Epithelial discoidin domain-containing receptor
From Proteopedia
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| - | <StructureSection load='4bkj' size=' | + | <StructureSection load='4bkj' size='400' side='right' caption='Human DDR1 kinase domain complex with imatinib and ethylene glycol (PDB code [[4bkj]])' scene='80/805011/Cv/1'> |
== Function == | == Function == | ||
| - | '''Epithelial discoidin domain-containing receptor''' (DDR1 and DDR2) are extracellular matrix-sensing | + | '''Epithelial discoidin domain-containing receptor''' (DDR1 and DDR2) are extracellular matrix-sensing [[Receptor tyrosine kinases]] which are activated by collagen and are expressed in bronchial epithelium. They are responsible for maintaining the normal structure of skin and kidney epithelia<ref>PMID:20884741</ref>. DDR1 and DDR2 function as sensors for extracellular matrix and to regulate a wide range of cell functions from migration and proliferation to cytokine secretion and extracellular matrix homeostasis/remodeling<ref name = "DDR1">PMID:24361528</ref>. |
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| + | See also [[Kinase-linked, enzyme-linked and related receptors]]. | ||
== Disease == | == Disease == | ||
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== Structural highlights == | == Structural highlights == | ||
| - | DDR1 contains a discoidin domain. This domain is about 150 amino acid long and is found in many blood coagulation factors. The structure of the complex between DDR1 and imatinib shows | + | DDR1 contains a discoidin domain. This domain is about 150 amino acid long and is found in many blood coagulation factors. The structure of the <scene name='80/805011/Cv/3'>complex between DDR1 and imatinib</scene> shows hydrogen bonds interactions between the anti-cancer drug and the kinase domain including bonds with the <scene name='80/805011/Cv/4'>kinase allosteric site Asp-Phe-Gly (DFG motif)</scene><ref>PMID:24768818</ref>. Water molecules are shown as red spheres. |
</StructureSection> | </StructureSection> | ||
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{{#tree:id=OrganizedByTopic|openlevels=0| | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
| - | *Epithelial discoidin domain-containing receptor 1; Domains – discoidin 26-186; ligand-binding 283-385; kinase 543- | + | *Epithelial discoidin domain-containing receptor 1; Domains – discoidin 26-186; ligand-binding 283-385; kinase 543-913 |
| - | **[[5bvk]] – hDDR1 kinase domain | + | **[[5bvk]], [[6y23]] – hDDR1 kinase domain – human<br /> |
| - | **[[3zos]], [[4bkj]] – hDDR1 kinase domain + cancer drug<br /> | + | **[[3zos]], [[4bkj]], [[6bsd]] – hDDR1 kinase domain + cancer drug<br /> |
**[[6few]] – hDDR1 kinase domain + alport syndrome drug<br /> | **[[6few]] – hDDR1 kinase domain + alport syndrome drug<br /> | ||
| - | **[[6fex]], [[6fil | + | **[[6fex]], [[6fil]],[[6fin]], [[6fio]], [[6fiq]] – hDDR1 kinase domain (mutant) + alport syndrome drug<br /> |
| - | **[[4ckr]], [[5bvn]], [[5bvo]], [[5bvw]], [[5fdp]], [[5fdx]], [[6brj]], [[6gwr]] – hDDR1 kinase domain + inhibitor<br /> | + | **[[4ckr]], [[5bvn]], [[5bvo]], [[5bvw]], [[5fdp]], [[5fdx]], [[5sau]], [[5saw]], [[5sax]], [[5say]], [[5saz]], [[5sb0]], [[5sb1]], [[5sb2]], [[6brj]], [[6gwr]], [[6hp9]], [[7bcm]], [[7be6]], [[7feh]] – hDDR1 kinase domain + inhibitor<br /> |
**[[4ag4]] – hDDR1 29-367 domain + antibody<br /> | **[[4ag4]] – hDDR1 29-367 domain + antibody<br /> | ||
| + | **[[8pe9]] – hDDR1 188-370 domain + antibody<br /> | ||
*Epithelial discoidin domain-containing receptor 2 | *Epithelial discoidin domain-containing receptor 2 | ||
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**[[2z4f]] – hDDR2 discoidin domain – NMR<br /> | **[[2z4f]] – hDDR2 discoidin domain – NMR<br /> | ||
**[[2wuh]] – hDDR2 discoidin domain + collagen<br /> | **[[2wuh]] – hDDR2 discoidin domain + collagen<br /> | ||
| - | **[[6fer]] – hDDR2 kinase domain + inhibitor<br /> | + | **[[6fer]], [[7aym]] – hDDR2 kinase domain + inhibitor<br /> |
}} | }} | ||
== References == | == References == | ||
Current revision
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3D structures of epithelial discoidin domain-containing receptor
Updated on 01-June-2025
References
- ↑ Roberts ME, Magowan L, Hall IP, Johnson SR. Discoidin domain receptor 1 regulates bronchial epithelial repair and matrix metalloproteinase production. Eur Respir J. 2011 Jun;37(6):1482-93. doi: 10.1183/09031936.00039710. Epub 2010, Sep 30. PMID:20884741 doi:http://dx.doi.org/10.1183/09031936.00039710
- ↑ 2.0 2.1 Borza CM, Pozzi A. Discoidin domain receptors in disease. Matrix Biol. 2014 Feb;34:185-92. doi: 10.1016/j.matbio.2013.12.002. Epub 2013 Dec, 19. PMID:24361528 doi:http://dx.doi.org/10.1016/j.matbio.2013.12.002
- ↑ Song J, Chen X, Bai J, Liu Q, Li H, Xie J, Jing H, Zheng J. Discoidin domain receptor 1 (DDR1), a promising biomarker, induces epithelial to mesenchymal transition in renal cancer cells. Tumour Biol. 2016 Aug;37(8):11509-21. doi: 10.1007/s13277-016-5021-2. Epub 2016, Mar 28. PMID:27020590 doi:http://dx.doi.org/10.1007/s13277-016-5021-2
- ↑ Toy KA, Valiathan RR, Nunez F, Kidwell KM, Gonzalez ME, Fridman R, Kleer CG. Tyrosine kinase discoidin domain receptors DDR1 and DDR2 are coordinately deregulated in triple-negative breast cancer. Breast Cancer Res Treat. 2015 Feb;150(1):9-18. doi: 10.1007/s10549-015-3285-7., Epub 2015 Feb 10. PMID:25667101 doi:http://dx.doi.org/10.1007/s10549-015-3285-7
- ↑ Canning P, Tan L, Chu K, Lee SW, Gray NS, Bullock AN. Structural mechanisms determining inhibition of the collagen receptor DDR1 by selective and multi-targeted type II kinase inhibitors. J Mol Biol. 2014 Apr 22. pii: S0022-2836(14)00198-3. doi:, 10.1016/j.jmb.2014.04.014. PMID:24768818 doi:http://dx.doi.org/10.1016/j.jmb.2014.04.014
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