NKX2.5 Homeodomain

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[[Image:Map.png |thumb|right|upright=3.5|''Organization of the biological protein NKX2.5. The structures analyzed only represent the homeodomain region.'']]
[[Image:Map.png |thumb|right|upright=3.5|''Organization of the biological protein NKX2.5. The structures analyzed only represent the homeodomain region.'']]
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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 <scene name='91/911264/Three_alpha_helices/2'>three alpha-helices</scene>. <ref name="WJ"> PMID: 7979246 </ref>. DNA-binding is mediated through the insertion of the C-terminal side <scene name='91/911264/Major_groove_interaction/4'>alpha-helix</scene> (alpha-3) into the major groove, allowing for base-reside interactions. This allows homeodomains to locate and bind specific DNA sequences, leading to transcriptional activation or repression <ref> PMID: 26464018 </ref>. The homeodomain of NKX2.5 is flanked by both a N and C-terminal regulatory domain. This puts the biological protein at 324 residues with the homeodomain consisting of residues 138-197 <ref> PMID: 22849347 </ref> Research into the structure and function of NKX2.5 has mainly been focused on the DNA-binding homeodomain, as mutations in this region have been linked to specific diseases <ref name="Schott"> PMID: 9651244</ref>. This page will focus on the specific interactions of the homeodomain of NKX2.5 with DNA, and how these interactions relate to one of the transcription factor's primary function - heart development.
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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 <scene name='91/911264/Three_alpha_helices/2'>three alpha-helices</scene>. <ref name="WJ"> PMID: 7979246 </ref>. DNA-binding is mediated through the insertion of the C-terminal side <scene name='91/911264/Major_groove_interaction/4'>alpha-helix</scene> (alpha-3) into the major groove, allowing for base-reside interactions. This allows homeodomains to locate and bind specific DNA sequences, leading to transcriptional activation or repression <ref> PMID: 26464018 </ref>. The homeodomain of NKX2.5 is flanked by both a N and C-terminal regulatory domain. This puts the biological protein at 324 residues with the homeodomain consisting of residues 138-197 <ref> PMID: 22849347 </ref> Research into the structure and function of NKX2.5 has mainly been focused on the DNA-binding homeodomain, as mutations in this region have been linked to specific diseases <ref name="Schott"> PMID: 9651244</ref>. This page will focus on the specific interactions of the homeodomain of NKX2.5 with DNA, and how these interactions relate to one of the transcription factor's primary function - heart development.
= Clinical Relevance =
= Clinical Relevance =
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[[Image:Sequence2.png|thumb|right|upright=4|''Sequence alignment of NKX2.5 isoforms from multiple species. Red boxes indicate the continuous homeodomain region from residue 137-194.'']]
[[Image:Sequence2.png|thumb|right|upright=4|''Sequence alignment of NKX2.5 isoforms from multiple species. Red boxes indicate the continuous homeodomain region from residue 137-194.'']]
It is important to note that the residues involved in the recognition of the NKX2.5 motif are fully conserved across all isoforms. The cross-species similarities in NKX2.5 isozymes is of special importance in relation to research. For example, ''Danio rerio'' (Zebrafish) have been used as models to study heart development during gestation <ref> PMID: 10993952 </ref>, <ref> PMID: 28615160 </ref>. This is made possible by the fact that the ''Danio rerio'' and ''Homo sapien'' NKX2.5 share sequence similarities.
It is important to note that the residues involved in the recognition of the NKX2.5 motif are fully conserved across all isoforms. The cross-species similarities in NKX2.5 isozymes is of special importance in relation to research. For example, ''Danio rerio'' (Zebrafish) have been used as models to study heart development during gestation <ref> PMID: 10993952 </ref>, <ref> PMID: 28615160 </ref>. This is made possible by the fact that the ''Danio rerio'' and ''Homo sapien'' NKX2.5 share sequence similarities.
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=Homeobox protein Nkx-2.5 3D structures=
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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[[3rkq]] – hNkx-2.5 + DNA – human <br />
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[[6wc2]], [[6wc5]] – hNkx-2.5 + myocyte-specific enhancer factor 2B + DNA <br />
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[[4s0h]] – hNkx-2.5 + TBX5 + DNA <br />
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[[5flv]] – Nkx-2.5 + TBX5 + DNA - mouse<br />
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[[2l9r]] – hNkx-3.1 - NMR <br />
= References =
= References =
<references/>
<references/>
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[[Category:Topic Page]]

Current revision

PDB ID 3rkq

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Proteopedia Page Contributors and Editors (what is this?)

William J Simard, Michal Harel

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