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Citation: Viroj W (2008) Possible Single Nucleotide Polymorphism (SNP) in the Nucleic Sequence of
A-kinase-anchoring Protein 9. J Proteomics Bioinform 1: 227-229.
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Copyright: © 2008 Viroj W. This is an open-access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and
source are credited.
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Abstract
In cardiac physiology, ion channel macromolecular complexes can be formed by the strong correlation of Akinase
anchoring proteins, therefore, AKAP becomes an important antiarrhytmic target. Here, the author performed
a bioinformatics analysis to study the possible single nucleotide polymorphism (SNP) in the amino acid
sequence of AKAP9. In this work, the author could not identify any SNP with in AKAP9. This confirms that there
is no report on SNP on this molecule.
Key words
A-kinase anchoring protein; arrhythmia; single nucleotide polymorphism
Introduction
In normal cardiac physiology, sympathetic nervous system
(SNS) regulation of cardiac action potential duration
(APD), mediated by beta-adrenergic receptor (betaAR)
activation, usually requires assembly of A-kinase anchoring
protein (AKAP)9 (Yotiao) with the I(Ks) potassium channel
alpha subunit (KCNQ1) (Chen et al., 2001). Ion channel
macromolecular complexes can be formed by the strong
correlation of AKAPs (Chen et al, 2006, Marx and
Kurokawa, 2006). Therefore, AKAP becomes an important
antiarrhytmic target (Marx and Kurokawa, 2006). Analysis
on the AKAP in depth helps better understand the pathogenesis
of this protein-relate arrythmic disorder. AKAP disorder
can be seen in the recent reports (Lin et al., 1998, Tao
et al., 2006), however, the prevalence of mutations in the
AKAP is not well known. In addition, single nucleotide polymorphism
(SNP) within AKAP has never been mentioned.
Importance of SNP study for AKAP and other AKAP
targets for new therapeutic interventions should be mentioned. Burns-Hamuro et al said that there had been considerable
progress in understanding the structural features
of this AKAP and its interaction with protein kinase A
(Burns-Hamuro et al., 2004). Burns-Hamuro et al reported
that comprehensive analysis of the PKA binding motif could
lead to the development of novel peptides derived from DAKAP2
and could be useful tools in probing the function of
this AKAP in cellular and animal models (Burns-Hamuro et al., 2004). However, there is limited reported on AKAP9.
There was a paper by Rudd et al describing the possible
correlation of SNP for AKAP9 and lung cancer (Rudd et
al., 2006). However, there was no proof from this work
(Rudd et al., 2006). Here, the author performed a
bioinformatics analysis to study the SNP in the amino acid
sequence of AKAP9.
Materials and Methods
At first, the database Expert Protein Analysis System
(ExPASY) (Gasteiger et al., 2003) was used for searching
for the amino acid sequence of AKAP9. Then the derived
sequences were used for further study for SNP. GENSNiP
was further used for identification on SNP within the
derived sequence. Briefly, GEN-SNiP help finds polymorphisms
present in DNA sequences with respect to a standard
reference sequence. This tool is selected because it is
only one simple online assess tool and is confirmed for its
validity. The output lists substitutions, insertions and deletions.
Since there is no other similar tool to GEN-SNiP, further
comparative study to other tool cannot be performed.
Result
In this work, AKAP9 (NG_007968) was used for
further study. There is no identified SNP for this sequence.
Discussion
Importance of SNP search for target drug discovery/
new therapeutic interventions should be mentioned in the
present post-genomics era. The analysis of SNPs permits
determining relationships between genotypic and phenotypic
information as well as the identification of SNPs related to
a disease, which can be useful for further drug development
(Shah and Kusiak, 2004). The good examples are on
antineoplastic (Mack et al., 2008) and cardiovascular drugs
(Borgiani et al., 2007). There are numerous experimental
and clinical data supporting the existence or variant AKAP
proteins (Chen et al., 2001). However, the exact functions
of variant AKAP proteins, either physiological or pathological,
are still unclear, although roles for some AKAP variants
in cardiac arrythmia progression might be consistent
with the accumulated data (Chen et al., 2001; Saucerman
et al., 2004). On one hand, AKAP polymorphism might connect
with some rare syndromes of arrhythmic disorder and
on other side it is the post-receptor modifications that very
well explain the molecular pathogenesis of AKAP and arrythmia.
Identification of the SNP within AKAP can be useful
for further researches to understand the pathogenesis of
AKAP disorder. In this work, the author could not identify
any SNP with in AKAP9. This confirms that there is no
report on SNP on this molecule although there is for other
AKAPs
(Burns-Hamuro et al., 2004; Frank et al., 2004).
Conclusions & Future Perspectives
In this work, the author used a novel bioinformatics tool
to find possible SNP in the amino acid sequence of AKAP9
and found no SNP. This might imply that the AKAP9 might
have no polymorphism. However, due to the limitation of
the present tool, the conclusion cannot be reached. Future
analysis by future available tool is suggested. In addition, a
study on the probable mutated prone position, weak linkage
analysis, is another in silico methods suitable for this AKAP
protein.
Declaration on Conflict of Interest
The author hereby would like to declare for no confliction
of interest in this work.
References
-
Borgiani P, Ciccacci C, Forte V, Romano S, Federici G,
Novelli G (2007) Allelic variants in the CYP2C9 and VKORC1 loci and interindividual variability in the anticoagulant dose effect of warfarin in Italians.
Pharmacogenomics 8: 1545-50. [ FIND THIS ARTICLE ONLINE ]
-
Burns HLL, Barraclough DM, Taylor SS (2004) Identification and functional analysis of dual-specific A kinase-
anchoring protein-2 Methods Enzymol 390: 354-74.
-
Chen L, Marquardt ML, Tester DJ, Sampson KJ,
Ackerman MJ, Kass RS (2007) Mutation of an A-kinaseanchoring protein causes long-QT syndrome. Proc Natl Acad Sci USA 104: 20990-5. [ FIND THIS ARTICLE ONLINE ]
-
Chen L, Kass RS (2006) Dual roles of the A kinaseanchoring
protein Yotiao in the modulation of a cardiac potassium channel: a passive adaptor versus an active regulator. Eur J Cell Biol 85: 623-6. [ FIND THIS ARTICLE ONLINE ]
-
Frank B, Wiestler M, Kropp S, Hemminki K, Spurdle
AB, Sutter C, Wappenschmidt B, Chen X, Beesley J, Hopper
JL; Australian Breast Cancer Family Study Investigators,,
Meindl A, Kiechle M, Slanger T, Bugert P, Schmutzler
RK, Bartram CR, Flesch-Janys D, Mutschelknauss E,
Ashton K, Salazar R, Webb E, Hamann U, Brauch H,
Justenhoven C, Ko YD, Brüning T, Silva Idos S, Johnson N,
Pharoah PP, , Pooley KA, Chang-Claude J, Easton DF, Peto
J, Houlston R; Gene Environment Interaction and Breast
Cancer in Germany Group, Kathleen Cuningham Foundation
Consortium for Research into Familial Breast Cancer
Investigators, Australian Ovarian Cancer Study Management
Group, Chenevix-Trench G, Fletcher O, Burwinkel B
(2008) Association of a common AKAP9 variant with breast cancer risk: a collaborative analysis. J Natl Cancer Inst 100: 437-42. [ FIND THIS ARTICLE ONLINE ]
-
Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel
RD, Bairoch A (2003) ExPASy: The proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res 31: 3784-8. [ FIND THIS ARTICLE ONLINE ]
-
Lin JW, Wyszynski M, Madhavan R, Sealock R, Kim
JU, Sheng M (1998) Yotiao, a novel protein of neuromuscular
junction and brain that interacts with specific splice variants of NMDA receptor subunit NR1. J Neurosci 18: 2017-27. [ FIND THIS ARTICLE ONLINE ]
-
Mack JT, Brown CB, Tew KD (2008) ABCA2 as a therapeutic target in cancer and nervous system disorders. Expert Opin Ther Targets 12: 491-504. [ FIND THIS ARTICLE ONLINE ]
-
Marx SO, Kurokawa J (2006) AKAPs as antiarrhythmic targets? Handb Exp Pharmacol 171: 221-33. [ FIND THIS ARTICLE ONLINE ]
-
Rudd MF, Webb EL, Matakidou A, Sellick GS, Williams
RD, Bridle H, Eisen T, Houlston RS; GELCAPS Consortium (2006) Variants in the GH-IGF axis confer susceptibility to lung cancer Genome Res 16: 693-701. [ FIND THIS ARTICLE ONLINE ]
-
Saucerman JJ, Healy SN, Belik ME, Puglisi JL,
McCulloch AD (2004) Proarrhythmic consequences of a
KCNQ1 AKAP-binding domain mutation: computational models of whole cells and heterogeneous tissue Circ Res 95: 1216-24. [ FIND THIS ARTICLE ONLINE ]
-
Shah SC, Kusiak A (2004) Data mining and genetic algorithm based gene/SNP selection. Artif Intell Med 31: 183-96. [ FIND THIS ARTICLE ONLINE ]
-
Tao J, Shumay E, McLaughlin S, Wang HY, Malbon CC (2006) Regulation of AKAP-membrane interactions by calcium. J Biol Chem 281: 23932-44. [ FIND THIS ARTICLE ONLINE ]
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