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| | ==Solution Structure of the Human Beta4a-A Domain== | | ==Solution Structure of the Human Beta4a-A Domain== |
| - | <StructureSection load='2d46' size='340' side='right' caption='[[2d46]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='2d46' size='340' side='right'caption='[[2d46]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2d46]] 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=2D46 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2D46 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2d46]] 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=2D46 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2D46 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CACNB4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2d46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d46 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2d46 RCSB], [http://www.ebi.ac.uk/pdbsum/2d46 PDBsum]</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=2d46 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2d46 OCA], [https://pdbe.org/2d46 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2d46 RCSB], [https://www.ebi.ac.uk/pdbsum/2d46 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2d46 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/CACB4_HUMAN CACB4_HUMAN]] Defects in CACNB4 are the cause of susceptibility to epilepsy, idiopathic generalized type 9 (EIG9) [MIM:[http://omim.org/entry/607682 607682]]. A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain.<ref>PMID:10762541</ref> Defects in CACNB4 are the cause of susceptibility to juvenile myoclonic epilepsy type 6 (EJM6) [MIM:[http://omim.org/entry/607682 607682]]. EJM6 is a subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. Defects in CACNB4 are the cause of episodic ataxia type 5 (EA5) [MIM:[http://omim.org/entry/613855 613855]]. EA5 is a disorder characterized by episodes of vertigo and ataxia that last for several hours. Interictal examination show spontaneous downbeat and gaze-evoked nystagmus, mild dysarthria and truncal ataxia.<ref>PMID:10762541</ref> | + | [https://www.uniprot.org/uniprot/CACB4_HUMAN CACB4_HUMAN] Defects in CACNB4 are the cause of susceptibility to epilepsy, idiopathic generalized type 9 (EIG9) [MIM:[https://omim.org/entry/607682 607682]. A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain.<ref>PMID:10762541</ref> Defects in CACNB4 are the cause of susceptibility to juvenile myoclonic epilepsy type 6 (EJM6) [MIM:[https://omim.org/entry/607682 607682]. EJM6 is a subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. Defects in CACNB4 are the cause of episodic ataxia type 5 (EA5) [MIM:[https://omim.org/entry/613855 613855]. EA5 is a disorder characterized by episodes of vertigo and ataxia that last for several hours. Interictal examination show spontaneous downbeat and gaze-evoked nystagmus, mild dysarthria and truncal ataxia.<ref>PMID:10762541</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CACB4_HUMAN CACB4_HUMAN]] The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting. | + | [https://www.uniprot.org/uniprot/CACB4_HUMAN CACB4_HUMAN] The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d4/2d46_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/d4/2d46_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> |
| | </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=2d46 ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | 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 2d46" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ion channels|Ion channels]] | + | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Horne, W A]] | + | [[Category: Large Structures]] |
| - | [[Category: Lyons, B A]] | + | [[Category: Horne WA]] |
| - | [[Category: Rithner, C D]] | + | [[Category: Lyons BA]] |
| - | [[Category: Vendel, A C]] | + | [[Category: Rithner CD]] |
| - | [[Category: Alternative spliving]] | + | [[Category: Vendel AC]] |
| - | [[Category: Beta4a subunit]]
| + | |
| - | [[Category: Ca2+ channel]]
| + | |
| - | [[Category: Membrane-associated guanylate-kinase]]
| + | |
| - | [[Category: Metal transport]]
| + | |
| - | [[Category: Protein structure]]
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| Structural highlights
Disease
CACB4_HUMAN Defects in CACNB4 are the cause of susceptibility to epilepsy, idiopathic generalized type 9 (EIG9) [MIM:607682. A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain.[1] Defects in CACNB4 are the cause of susceptibility to juvenile myoclonic epilepsy type 6 (EJM6) [MIM:607682. EJM6 is a subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. Defects in CACNB4 are the cause of episodic ataxia type 5 (EA5) [MIM:613855. EA5 is a disorder characterized by episodes of vertigo and ataxia that last for several hours. Interictal examination show spontaneous downbeat and gaze-evoked nystagmus, mild dysarthria and truncal ataxia.[2]
Function
CACB4_HUMAN The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ca2+ channel beta subunits regulate trafficking and gating (opening and closing) of voltage-dependent Ca2+ channel alpha1 subunits. Based on primary sequence comparisons, they are thought to be modular structures composed of five domains (A-E) that are related to the large family of membrane associated guanylate-kinase (MAGUK) proteins. The crystal structures of the beta subunit core, B-D, domains have recently been reported; however, very little is known about the structures of the A and E domains. The N-terminal A domain is a hypervariable region that differs among the four subtypes of Ca2+ channel beta subunits (beta1-beta4). Furthermore, this domain undergoes alternative splicing to create multiple N-terminal structures within a given gene class that have distinct effects on gating. We have solved the solution structure of the A domain of the human beta4a subunit, a splice variant that we have shown previously to have alpha1 subunit subtype-specific effects on Ca2+ channel trafficking and gating.
Solution structure of the N-terminal A domain of the human voltage-gated Ca2+channel beta4a subunit.,Vendel AC, Rithner CD, Lyons BA, Horne WA Protein Sci. 2006 Feb;15(2):378-83. Epub 2005 Dec 29. PMID:16385006[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Escayg A, De Waard M, Lee DD, Bichet D, Wolf P, Mayer T, Johnston J, Baloh R, Sander T, Meisler MH. Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet. 2000 May;66(5):1531-9. Epub 2000 Apr 4. PMID:10762541 doi:S0002-9297(07)62983-8
- ↑ Escayg A, De Waard M, Lee DD, Bichet D, Wolf P, Mayer T, Johnston J, Baloh R, Sander T, Meisler MH. Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet. 2000 May;66(5):1531-9. Epub 2000 Apr 4. PMID:10762541 doi:S0002-9297(07)62983-8
- ↑ Vendel AC, Rithner CD, Lyons BA, Horne WA. Solution structure of the N-terminal A domain of the human voltage-gated Ca2+channel beta4a subunit. Protein Sci. 2006 Feb;15(2):378-83. Epub 2005 Dec 29. PMID:16385006 doi:10.1110/ps.051894506
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