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KCNA1  -  potassium channel, voltage gated shaker...

Homo sapiens

Synonyms: AEMK, EA1, HBK1, HUK1, KV1.1, ...
 
 
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Disease relevance of KCNA1

  • Episodic ataxia type 1 (EA-1) is caused by missense mutations in the potassium channel gene KCNA1, whereas episodic ataxia type 2 (EA-2) is caused by missense and nonsense mutations in the calcium channel gene CACNA1A [1].
  • A long-range restriction map of an 800-kb region was constructed and used to refine the mesothelioma breakpoint to a region of approximately 100 kb, flanked by the potassium channel genes KCNA1 and KCNA5 [2].
  • Mutation analysis of the KCNA1 coding region in these families identified four different missense point mutations present in the heterozygous state, indicating that EA/myokymia can result from mutations in this gene [3].
  • We conclude that mutations in the potassium channel gene (KCNA1) can cause severe neuromyotonia resulting in marked skeletal deformities even if episodic ataxia is not prominent [4].
  • Vaccine trials with partially purified EA1 demonstrated that it neither elicits protective antibody against anthrax nor delays time to death in guinea pigs challenged intramuscularly with virulent Ames strain spores [5].
 

High impact information on KCNA1

  • In support of this suggestion, we have found HBK1 to be expressed in the apical meristem in the central population of nondifferentiated stem cells, but not in organ primordia developing at the flanks of the meristem [6].
  • We recently isolated a family of three closely related mouse K+ channel genes (MK1, MK2, and MK3) with coding regions contained in single uninterrupted exons [7].
  • Dinucleotide repeat polymorphisms near the KCNA6 and KCNA1 loci [8].
  • Heterologous expression of the proteins encoded by the mutant KCNA1 genes suggest that the four point mutations impair delayed-rectifier type potassium currents by different mechanisms [9].
  • Point mutations in the voltage-gated potassium channel gene KCNA1 on chromosome 12p associate with EA1 [9].
 

Chemical compound and disease context of KCNA1

 

Biological context of KCNA1

 

Anatomical context of KCNA1

  • The transverse area of the large abdominal arteries (abdominal aorta, common iliac arteries) was significantly greater in EA2 than in both EA1 and CO and partly greater in EA1 than in CO [14].
  • BMD was measured in the lumbar spine, the femoral neck, and the proximal tibia by dual energy absorptiometry (DEXA, Nordland XR 26 MK1) [15].
 

Associations of KCNA1 with chemical compounds

  • The mutation c.1025G>T replaces a highly conserved serine with isoleucine at position 342 (p.Ser342Ile) in the highly conserved fifth transmembrane domain of the KCNA1 [16].
  • Replacement of this residue by tyrosine, the amino acid found in the equivalent position of the homologous but non-inactivating channel RBK1, reduced inactivation of RGK5 over a 5 s depolarizing pulse from 84.3 +/- 1.9% to 18.3 +/- 1.1% [17].
  • The MK-1 antigen, also termed as Ep-CAM, is a membrane glycoprotein that is overexpressed on the majority of tumor cells of epithelial origin and thereby can be used as a target of immunodetection and immunotherapy of cancer [18].
  • Three sets of monoclonal antibodies against bradykinin (MBK1, MBK2, MBK3) were generated by somatic cell fusion, characterized by their peptide specificity and compared to the known ligand specificity of the kinin receptor subtypes [19].
 

Other interactions of KCNA1

  • Molecular biological characterization of the YAC-insert DNAs revealed that three KCNA genes--KCNA1, KCNA5, KCNA6--are clustered within approximately 300 kb of insert-DNA derived from chromosome 12p13 [12].
  • Northern blot analyses of the KCNA1, KCNA5 and KCNA6 mRNAs in different human brain areas show that the genes are distinctly expressed [12].
  • EA-1 is due to different heterozygous missense point mutations in a voltage-gated (delayed rectifier) potassium channel gene (KCNA1/Kv1.1) on chromosome 12p13, whereas EA-2 is caused by mutations of the cerebral P/Q-type calcium channel alpha 1 subunit gene CACNL1A4 localized on chromosome 19p, which is highly expressed in the cerebellum [20].
  • Sequence scanning of overlapping cosmids has identified three additional genes, TMPO, LDHB and KCNA1, which map to human chromosome 12, with the latter two mapping to 12p12-11 [21].
  • However, mutations of KCNA1, encoding the K(+) channel subunit hKv1.1, have been reported in rare families with neuromyotonia, and mutations in KCNQ2, encoding voltage-gated potassium M channel subunit, in families with benign neonatal seizures and myokymia [22].
 

Analytical, diagnostic and therapeutic context of KCNA1

  • By direct sequence analysis, a different missense mutation of the potassium channel gene (KCNA1) has been identified in three families with EA [23].
  • However, by linkage mapping, sequencing and polymorphism analysis, all affecteds were found to have a novel mutation in KCNA1 [16].
  • Following vaccination with the live spore vaccine, the EA1 protein was the predominant antigen recognized, as determined by electrophoretic immunotransblots [5].
  • To address the question of whether MK-1, the same type-I membrane protein, is also released into the sera, we developed a sandwich-type enzyme-linked immunosorbent assay (ELISA) system by preparing a recombinant MK-1 protein and two anti-MK-1 monoclonal antibodies with different epitope specificities [18].
  • The approximate molecular weights of HUK-1, -2 and -3 were estimated to be 2.7 X 10(4), 2.7 X 10(4), and 2.9 X 10(4), respectively, by gel filtration on a Sephadex G-100 column [24].

References

  1. Genetics of familial episodic vertigo and ataxia. Baloh, R.W., Jen, J.C. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
  2. A physical map of the region spanning the chromosome 12 translocation breakpoint in a mesothelioma with a t(X;12)(q22;p13). Aerssens, J., Guo, C., Vermeesch, J., Baens, M., Browne, D., Litt, M., Van Den Berghe, H., Marynen, P. Cytogenet. Cell Genet. (1995) [Pubmed]
  3. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Browne, D.L., Gancher, S.T., Nutt, J.G., Brunt, E.R., Smith, E.A., Kramer, P., Litt, M. Nat. Genet. (1994) [Pubmed]
  4. Expanding the phenotype of potassium channelopathy: severe neuromyotonia and skeletal deformities without prominent Episodic Ataxia. Kinali, M., Jungbluth, H., Eunson, L.H., Sewry, C.A., Manzur, A.Y., Mercuri, E., Hanna, M.G., Muntoni, F. Neuromuscul. Disord. (2004) [Pubmed]
  5. Immunological analysis of cell-associated antigens of Bacillus anthracis. Ezzell, J.W., Abshire, T.G. Infect. Immun. (1988) [Pubmed]
  6. A homeobox gene with potential developmental control function in the meristem of the conifer Picea abies. Sundås-Larsson, A., Svenson, M., Liao, H., Engström, P. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  7. Expression and chromosomal localization of a lymphocyte K+ channel gene. Grissmer, S., Dethlefs, B., Wasmuth, J.J., Goldin, A.L., Gutman, G.A., Cahalan, M.D., Chandy, K.G. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  8. Dinucleotide repeat polymorphisms near the KCNA6 and KCNA1 loci. Browne, D.L., Litt, M. Hum. Mol. Genet. (1994) [Pubmed]
  9. Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability. Eunson, L.H., Rea, R., Zuberi, S.M., Youroukos, S., Panayiotopoulos, C.P., Liguori, R., Avoni, P., McWilliam, R.C., Stephenson, J.B., Hanna, M.G., Kullmann, D.M., Spauschus, A. Ann. Neurol. (2000) [Pubmed]
  10. Molecular cloning and cultivar specific expression of MAP kinases from Capsicum annuum. Shin, H.J., Lee, D.E., Shin, D.H., Kim, K.U., Kim, H.Y., Ohashi, Y., Han, O., Baik, M.G., Back, K. Mol. Cells (2001) [Pubmed]
  11. Molecular cloning, characterization, and genomic localization of a human potassium channel gene. Curran, M.E., Landes, G.M., Keating, M.T. Genomics (1992) [Pubmed]
  12. Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13. Albrecht, B., Weber, K., Pongs, O. Recept. Channels (1995) [Pubmed]
  13. Variable K(+) channel subunit dysfunction in inherited mutations of KCNA1. Rea, R., Spauschus, A., Eunson, L.H., Hanna, M.G., Kullmann, D.M. J. Physiol. (Lond.) (2002) [Pubmed]
  14. Ultrasound of the abdomen in endurance athletes. Gabriel, H., Kindermann, W. European journal of applied physiology and occupational physiology. (1996) [Pubmed]
  15. Increased bone mineral density after prolonged electrically induced cycle training of paralyzed limbs in spinal cord injured man. Mohr, T., Podenphant, J., Biering-Sorensen, F., Galbo, H., Thamsborg, G., Kjaer, M. Calcif. Tissue Int. (1997) [Pubmed]
  16. A novel mutation in KCNA1 causes episodic ataxia without myokymia. Lee, H., Wang, H., Jen, J.C., Sabatti, C., Baloh, R.W., Nelson, S.F. Hum. Mutat. (2004) [Pubmed]
  17. Current inactivation involves a histidine residue in the pore of the rat lymphocyte potassium channel RGK5. Busch, A.E., Hurst, R.S., North, R.A., Adelman, J.P., Kavanaugh, M.P. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  18. Preparation of recombinant MK-1/Ep-CAM and establishment of an ELISA system for determining soluble MK-1/Ep-CAM levels in sera of cancer patients. Abe, H., Kuroki, M., Imakiire, T., Yamauchi, Y., Yamada, H., Arakawa, F., Kuroki, M. J. Immunol. Methods (2002) [Pubmed]
  19. Anti-idiotypic antibodies against the kinin receptor. Haasemann, M., Buschko, J., Faussner, A., Roscher, A.A., Hoebeke, J., Burch, R., Muller-Esterl, W. Agents Actions Suppl. (1992) [Pubmed]
  20. Episodic ataxia type 1 and 2 (familial periodic ataxia/vertigo). Brandt, T., Strupp, M. Audiol. Neurootol. (1997) [Pubmed]
  21. Genomic structure and expression of parathyroid hormone-related protein gene (PTHrP) in a teleost, Fugu rubripes. Power, D.M., Ingleton, P.M., Flanagan, J., Canario, A.V., Danks, J., Elgar, G., Clark, M.S. Gene (2000) [Pubmed]
  22. Inherited neuromyotonia: A clinical and genetic study of a family. Falace, A., Striano, P., Manganelli, F., Coppola, A., Striano, S., Minetti, C., Zara, F. Neuromuscul. Disord. (2007) [Pubmed]
  23. Three novel KCNA1 mutations in episodic ataxia type I families. Scheffer, H., Brunt, E.R., Mol, G.J., van der Vlies, P., Stulp, R.P., Verlind, E., Mantel, G., Averyanov, Y.N., Hofstra, R.M., Buys, C.H. Hum. Genet. (1998) [Pubmed]
  24. Studies on urinary kallikreins. I. Purification and characterization of human urinary kallikreins. Matsuda, Y., Miyazaki, K., Moriya, H., Fujimoto, Y., Hojima, Y., Moriwaki, C. J. Biochem. (1976) [Pubmed]
 
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