NKX2.5 Homeodomain

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= General Information =
= General Information =
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The transcription factor, NKX2.5 is one of many proteins classified as a homeodomain, and functions to regulate structural development in eukaryotes. These proteins share a characteristic fold containing three alpha-helices. <ref> Gehring WJ, Affolter M, Burglin T. Homeodomain proteins. Annu Rev Biochem. 1994;63:487–526. </ref>. This evolutionarily conserved structure allows homeodomains to locate and bind specific DNA sequences, leading to transcriptional activation or repression. Furthermore, homeodomain transcription factors act on genes associated with the development of anatomical structures in eukaryotes <ref> Bürglin, T. R., & Affolter, M. (2016). Homeodomain proteins: an update. Chromosoma, 125(3), 497–521. https://doi.org/10.1007/s00412-015-0543-8 </ref>.
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=='''NKX2.5 Homeodomain'''==
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multiple transcription factors that work in conjunction during cardiogenesis <ref> Olson, E. N. (2006) Gene regulatory networks in the evolution and development of the heart. Science 313, 1922−1927. </ref> <ref> Akazawa H, Komuro I. Cardiac transcription factor Csx/Nkx2–5: Its role in cardiac development and diseases. Pharmacol Ther. 2005;107:252–268. </ref>.
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<StructureSection load='3RKQ' size='340' side='right' caption=''NKX2.5 Homeodomain dimer bound to ANF-242''=''>
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= General Information =
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The transcription factor, NKX2.5 is one of many proteins classified as a homeodomain, and functions to regulate structural development in eukaryotes. These proteins share a characteristic evolutionarily conserved fold containing three alpha-helices. <ref> Gehring WJ, Affolter M, Burglin T. Homeodomain proteins. Annu Rev Biochem. 1994;63:487–526. </ref>. This allows homeodomains to locate and bind specific DNA sequences, leading to transcriptional activation or repression. <ref> Bürglin, T. R., & Affolter, M. (2016). Homeodomain proteins: an update. Chromosoma, 125(3), 497–521. https://doi.org/10.1007/s00412-015-0543-8 </ref>. In the case of NKX2.5, the protein works in conjunction with multiple other transcription factors during cardiogenesis <ref> Olson, E. N. (2006) Gene regulatory networks in the evolution and development of the heart. Science 313, 1922−1927. </ref>,<ref> Akazawa H, Komuro I. Cardiac transcription factor Csx/Nkx2–5: Its role in cardiac development and diseases. Pharmacol Ther. 2005;107:252–268. </ref>. Recently, research has been focused on NKX2.5 as mutations in the DNA binding residues, and structural support residues of the protein have been linked to congenital heart disease. Specifically, NKX2.5 mutations have been linked to etiologies involving both atrial and septal defects, deficient atrioventricular node conduction, and more complex mutations such as Tetralogy of Fallot and Hypoplastic Left Heart Syndrome <ref> Toko, H., Zhu, W., Takimoto, E., Shiojima, I., Hiroi, Y., Zou, Y., Oka, T., Akazawa, H., Mizukami, M., Sakamoto, M., Terasaki, F., Kitaura, Y., Takano, H., Nagai, T., Nagai, R., and Komuro, I. (2002) Csx/Nkx2−5 is required for homeostasis and survival of cardiac myocytes in the adult heart. J. Biol. Chem. 277, 24735−24743. </ref>,<ref> Schott, J., Benson, D., Basson, C., Pease, W., Silberbach, G., Moak, J., Maron, B., Seidman, C., and Seidman, J. (1998) Congenital heart disease caused by mutations in the transcription factor NKX2−5. Science 281, 108−111. </ref>,<ref> McElhinney, D. B., Geiger, E., Blinder, J., Benson, D. W., & Goldmuntz, E. (2003). NKX2.5 mutations in patients with congenital heart disease. Journal of the American College of Cardiology, 42(9), 1650–1655. https://doi.org/10.1016/j.jacc.2003.05.004 </ref>. These phenotypes are speculated to arise as a result of decreased
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=== Clinical Relevance ===
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== Protein / DNA Interactions ==
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Scene <scene name='91/911264/Test/1'>wicked cool scene</scene>
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=== Mutational Analysis ===
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= Protein / DNA interactions =
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== Structural highlights ==
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</StructureSection>
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== References ==
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<references/>
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=== Clinical Relevance ===
=== Clinical Relevance ===

Revision as of 01:44, 3 May 2022

Contents

NKX2.5 Homeodomain

PDB ID 3RKQ

Drag the structure with the mouse to rotate

References

  1. ↑ Gehring WJ, Affolter M, Burglin T. Homeodomain proteins. Annu Rev Biochem. 1994;63:487–526.
  2. ↑ Bürglin, T. R., & Affolter, M. (2016). Homeodomain proteins: an update. Chromosoma, 125(3), 497–521. https://doi.org/10.1007/s00412-015-0543-8
  3. ↑ Olson, E. N. (2006) Gene regulatory networks in the evolution and development of the heart. Science 313, 1922−1927.
  4. ↑ Akazawa H, Komuro I. Cardiac transcription factor Csx/Nkx2–5: Its role in cardiac development and diseases. Pharmacol Ther. 2005;107:252–268.
  5. ↑ Toko, H., Zhu, W., Takimoto, E., Shiojima, I., Hiroi, Y., Zou, Y., Oka, T., Akazawa, H., Mizukami, M., Sakamoto, M., Terasaki, F., Kitaura, Y., Takano, H., Nagai, T., Nagai, R., and Komuro, I. (2002) Csx/Nkx2−5 is required for homeostasis and survival of cardiac myocytes in the adult heart. J. Biol. Chem. 277, 24735−24743.
  6. ↑ Schott, J., Benson, D., Basson, C., Pease, W., Silberbach, G., Moak, J., Maron, B., Seidman, C., and Seidman, J. (1998) Congenital heart disease caused by mutations in the transcription factor NKX2−5. Science 281, 108−111.
  7. ↑ McElhinney, D. B., Geiger, E., Blinder, J., Benson, D. W., & Goldmuntz, E. (2003). NKX2.5 mutations in patients with congenital heart disease. Journal of the American College of Cardiology, 42(9), 1650–1655. https://doi.org/10.1016/j.jacc.2003.05.004

Clinical Relevance

Protein / DNA Interactions

Scene

Mutational Analysis

Protein / DNA interactions

Structural highlights

</StructureSection>

References

Proteopedia Page Contributors and Editors (what is this?)

William J Simard, Michal Harel

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