Structural highlights
3fy2 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Related: | 3fxx, 1ir3, 2gsf, 2qoc |
| Gene: | EPHA3, ETK, ETK1, HEK, TYRO4 (HUMAN) |
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum |
Disease
[EPHA3_HUMAN] Defects in EPHA3 may be a cause of colorectal cancer (CRC) [MIM:114500].
Function
[EPHA3_HUMAN] Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ephrin receptor tyrosine kinase A3 (EphA3, EC 2.7.10.1) is a member of a unique branch of the kinome in which downstream signaling occurs in both ligand- and receptor-expressing cells. Consequently, the ephrins and ephrin receptor tyrosine kinases often mediate processes involving cell-cell contact, including cellular adhesion or repulsion, developmental remodeling and neuronal mapping. The receptor is also frequently overexpressed in invasive cancers, including breast, small-cell lung and gastrointestinal cancers. However, little is known about direct substrates of EphA3 kinase and no chemical probes are available. Using a library approach, we found a short peptide sequence that is a good substrate for EphA3 and is suitable for co-crystallization studies. Complex structures show multiple contacts between kinase and substrates; in particular, two residues undergo conformational changes and by mutation are found to be important for substrate binding and turnover. In addition, a difference in catalytic efficiency between EPH kinase family members is observed. These results provide insight into the mechanism of substrate binding to these developmentally integral enzymes.
Structural recognition of an optimized substrate for the ephrin family of receptor tyrosine kinases.,Davis TL, Walker JR, Allali-Hassani A, Parker SA, Turk BE, Dhe-Paganon S FEBS J. 2009 Aug;276(16):4395-404. PMID:19678838[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lawrenson ID, Wimmer-Kleikamp SH, Lock P, Schoenwaelder SM, Down M, Boyd AW, Alewood PF, Lackmann M. Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. J Cell Sci. 2002 Mar 1;115(Pt 5):1059-72. PMID:11870224
- ↑ Davis TL, Walker JR, Allali-Hassani A, Parker SA, Turk BE, Dhe-Paganon S. Structural recognition of an optimized substrate for the ephrin family of receptor tyrosine kinases. FEBS J. 2009 Aug;276(16):4395-404. PMID:19678838 doi:http://dx.doi.org/10.1111/j.1742-4658.2009.07147.x
