PMID:11792809</ref> <ref>PMID:12032588</ref> <ref>PMID:14684700</ref> <ref>PMID:12649505</ref> <ref>PMID:14985400</ref> <ref>PMID:15744034</ref> <ref>PMID:20848652</ref> Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 3, autosomal recessive (EDMD3) [MIM:[https://omim.org/entry/181350 181350]. Defects in LMNA are the cause of cardiomyopathy dilated type 1A (CMD1A) [MIM:[https://omim.org/entry/115200 115200]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:18606848</ref> <ref>PMID:11792809</ref> <ref>PMID:14684700</ref> <ref>PMID:10580070</ref> <ref>PMID:11561226</ref> <ref>PMID:12486434</ref> <ref>PMID:11897440</ref> <ref>PMID:12628721</ref> <ref>PMID:12920062</ref> <ref>PMID:15219508</ref> <ref>PMID:15140538</ref> <ref>PMID:16061563</ref> <ref>PMID:21846512</ref> Defects in LMNA are the cause of familial partial lipodystrophy type 2 (FPLD2) [MIM:[https://omim.org/entry/151660 151660]; also known as familial partial lipodystrophy Dunnigan type. A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol.<ref>PMID:11792809</ref> <ref>PMID:10739751</ref> <ref>PMID:10587585</ref> <ref>PMID:10655060</ref> <ref>PMID:12015247</ref> <ref>PMID:12196663</ref> <ref>PMID:12629077</ref> <ref>PMID:17250669</ref> Defects in LMNA are the cause of limb-girdle muscular dystrophy type 1B (LGMD1B) [MIM:[https://omim.org/entry/159001 159001]. LGMD1B is an autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances, dilated cardiomyopathy, and the absence of early contractures. LGMD1B is characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes.<ref>PMID:12032588</ref> <ref>PMID:15744034</ref> <ref>PMID:10814726</ref> <ref>PMID:11525883</ref> <ref>PMID:12673789</ref> <ref>PMID:17136397</ref> Defects in LMNA are the cause of Charcot-Marie-Tooth disease type 2B1 (CMT2B1) [MIM:[https://omim.org/entry/605588 605588]. CMT2B1 is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2B1 inheritance is autosomal recessive.<ref>PMID:11799477</ref> Defects in LMNA are the cause of Hutchinson-Gilford progeria syndrome (HGPS) [MIM:[https://omim.org/entry/176670 176670]. HGPS is a rare genetic disorder characterized by features reminiscent of marked premature aging. Note=HGPS is caused by the toxic accumulation of a mutant form of lamin-A/C. This mutant protein, called progerin, acts to deregulate mitosis and DNA damage signaling, leading to premature cell death and senescence. Progerin lacks the conserved ZMPSTE24/FACE1 cleavage site and therefore remains permanently farnesylated. Thus, although it can enter the nucleus and associate with the nuclear envelope, it cannot incorporate normally into the nuclear lamina.<ref>PMID:19933576</ref> <ref>PMID:12768443</ref> <ref>PMID:12927431</ref> <ref>PMID:12714972</ref> <ref>PMID:15286156</ref> <ref>PMID:15622532</ref> Defects in LMNA are the cause of cardiomyopathy dilated with hypergonadotropic hypogonadism (CMDHH) [MIM:[https://omim.org/entry/212112 212112]. A disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including mental retardation, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Defects in LMNA are the cause of mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:[https://omim.org/entry/248370 248370]. A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroide appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased.<ref>PMID:12075506</ref> <ref>PMID:15998779</ref> <ref>PMID:16278265</ref> Defects in LMNA are a cause of lethal tight skin contracture syndrome (LTSCS) [MIM:[https://omim.org/entry/275210 275210]; also known as restrictive dermopathy (RD). Lethal tight skin contracture syndrome is a rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance.<ref>PMID:15317753</ref> Defects in LMNA are the cause of heart-hand syndrome Slovenian type (HHS-Slovenian) [MIM:[https://omim.org/entry/610140 610140]. Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations. Defects in LMNA are the cause of muscular dystrophy congenital LMNA-related (MDCL) [MIM:[https://omim.org/entry/613205 613205]. It is a form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures.<ref>PMID:18551513</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics.<ref>PMID:20079404</ref> <ref>PMID:20458013</ref> Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.<ref>PMID:20079404</ref> <ref>PMID:20458013</ref>	+	[https://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN] Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics.<ref>PMID:20079404</ref> <ref>PMID:20458013</ref> Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.<ref>PMID:20079404</ref> <ref>PMID:20458013</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 35:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kozlov, S]]	+	[[Category: Kozlov S]]
-	[[Category: Magracheva, E]]	+	[[Category: Magracheva E]]
-	[[Category: Stuart, C]]	+	[[Category: Stuart C]]
-	[[Category: Wlodawer, A]]	+	[[Category: Wlodawer A]]
-	[[Category: Zdanov, A]]	+	[[Category: Zdanov A]]
-	~~[[Category: Cardiomyopathy]]~~	+
-	~~[[Category: Charcot-marie-tooth disease]]~~	+
-	~~[[Category: Disease mutation]]~~	+
-	~~[[Category: Immunoglobulin fold]]~~	+
-	~~[[Category: Intermediate filament]]~~	+
-	~~[[Category: Lamin]]~~	+
-	~~[[Category: Limb-girdle muscular dystrophy]]~~	+
-	~~[[Category: Lipoprotein]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Prenylation]]~~	+
-	~~[[Category: Structural protein~~]]	+

OCA at 20:05, 20 October 2021

2021-10-20T20:05:40Z

←Older revision		Revision as of 20:05, 20 October 2021
Line 1:		Line 1:

	==Crystal structure of the R482W mutant of lamin A/C==		==Crystal structure of the R482W mutant of lamin A/C==
-	<StructureSection load='3gef' size='340' side='right' caption='[[3gef]], [[Resolution\|resolution]] 1.50Å' scene=''>	+	<StructureSection load='3gef' size='340' side='right'caption='[[3gef]], [[Resolution\|resolution]] 1.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3gef]] is a 4 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=3GEF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3GEF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3gef]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GEF FirstGlance]. <br>
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Lamin A/C 435-552, LMN1, LMNA ([~~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">Lamin A/C 435-552, LMN1, LMNA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3gef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gef OCA], [~~http~~://pdbe.org/3gef PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3gef RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3gef PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3gef ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3gef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gef OCA], [https://pdbe.org/3gef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gef RCSB], [https://www.ebi.ac.uk/pdbsum/3gef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gef ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 2, autosomal dominant (EDMD2) [MIM:[~~http~~://omim.org/entry/181350 181350]]. A degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.<ref>PMID:19933576</ref> <ref>PMID:10080180</ref> <ref>PMID:10739764</ref> <ref>PMID:10939567</ref> <ref>PMID:10908904</ref> <ref>PMID:11503164</ref> <ref>PMID:11792809</ref> <ref>PMID:12032588</ref> <ref>PMID:14684700</ref> <ref>PMID:12649505</ref> <ref>PMID:14985400</ref> <ref>PMID:15744034</ref> <ref>PMID:20848652</ref> Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 3, autosomal recessive (EDMD3) [MIM:[~~http~~://omim.org/entry/181350 181350]]. Defects in LMNA are the cause of cardiomyopathy dilated type 1A (CMD1A) [MIM:[~~http~~://omim.org/entry/115200 115200]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:18606848</ref> <ref>PMID:11792809</ref> <ref>PMID:14684700</ref> <ref>PMID:10580070</ref> <ref>PMID:11561226</ref> <ref>PMID:12486434</ref> <ref>PMID:11897440</ref> <ref>PMID:12628721</ref> <ref>PMID:12920062</ref> <ref>PMID:15219508</ref> <ref>PMID:15140538</ref> <ref>PMID:16061563</ref> <ref>PMID:21846512</ref> Defects in LMNA are the cause of familial partial lipodystrophy type 2 (FPLD2) [MIM:[~~http~~://omim.org/entry/151660 151660]]; also known as familial partial lipodystrophy Dunnigan type. A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol.<ref>PMID:11792809</ref> <ref>PMID:10739751</ref> <ref>PMID:10587585</ref> <ref>PMID:10655060</ref> <ref>PMID:12015247</ref> <ref>PMID:12196663</ref> <ref>PMID:12629077</ref> <ref>PMID:17250669</ref> Defects in LMNA are the cause of limb-girdle muscular dystrophy type 1B (LGMD1B) [MIM:[~~http~~://omim.org/entry/159001 159001]]. LGMD1B is an autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances, dilated cardiomyopathy, and the absence of early contractures. LGMD1B is characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes.<ref>PMID:12032588</ref> <ref>PMID:15744034</ref> <ref>PMID:10814726</ref> <ref>PMID:11525883</ref> <ref>PMID:12673789</ref> <ref>PMID:17136397</ref> Defects in LMNA are the cause of Charcot-Marie-Tooth disease type 2B1 (CMT2B1) [MIM:[~~http~~://omim.org/entry/605588 605588]]. CMT2B1 is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2B1 inheritance is autosomal recessive.<ref>PMID:11799477</ref> Defects in LMNA are the cause of Hutchinson-Gilford progeria syndrome (HGPS) [MIM:[~~http~~://omim.org/entry/176670 176670]]. HGPS is a rare genetic disorder characterized by features reminiscent of marked premature aging. Note=HGPS is caused by the toxic accumulation of a mutant form of lamin-A/C. This mutant protein, called progerin, acts to deregulate mitosis and DNA damage signaling, leading to premature cell death and senescence. Progerin lacks the conserved ZMPSTE24/FACE1 cleavage site and therefore remains permanently farnesylated. Thus, although it can enter the nucleus and associate with the nuclear envelope, it cannot incorporate normally into the nuclear lamina.<ref>PMID:19933576</ref> <ref>PMID:12768443</ref> <ref>PMID:12927431</ref> <ref>PMID:12714972</ref> <ref>PMID:15286156</ref> <ref>PMID:15622532</ref> Defects in LMNA are the cause of cardiomyopathy dilated with hypergonadotropic hypogonadism (CMDHH) [MIM:[~~http~~://omim.org/entry/212112 212112]]. A disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including mental retardation, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Defects in LMNA are the cause of mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:[~~http~~://omim.org/entry/248370 248370]]. A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroide appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased.<ref>PMID:12075506</ref> <ref>PMID:15998779</ref> <ref>PMID:16278265</ref> Defects in LMNA are a cause of lethal tight skin contracture syndrome (LTSCS) [MIM:[~~http~~://omim.org/entry/275210 275210]]; also known as restrictive dermopathy (RD). Lethal tight skin contracture syndrome is a rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance.<ref>PMID:15317753</ref> Defects in LMNA are the cause of heart-hand syndrome Slovenian type (HHS-Slovenian) [MIM:[~~http~~://omim.org/entry/610140 610140]]. Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations. Defects in LMNA are the cause of muscular dystrophy congenital LMNA-related (MDCL) [MIM:[~~http~~://omim.org/entry/613205 613205]]. It is a form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures.<ref>PMID:18551513</ref>	+	[[https://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 2, autosomal dominant (EDMD2) [MIM:[https://omim.org/entry/181350 181350]]. A degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.<ref>PMID:19933576</ref> <ref>PMID:10080180</ref> <ref>PMID:10739764</ref> <ref>PMID:10939567</ref> <ref>PMID:10908904</ref> <ref>PMID:11503164</ref> <ref>PMID:11792809</ref> <ref>PMID:12032588</ref> <ref>PMID:14684700</ref> <ref>PMID:12649505</ref> <ref>PMID:14985400</ref> <ref>PMID:15744034</ref> <ref>PMID:20848652</ref> Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 3, autosomal recessive (EDMD3) [MIM:[https://omim.org/entry/181350 181350]]. Defects in LMNA are the cause of cardiomyopathy dilated type 1A (CMD1A) [MIM:[https://omim.org/entry/115200 115200]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:18606848</ref> <ref>PMID:11792809</ref> <ref>PMID:14684700</ref> <ref>PMID:10580070</ref> <ref>PMID:11561226</ref> <ref>PMID:12486434</ref> <ref>PMID:11897440</ref> <ref>PMID:12628721</ref> <ref>PMID:12920062</ref> <ref>PMID:15219508</ref> <ref>PMID:15140538</ref> <ref>PMID:16061563</ref> <ref>PMID:21846512</ref> Defects in LMNA are the cause of familial partial lipodystrophy type 2 (FPLD2) [MIM:[https://omim.org/entry/151660 151660]]; also known as familial partial lipodystrophy Dunnigan type. A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol.<ref>PMID:11792809</ref> <ref>PMID:10739751</ref> <ref>PMID:10587585</ref> <ref>PMID:10655060</ref> <ref>PMID:12015247</ref> <ref>PMID:12196663</ref> <ref>PMID:12629077</ref> <ref>PMID:17250669</ref> Defects in LMNA are the cause of limb-girdle muscular dystrophy type 1B (LGMD1B) [MIM:[https://omim.org/entry/159001 159001]]. LGMD1B is an autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances, dilated cardiomyopathy, and the absence of early contractures. LGMD1B is characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes.<ref>PMID:12032588</ref> <ref>PMID:15744034</ref> <ref>PMID:10814726</ref> <ref>PMID:11525883</ref> <ref>PMID:12673789</ref> <ref>PMID:17136397</ref> Defects in LMNA are the cause of Charcot-Marie-Tooth disease type 2B1 (CMT2B1) [MIM:[https://omim.org/entry/605588 605588]]. CMT2B1 is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2B1 inheritance is autosomal recessive.<ref>PMID:11799477</ref> Defects in LMNA are the cause of Hutchinson-Gilford progeria syndrome (HGPS) [MIM:[https://omim.org/entry/176670 176670]]. HGPS is a rare genetic disorder characterized by features reminiscent of marked premature aging. Note=HGPS is caused by the toxic accumulation of a mutant form of lamin-A/C. This mutant protein, called progerin, acts to deregulate mitosis and DNA damage signaling, leading to premature cell death and senescence. Progerin lacks the conserved ZMPSTE24/FACE1 cleavage site and therefore remains permanently farnesylated. Thus, although it can enter the nucleus and associate with the nuclear envelope, it cannot incorporate normally into the nuclear lamina.<ref>PMID:19933576</ref> <ref>PMID:12768443</ref> <ref>PMID:12927431</ref> <ref>PMID:12714972</ref> <ref>PMID:15286156</ref> <ref>PMID:15622532</ref> Defects in LMNA are the cause of cardiomyopathy dilated with hypergonadotropic hypogonadism (CMDHH) [MIM:[https://omim.org/entry/212112 212112]]. A disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including mental retardation, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Defects in LMNA are the cause of mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:[https://omim.org/entry/248370 248370]]. A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroide appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased.<ref>PMID:12075506</ref> <ref>PMID:15998779</ref> <ref>PMID:16278265</ref> Defects in LMNA are a cause of lethal tight skin contracture syndrome (LTSCS) [MIM:[https://omim.org/entry/275210 275210]]; also known as restrictive dermopathy (RD). Lethal tight skin contracture syndrome is a rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance.<ref>PMID:15317753</ref> Defects in LMNA are the cause of heart-hand syndrome Slovenian type (HHS-Slovenian) [MIM:[https://omim.org/entry/610140 610140]]. Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations. Defects in LMNA are the cause of muscular dystrophy congenital LMNA-related (MDCL) [MIM:[https://omim.org/entry/613205 613205]]. It is a form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures.<ref>PMID:18551513</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics.<ref>PMID:20079404</ref> <ref>PMID:20458013</ref> Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.<ref>PMID:20079404</ref> <ref>PMID:20458013</ref>	+	[[https://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics.<ref>PMID:20079404</ref> <ref>PMID:20458013</ref> Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.<ref>PMID:20079404</ref> <ref>PMID:20458013</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 36:		Line 36:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Kozlov, S]]		[[Category: Kozlov, S]]
	[[Category: Magracheva, E]]		[[Category: Magracheva, E]]

OCA at 05:16, 7 December 2018

2018-12-07T05:16:30Z

←Older revision		Revision as of 05:16, 7 December 2018
Line 1:		Line 1:
		+
	==Crystal structure of the R482W mutant of lamin A/C==		==Crystal structure of the R482W mutant of lamin A/C==
	<StructureSection load='3gef' size='340' side='right' caption='[[3gef]], [[Resolution\|resolution]] 1.50Å' scene=''>		<StructureSection load='3gef' size='340' side='right' caption='[[3gef]], [[Resolution\|resolution]] 1.50Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Lamin A/C 435-552, LMN1, LMNA ([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">Lamin A/C 435-552, LMN1, LMNA ([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=3gef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gef OCA], [http://pdbe.org/3gef PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gef RCSB], [http://www.ebi.ac.uk/pdbsum/3gef 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=3gef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gef OCA], [http://pdbe.org/3gef PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gef RCSB], [http://www.ebi.ac.uk/pdbsum/3gef PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gef ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ge/3gef_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ge/3gef_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 03:57, 9 February 2016

2016-02-09T03:57:16Z

←Older revision		Revision as of 03:57, 9 February 2016
Line 5:		Line 5:
	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>		</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Lamin A/C 435-552, LMN1, LMNA ([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">Lamin A/C 435-552, LMN1, LMNA ([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=3gef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gef OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gef RCSB], [http://www.ebi.ac.uk/pdbsum/3gef 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=3gef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gef OCA], [http://pdbe.org/3gef PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gef RCSB], [http://www.ebi.ac.uk/pdbsum/3gef PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 19:
	<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=3gef ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 29:
	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 3gef" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:30, 19 November 2014

2014-11-19T10:30:50Z

←Older revision		Revision as of 10:30, 19 November 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3gef\| PDB~~=3gef \| ~~SCENE~~= }}	+	==Crystal structure of the R482W mutant of lamin A/C==
-	===~~Crystal~~ structure of the ~~R482W~~ mutant of lamin A/C===	+	<StructureSection load='3gef' size='340' side='right' caption='[[3gef]], [[Resolution\|resolution]] 1.50Å' scene=''>
-	~~{{ABSTRACT_PUBMED_19574635}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3gef]] is a 4 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=3GEF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GEF FirstGlance]. <br>
		+	</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Lamin A/C 435-552, LMN1, LMNA ([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=3gef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gef OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gef RCSB], [http://www.ebi.ac.uk/pdbsum/3gef PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 2, autosomal dominant (EDMD2) [MIM:[http://omim.org/entry/181350 181350]]. A degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.<ref>PMID:19933576</ref> <ref>PMID:10080180</ref> <ref>PMID:10739764</ref> <ref>PMID:10939567</ref> <ref>PMID:10908904</ref> <ref>PMID:11503164</ref> <ref>PMID:11792809</ref> <ref>PMID:12032588</ref> <ref>PMID:14684700</ref> <ref>PMID:12649505</ref> <ref>PMID:14985400</ref> <ref>PMID:15744034</ref> <ref>PMID:20848652</ref> Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 3, autosomal recessive (EDMD3) [MIM:[http://omim.org/entry/181350 181350]]. Defects in LMNA are the cause of cardiomyopathy dilated type 1A (CMD1A) [MIM:[http://omim.org/entry/115200 115200]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:18606848</ref> <ref>PMID:11792809</ref> <ref>PMID:14684700</ref> <ref>PMID:10580070</ref> <ref>PMID:11561226</ref> <ref>PMID:12486434</ref> <ref>PMID:11897440</ref> <ref>PMID:12628721</ref> <ref>PMID:12920062</ref> <ref>PMID:15219508</ref> <ref>PMID:15140538</ref> <ref>PMID:16061563</ref> <ref>PMID:21846512</ref> Defects in LMNA are the cause of familial partial lipodystrophy type 2 (FPLD2) [MIM:[http://omim.org/entry/151660 151660]]; also known as familial partial lipodystrophy Dunnigan type. A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol.<ref>PMID:11792809</ref> <ref>PMID:10739751</ref> <ref>PMID:10587585</ref> <ref>PMID:10655060</ref> <ref>PMID:12015247</ref> <ref>PMID:12196663</ref> <ref>PMID:12629077</ref> <ref>PMID:17250669</ref> Defects in LMNA are the cause of limb-girdle muscular dystrophy type 1B (LGMD1B) [MIM:[http://omim.org/entry/159001 159001]]. LGMD1B is an autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances, dilated cardiomyopathy, and the absence of early contractures. LGMD1B is characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes.<ref>PMID:12032588</ref> <ref>PMID:15744034</ref> <ref>PMID:10814726</ref> <ref>PMID:11525883</ref> <ref>PMID:12673789</ref> <ref>PMID:17136397</ref> Defects in LMNA are the cause of Charcot-Marie-Tooth disease type 2B1 (CMT2B1) [MIM:[http://omim.org/entry/605588 605588]]. CMT2B1 is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2B1 inheritance is autosomal recessive.<ref>PMID:11799477</ref> Defects in LMNA are the cause of Hutchinson-Gilford progeria syndrome (HGPS) [MIM:[http://omim.org/entry/176670 176670]]. HGPS is a rare genetic disorder characterized by features reminiscent of marked premature aging. Note=HGPS is caused by the toxic accumulation of a mutant form of lamin-A/C. This mutant protein, called progerin, acts to deregulate mitosis and DNA damage signaling, leading to premature cell death and senescence. Progerin lacks the conserved ZMPSTE24/FACE1 cleavage site and therefore remains permanently farnesylated. Thus, although it can enter the nucleus and associate with the nuclear envelope, it cannot incorporate normally into the nuclear lamina.<ref>PMID:19933576</ref> <ref>PMID:12768443</ref> <ref>PMID:12927431</ref> <ref>PMID:12714972</ref> <ref>PMID:15286156</ref> <ref>PMID:15622532</ref> Defects in LMNA are the cause of cardiomyopathy dilated with hypergonadotropic hypogonadism (CMDHH) [MIM:[http://omim.org/entry/212112 212112]]. A disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including mental retardation, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Defects in LMNA are the cause of mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:[http://omim.org/entry/248370 248370]]. A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroide appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased.<ref>PMID:12075506</ref> <ref>PMID:15998779</ref> <ref>PMID:16278265</ref> Defects in LMNA are a cause of lethal tight skin contracture syndrome (LTSCS) [MIM:[http://omim.org/entry/275210 275210]]; also known as restrictive dermopathy (RD). Lethal tight skin contracture syndrome is a rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance.<ref>PMID:15317753</ref> Defects in LMNA are the cause of heart-hand syndrome Slovenian type (HHS-Slovenian) [MIM:[http://omim.org/entry/610140 610140]]. Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations. Defects in LMNA are the cause of muscular dystrophy congenital LMNA-related (MDCL) [MIM:[http://omim.org/entry/613205 613205]]. It is a form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures.<ref>PMID:18551513</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics.<ref>PMID:20079404</ref> <ref>PMID:20458013</ref> Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.<ref>PMID:20079404</ref> <ref>PMID:20458013</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/ge/3gef_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 ==
		+	Proteins of the A-type lamin family, which consists of two members, lamin A and lamin C, are the major components of a thin proteinaceous filamentous meshwork, the lamina, that underlies the inner nuclear membrane. A-type lamins have recently become the focus of extensive functional studies as a consequence of the linking of at least eight congenital diseases to mutations in the lamin A/C gene (LMNA). This spectrum of pathologies, which mostly manifest themselves as dominant traits, includes muscle dystrophies, dilated cardiomyopathies, the premature aging syndrome Hutchinson-Guilford progeria and familial partial lipodystrophy (FPLD). The crystal structure of the lamin A/C mutant R482W, a variant that causes FPLD, has been determined at 1.5 A resolution. A completely novel aggregation state of the C-terminal globular domain and the position of the mutated amino-acid residue suggest means by which the mutation may affect lamin A/C-protein and protein-DNA interactions.

-	~~==Disease==~~	+	Structure of the lamin A/C R482W mutant responsible for dominant familial partial lipodystrophy (FPLD).,Magracheva E, Kozlov S, Stewart CL, Wlodawer A, Zdanov A Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Jul 1;65(Pt, 7):665-70. Epub 2009 Jun 27. PMID:19574635<ref>PMID:19574635</ref>
-	~~[[http://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Defects in LMNA are~~ the ~~cause of Emery-Dreifuss muscular dystrophy type 2, autosomal dominant (EDMD2) [MIM:[http://omim.org/entry/181350 181350]].~~ A degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.<ref>PMID:19933576</ref><ref>PMID:10080180</ref><ref>PMID:10739764</ref><ref>PMID:10939567</ref><ref>PMID:10908904</ref><ref>PMID:11503164</ref><ref>PMID:11792809</ref><ref>PMID:12032588</ref><ref>PMID:14684700</ref><ref>PMID:12649505</ref><ref>PMID:14985400</ref><ref>PMID:15744034</ref><ref>PMID:20848652</ref> Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 3, autosomal recessive (EDMD3) [MIM:[http://omim.org/entry/181350 181350]]. Defects in LMNA are the cause of cardiomyopathy dilated type 1A (CMD1A) [MIM:[http://omim.org/entry/115200 115200]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:18606848</ref><ref>PMID:11792809</ref><ref>PMID:14684700</ref><ref>PMID:10580070</ref><ref>PMID:11561226</ref><ref>PMID:12486434</ref><ref>PMID:11897440</ref><ref>PMID:12628721</ref><ref>PMID:12920062</ref><ref>PMID:15219508</ref><ref>PMID:15140538</ref><ref>PMID:16061563</ref><ref>PMID:21846512</ref> Defects in LMNA are the cause of familial partial lipodystrophy ~~type 2~~ (~~FPLD2~~) ~~[MIM:[http://omim~~.~~org/entry/151660 151660]]; also known as familial partial lipodystrophy Dunnigan type. A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs~~, ~~buttocks~~, ~~trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin~~, ~~fat neck~~, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol.<ref>PMID:11792809</ref><ref>PMID:10739751</ref><ref>PMID:10587585</ref><ref>PMID:10655060</ref><ref>PMID:12015247</ref><ref>PMID:12196663</ref><ref>PMID:12629077</ref><ref>PMID:17250669</ref> Defects in LMNA are the cause of limb-girdle muscular dystrophy type 1B (LGMD1B) [MIM:[http://omim.org/entry/159001 159001]]. LGMD1B is an autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances, dilated cardiomyopathy, and the absence of early contractures. LGMD1B is characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes.<ref>PMID:12032588</ref><ref>PMID:15744034</ref><ref>PMID:10814726</ref><ref>PMID:11525883</ref><ref>PMID:12673789</ref><ref>PMID:17136397</ref> Defects in LMNA are the cause of Charcot-Marie-Tooth disease type 2B1 (CMT2B1) [MIM:[http://omim.org/entry/605588 605588]]. CMT2B1 is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2B1 inheritance is autosomal recessive.<ref>PMID:11799477</ref> Defects in LMNA are the cause of Hutchinson-Gilford progeria syndrome (HGPS) [MIM:[http://omim.org/entry/176670 176670]]. HGPS is a rare genetic disorder characterized by features reminiscent of marked premature aging. Note=HGPS is caused by the toxic accumulation of a mutant form of lamin-A~~/C. This mutant protein~~, called progerin, acts to deregulate mitosis and DNA damage signaling, leading to premature cell death and senescence. Progerin lacks the conserved ZMPSTE24/FACE1 cleavage site and therefore remains permanently farnesylated. Thus, although it can enter the nucleus and associate with the nuclear envelope, it cannot incorporate normally into the nuclear lamina.<ref>PMID:19933576</ref><ref>PMID:12768443</ref><ref>PMID:12927431</ref><ref>PMID:12714972</ref><ref>PMID:15286156</ref><ref>PMID:15622532</ref> Defects in LMNA are the cause of cardiomyopathy dilated with hypergonadotropic hypogonadism (CMDHH) [MIM:[http://omim.org/entry/212112 212112]]. A ~~disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy~~. Patients can present other variable clinical manifestations including mental retardation, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Defects in LMNA are the cause of mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:[http://omim.org/entry/248370 248370]]. A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroide appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased.<ref>PMID:12075506</ref><ref>PMID:15998779</ref><ref>PMID:16278265</ref> Defects in LMNA are a cause of lethal tight skin contracture syndrome (LTSCS) [MIM:[http://omim.org/entry/275210 275210]]; ~~also known as restrictive dermopathy~~ (~~RD). Lethal tight skin contracture syndrome is a rare disorder mainly characterized by intrauterine growth retardation~~, ~~tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia~~), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance.<ref>PMID:~~15317753</ref> Defects in LMNA are the cause of heart~~-~~hand syndrome Slovenian type (HHS-Slovenian) [MIM:[http://omim~~.~~org/entry/610140 610140]]~~. Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations. Defects in LMNA are the cause of muscular dystrophy congenital LMNA-related (MDCL) [MIM:[http://omim.org/entry/613205 613205]]. It is a form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures.<ref>PMID:~~18551513~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http:~~/~~/www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Lamins are components of the nuclear lamina~~, a ~~fibrous layer on the nucleoplasmic side~~ of the ~~inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin~~. ~~Lamin A and C are present in equal amounts in the lamina~~ of ~~mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics~~.<~~ref~~>~~PMID:20079404~~</~~ref~~><ref>PMID:20458013</ref> Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.<ref>PMID:20079404</ref><ref>PMID:20458013</ref>	+	</div>
-		+	== References ==
-	==~~About this Structure==~~	+	<references/>
-	[[3gef]] is a 4 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=3GEF OCA].	+	__TOC__
-		+	</StructureSection>
-	~~==Reference~~==	+	[[Category: Human]]
-	~~<ref group="xtra">PMID:019574635</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	[[Category: Kozlov, S]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Magracheva, E]]
-	[[Category: Kozlov, S.]]	+	[[Category: Stuart, C]]
-	[[Category: Magracheva, E.]]	+	[[Category: Wlodawer, A]]
-	[[Category: Stuart, C.]]	+	[[Category: Zdanov, A]]
-	[[Category: Wlodawer, A.]]	+
-	[[Category: Zdanov, A.]]	+
	[[Category: Cardiomyopathy]]		[[Category: Cardiomyopathy]]
	[[Category: Charcot-marie-tooth disease]]		[[Category: Charcot-marie-tooth disease]]

OCA at 02:07, 25 March 2013

2013-03-25T02:07:37Z

←Older revision		Revision as of 02:07, 25 March 2013
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-	[[Image:3gef.png\|left\|200px]]
-
	{{STRUCTURE_3gef\| PDB=3gef \| SCENE= }}		{{STRUCTURE_3gef\| PDB=3gef \| SCENE= }}
-
	===Crystal structure of the R482W mutant of lamin A/C===		===Crystal structure of the R482W mutant of lamin A/C===
		+	{{ABSTRACT_PUBMED_19574635}}

-	~~{{ABSTRACT_PUBMED_19574635}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 2, autosomal dominant (EDMD2) [MIM:[http://omim.org/entry/181350 181350]]. A degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.<ref>PMID:19933576</ref><ref>PMID:10080180</ref><ref>PMID:10739764</ref><ref>PMID:10939567</ref><ref>PMID:10908904</ref><ref>PMID:11503164</ref><ref>PMID:11792809</ref><ref>PMID:12032588</ref><ref>PMID:14684700</ref><ref>PMID:12649505</ref><ref>PMID:14985400</ref><ref>PMID:15744034</ref><ref>PMID:20848652</ref> Defects in LMNA are the cause of Emery-Dreifuss muscular dystrophy type 3, autosomal recessive (EDMD3) [MIM:[http://omim.org/entry/181350 181350]]. Defects in LMNA are the cause of cardiomyopathy dilated type 1A (CMD1A) [MIM:[http://omim.org/entry/115200 115200]]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.<ref>PMID:18606848</ref><ref>PMID:11792809</ref><ref>PMID:14684700</ref><ref>PMID:10580070</ref><ref>PMID:11561226</ref><ref>PMID:12486434</ref><ref>PMID:11897440</ref><ref>PMID:12628721</ref><ref>PMID:12920062</ref><ref>PMID:15219508</ref><ref>PMID:15140538</ref><ref>PMID:16061563</ref><ref>PMID:21846512</ref> Defects in LMNA are the cause of familial partial lipodystrophy type 2 (FPLD2) [MIM:[http://omim.org/entry/151660 151660]]; also known as familial partial lipodystrophy Dunnigan type. A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol.<ref>PMID:11792809</ref><ref>PMID:10739751</ref><ref>PMID:10587585</ref><ref>PMID:10655060</ref><ref>PMID:12015247</ref><ref>PMID:12196663</ref><ref>PMID:12629077</ref><ref>PMID:17250669</ref> Defects in LMNA are the cause of limb-girdle muscular dystrophy type 1B (LGMD1B) [MIM:[http://omim.org/entry/159001 159001]]. LGMD1B is an autosomal dominant degenerative myopathy with age-related atrioventricular cardiac conduction disturbances, dilated cardiomyopathy, and the absence of early contractures. LGMD1B is characterized by slowly progressive skeletal muscle weakness of the hip and shoulder girdles. Muscle biopsy shows mild dystrophic changes.<ref>PMID:12032588</ref><ref>PMID:15744034</ref><ref>PMID:10814726</ref><ref>PMID:11525883</ref><ref>PMID:12673789</ref><ref>PMID:17136397</ref> Defects in LMNA are the cause of Charcot-Marie-Tooth disease type 2B1 (CMT2B1) [MIM:[http://omim.org/entry/605588 605588]]. CMT2B1 is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. CMT2B1 inheritance is autosomal recessive.<ref>PMID:11799477</ref> Defects in LMNA are the cause of Hutchinson-Gilford progeria syndrome (HGPS) [MIM:[http://omim.org/entry/176670 176670]]. HGPS is a rare genetic disorder characterized by features reminiscent of marked premature aging. Note=HGPS is caused by the toxic accumulation of a mutant form of lamin-A/C. This mutant protein, called progerin, acts to deregulate mitosis and DNA damage signaling, leading to premature cell death and senescence. Progerin lacks the conserved ZMPSTE24/FACE1 cleavage site and therefore remains permanently farnesylated. Thus, although it can enter the nucleus and associate with the nuclear envelope, it cannot incorporate normally into the nuclear lamina.<ref>PMID:19933576</ref><ref>PMID:12768443</ref><ref>PMID:12927431</ref><ref>PMID:12714972</ref><ref>PMID:15286156</ref><ref>PMID:15622532</ref> Defects in LMNA are the cause of cardiomyopathy dilated with hypergonadotropic hypogonadism (CMDHH) [MIM:[http://omim.org/entry/212112 212112]]. A disorder characterized by the association of genital anomalies, hypergonadotropic hypogonadism and dilated cardiomyopathy. Patients can present other variable clinical manifestations including mental retardation, skeletal anomalies, scleroderma-like skin, graying and thinning of hair, osteoporosis. Dilated cardiomyopathy is characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Defects in LMNA are the cause of mandibuloacral dysplasia with type A lipodystrophy (MADA) [MIM:[http://omim.org/entry/248370 248370]]. A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, progeroide appearance, partial alopecia, soft tissue calcinosis, joint contractures, and partial lipodystrophy with loss of subcutaneous fat from the extremities. Adipose tissue in the face, neck and trunk is normal or increased.<ref>PMID:12075506</ref><ref>PMID:15998779</ref><ref>PMID:16278265</ref> Defects in LMNA are a cause of lethal tight skin contracture syndrome (LTSCS) [MIM:[http://omim.org/entry/275210 275210]]; also known as restrictive dermopathy (RD). Lethal tight skin contracture syndrome is a rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance.<ref>PMID:15317753</ref> Defects in LMNA are the cause of heart-hand syndrome Slovenian type (HHS-Slovenian) [MIM:[http://omim.org/entry/610140 610140]]. Heart-hand syndrome (HHS) is a clinically and genetically heterogeneous disorder characterized by the co-occurrence of a congenital cardiac disease and limb malformations. Defects in LMNA are the cause of muscular dystrophy congenital LMNA-related (MDCL) [MIM:[http://omim.org/entry/613205 613205]]. It is a form of congenital muscular dystrophy. Patients present at birth, or within the first few months of life, with hypotonia, muscle weakness and often with joint contractures.<ref>PMID:18551513</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/LMNA_HUMAN LMNA_HUMAN]] Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin. Lamin A and C are present in equal amounts in the lamina of mammals. Plays an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics.<ref>PMID:20079404</ref><ref>PMID:20458013</ref> Prelamin-A/C can accelerate smooth muscle cell senescence. It acts to disrupt mitosis and induce DNA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence.<ref>PMID:20079404</ref><ref>PMID:20458013</ref>

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

	==Reference==		==Reference==
-	<ref group="xtra">PMID:019574635</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019574635</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Kozlov, S.]]		[[Category: Kozlov, S.]]

OCA: Protected "3gef" [edit=sysop:move=sysop]

2013-02-20T14:26:34Z

Protected "3gef" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:26, 20 February 2013

OCA at 14:26, 20 February 2013

2013-02-20T14:26:29Z

←Older revision		Revision as of 14:26, 20 February 2013
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-	~~{{Seed}}~~	+	[[Image:3gef.png\|left\|200px]]
-	[[Image:3gef.~~jpg~~\|left\|200px]]	+

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3gef", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3gef\| PDB=3gef \| SCENE= }}		{{STRUCTURE_3gef\| PDB=3gef \| SCENE= }}

	===Crystal structure of the R482W mutant of lamin A/C===		===Crystal structure of the R482W mutant of lamin A/C===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19574635}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19574635 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19574635}}		{{ABSTRACT_PUBMED_19574635}}

	==About this Structure==		==About this Structure==
-	~~3GEF~~ is a 4 ~~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=3GEF OCA].	+	[[3gef]] is a 4 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=3GEF OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19574635~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019574635</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Kozlov, S.]]		[[Category: Kozlov, S.]]
Line 30:		Line 18:
	[[Category: Wlodawer, A.]]		[[Category: Wlodawer, A.]]
	[[Category: Zdanov, A.]]		[[Category: Zdanov, A.]]
-	[[Category: Acetylation]]
-	[[Category: Alternative splicing]]
	[[Category: Cardiomyopathy]]		[[Category: Cardiomyopathy]]
	[[Category: Charcot-marie-tooth disease]]		[[Category: Charcot-marie-tooth disease]]
-	[[Category: Coiled coil]]
	[[Category: Disease mutation]]		[[Category: Disease mutation]]
	[[Category: Immunoglobulin fold]]		[[Category: Immunoglobulin fold]]
Line 45:		Line 30:
	[[Category: Prenylation]]		[[Category: Prenylation]]
	[[Category: Structural protein]]		[[Category: Structural protein]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 5 10:24:07 2009''

OCA at 07:24, 5 August 2009

2009-08-05T07:24:13Z

←Older revision		Revision as of 07:24, 5 August 2009
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3gef.jpg\|left\|200px]]

-	The ~~entry 3gef~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3gef", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3gef\| PDB=3gef \| SCENE= }}

-	~~Authors: Magracheva, E., Kozlov, S., Stuart,~~ C~~., Wlodawer, A., Zdanov, A.~~	+	===Crystal structure of the R482W mutant of lamin A/C===

-	Description: Crystal structure of the R482W mutant of lamin A/C

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun Mar 22~~ 10:24:27 2009''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_19574635}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 19574635 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_19574635}}
		+
		+	==About this Structure==
		+	3GEF is a 4 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=3GEF OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:19574635</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Kozlov, S.]]
		+	[[Category: Magracheva, E.]]
		+	[[Category: Stuart, C.]]
		+	[[Category: Wlodawer, A.]]
		+	[[Category: Zdanov, A.]]
		+	[[Category: Acetylation]]
		+	[[Category: Alternative splicing]]
		+	[[Category: Cardiomyopathy]]
		+	[[Category: Charcot-marie-tooth disease]]
		+	[[Category: Coiled coil]]
		+	[[Category: Disease mutation]]
		+	[[Category: Immunoglobulin fold]]
		+	[[Category: Intermediate filament]]
		+	[[Category: Lamin]]
		+	[[Category: Limb-girdle muscular dystrophy]]
		+	[[Category: Lipoprotein]]
		+	[[Category: Nucleus]]
		+	[[Category: Phosphoprotein]]
		+	[[Category: Prenylation]]
		+	[[Category: Structural protein]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 5 10:24:07 2009''

OCA at 08:24, 22 March 2009

2009-03-22T08:24:27Z

←Older revision		Revision as of 08:24, 22 March 2009
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3gef is ON HOLD	+	The entry 3gef is ON HOLD until Paper Publication

-	Authors: Magracheva E., Kozlov S., Stuart C., Wlodawer A., Zdanov A.	+	Authors: Magracheva, E., Kozlov, S., Stuart, C., Wlodawer, A., Zdanov, A.

	Description: Crystal structure of the R482W mutant of lamin A/C		Description: Crystal structure of the R482W mutant of lamin A/C

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed~~ Mar ~~11 11~~:11:34 2009''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 22 10:24:27 2009''