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2kav

From Proteopedia

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Revision as of 10:35, 18 July 2018

Solution structure of the human Voltage-gated Sodium Channel, brain isoform (Nav1.2)

Structural highlights

2kav is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1qg9, 1byy
Gene:	NAC2, SCN2A, SCN2A1, SCN2A2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SCN2A_HUMAN] Defects in SCN2A are the cause of seizures, benign familial infantile type 3 (BFIS3) [MIM:607745]. An autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae.^[1] ^[2] ^[3] ^[4] Defects in SCN2A are the cause of epileptic encephalopathy early infantile type 11 (EIEE11) [MIM:613721]. EIEE11 is an autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities.^[5] ^[6]

Function

[SCN2A_HUMAN] Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.

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

Voltage-gated sodium channels initiate the rapid upstroke of action potentials in many excitable tissues. Mutations within intracellular C-terminal sequences of specific channels underlie a diverse set of channelopathies, including cardiac arrhythmias and epilepsy syndromes. The three-dimensional structure of the C-terminal residues 1777-1882 of the human NaV1.2 voltage-gated sodium channel has been determined in solution by NMR spectroscopy at pH 7.4 and 290.5 K. The ordered structure extends from residues Leu-1790 to Glu-1868 and is composed of four alpha-helices separated by two short anti-parallel beta-strands; a less well defined helical region extends from residue Ser-1869 to Arg-1882, and a disordered N-terminal region encompasses residues 1777-1789. Although the structure has the overall architecture of a paired EF-hand domain, the NaV1.2 C-terminal domain does not bind Ca2+ through the canonical EF-hand loops, as evidenced by monitoring 1H,15N chemical shifts during aCa2+ titration. Backbone chemical shift resonance assignments and Ca2+ titration also were performed for the NaV1.5 (1773-1878) isoform, demonstrating similar secondary structure architecture and the absence of Ca2+ binding by the EF-hand loops. Clinically significant mutations identified in the C-terminal region of NaV1 sodium channels cluster in the helix I-IV interface and the helix II-III interhelical segment or in helices III and IV of the NaV1.2 (1777-1882) structure.

Solution structure of the NaV1.2 C-terminal EF-hand domain.,Miloushev VZ, Levine JA, Arbing MA, Hunt JF, Pitt GS, Palmer AG 3rd J Biol Chem. 2009 Mar 6;284(10):6446-54. Epub 2009 Jan 7. PMID:19129176^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sugawara T, Tsurubuchi Y, Agarwala KL, Ito M, Fukuma G, Mazaki-Miyazaki E, Nagafuji H, Noda M, Imoto K, Wada K, Mitsudome A, Kaneko S, Montal M, Nagata K, Hirose S, Yamakawa K. A missense mutation of the Na+ channel alpha II subunit gene Na(v)1.2 in a patient with febrile and afebrile seizures causes channel dysfunction. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6384-9. PMID:11371648 doi:10.1073/pnas.111065098
↑ Heron SE, Crossland KM, Andermann E, Phillips HA, Hall AJ, Bleasel A, Shevell M, Mercho S, Seni MH, Guiot MC, Mulley JC, Berkovic SF, Scheffer IE. Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet. 2002 Sep 14;360(9336):851-2. PMID:12243921 doi:10.1016/S0140-6736(02)09968-3
↑ Berkovic SF, Heron SE, Giordano L, Marini C, Guerrini R, Kaplan RE, Gambardella A, Steinlein OK, Grinton BE, Dean JT, Bordo L, Hodgson BL, Yamamoto T, Mulley JC, Zara F, Scheffer IE. Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy. Ann Neurol. 2004 Apr;55(4):550-7. PMID:15048894 doi:10.1002/ana.20029
↑ Liao Y, Deprez L, Maljevic S, Pitsch J, Claes L, Hristova D, Jordanova A, Ala-Mello S, Bellan-Koch A, Blazevic D, Schubert S, Thomas EA, Petrou S, Becker AJ, De Jonghe P, Lerche H. Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy. Brain. 2010 May;133(Pt 5):1403-14. doi: 10.1093/brain/awq057. Epub 2010 Apr 5. PMID:20371507 doi:10.1093/brain/awq057
↑ Ogiwara I, Ito K, Sawaishi Y, Osaka H, Mazaki E, Inoue I, Montal M, Hashikawa T, Shike T, Fujiwara T, Inoue Y, Kaneda M, Yamakawa K. De novo mutations of voltage-gated sodium channel alphaII gene SCN2A in intractable epilepsies. Neurology. 2009 Sep 29;73(13):1046-53. doi: 10.1212/WNL.0b013e3181b9cebc. PMID:19786696 doi:10.1212/WNL.0b013e3181b9cebc
↑ Liao Y, Anttonen AK, Liukkonen E, Gaily E, Maljevic S, Schubert S, Bellan-Koch A, Petrou S, Ahonen VE, Lerche H, Lehesjoki AE. SCN2A mutation associated with neonatal epilepsy, late-onset episodic ataxia, myoclonus, and pain. Neurology. 2010 Oct 19;75(16):1454-8. doi: 10.1212/WNL.0b013e3181f8812e. PMID:20956790 doi:10.1212/WNL.0b013e3181f8812e
↑ Miloushev VZ, Levine JA, Arbing MA, Hunt JF, Pitt GS, Palmer AG 3rd. Solution structure of the NaV1.2 C-terminal EF-hand domain. J Biol Chem. 2009 Mar 6;284(10):6446-54. Epub 2009 Jan 7. PMID:19129176 doi:10.1074/jbc.M807401200

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2kav"

@@ Line 1: / Line 1: @@
 ==Solution structure of the human Voltage-gated Sodium Channel, brain isoform (Nav1.2)==
 <StructureSection load='2kav' size='340' side='right' caption='[[2kav]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1qg9|1qg9]], [[1byy|1byy]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NAC2, SCN2A, SCN2A1, SCN2A2 ([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=2kav FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kav OCA], [http://pdbe.org/2kav PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kav RCSB], [http://www.ebi.ac.uk/pdbsum/2kav 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=2kav FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kav OCA], [http://pdbe.org/2kav PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kav RCSB], [http://www.ebi.ac.uk/pdbsum/2kav PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kav ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ka/2kav_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ka/2kav_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 44: / Line 45: @@
 [[Category: Palmer, A G]]
 [[Category: Pitt, G S]]
+[[Category: Alternative splicing]]
 [[Category: Disease mutation]]
 [[Category: Epilepsy]]
@@ Line 50: / Line 52: @@
 [[Category: Ionic channel]]
 [[Category: Membrane]]
+[[Category: Polymorphism]]
+[[Category: Sodium]]
 [[Category: Sodium channel]]
 [[Category: Sodium transport]]
@@ Line 56: / Line 60: @@
 [[Category: Transport protein]]
 [[Category: Transport protein regulator]]
+[[Category: Ubl conjugation]]
 [[Category: Voltage-gated channel]]
 [[Category: Voltage-gated sodium channel]]

2kav

From Proteopedia

Revision as of 10:35, 18 July 2018

Solution structure of the human Voltage-gated Sodium Channel, brain isoform (Nav1.2)

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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