Ephrin type-A receptor 3
Also known as: EPHA3, ETK, ETK1, HEK, TYRO4
Function
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 (By similarity). Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Also activated by EFNA1, inhibiting epithelial-to-mesenchymal transition of cardiac cells and playing a role in heart development. 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 (By similarity).
Classification
- Family (Pfam)
- PF14575 EphA2_TM, PF25599 Ephrin_CRD, PF01404 Ephrin_lbd, PF07699 Ephrin_rec_like, PF00041 fn3, PF07714 PK_Tyr_Ser-Thr, PF07647 SAM_2
- InterPro
- Eph_TM, EphA3_rcpt_lig-bd, Ephrin_rcpt_lig-bd_dom, Ephrin_rcpt_TKs, FN3_dom, FN3_sf, Galactose-bd-like_sf, Growth_fac_rcpt_cys_sf, Ig-like_fold, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, SAM, SAM/pointed_sf, Ser-Thr/Tyr_kinase_cat_dom, Tyr-kin_ephrin_A/B_rcpt-like, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_ephrin_rcpt, Tyr_kinase_rcpt_V_CS
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 28
- 2GSF X-ray 1.77A
- 2QO2 X-ray 1.60A
- 2QO7 X-ray 1.60A
- 2QO9 X-ray 1.55A
- 2QOB X-ray 1.65A
- 2QOC X-ray 1.25A
- 2QOD X-ray 1.15A
- 2QOF X-ray 1.20A
- 2QOI X-ray 1.25A
- 2QOK X-ray 1.20A
- 2QOL X-ray 1.07A
- 2QON X-ray 1.79A
- … and 16 more
A predicted model is available from AlphaFold.
Gene Ontology · 25
- GO:0030425 dendrite
- GO:0005769 early endosome
- GO:0005576 extracellular region
- GO:0005886 plasma membrane
- GO:0005524 ATP binding
- GO:0005003 ephrin receptor activity
- GO:0005004 GPI-linked ephrin receptor activity
- GO:0005005 transmembrane-ephrin receptor activity
- GO:0007411 axon guidance
- GO:0007155 cell adhesion
- GO:0016477 cell migration
- GO:0071300 cellular response to retinoic acid
- GO:0048013 ephrin receptor signaling pathway
- GO:0097156 fasciculation of motor neuron axon
- GO:0097155 fasciculation of sensory neuron axon
- GO:0045806 negative regulation of endocytosis
- GO:0010719 negative regulation of epithelial to mesenchymal transition
- GO:0018108 peptidyl-tyrosine phosphorylation
- GO:0010976 positive regulation of neuron projection development
- GO:1903078 positive regulation of protein localization to plasma membrane
- GO:0032956 regulation of actin cytoskeleton organization
- GO:0022407 regulation of cell-cell adhesion
- GO:0010717 regulation of epithelial to mesenchymal transition
- GO:0051893 regulation of focal adhesion assembly
- GO:0070507 regulation of microtubule cytoskeleton organization
Disease associations
- colorectal cancer MONDO:0005575
Drugs targeting this protein · 1
- VANDETANIB inhibitor
Related proteins · sequence + function similarity
- Ephrin type-A receptor 3 1.00
- Ephrin type-A receptor 3 0.99
- Ephrin type-A receptor 3 0.98
- Ephrin type-A receptor 4-B 0.95
- Ephrin type-A receptor 4 0.95
- Ephrin type-A receptor 4 0.95
- Ephrin type-B receptor 1 0.95
- Ephrin type-A receptor 7 0.95
- Ephrin type-B receptor 1 0.95
- Ephrin type-A receptor 4 0.95
- Ephrin type-A receptor 4-A 0.95
- Ephrin type-B receptor 1 0.95
Co-cited proteins · studied together in the literature
- Ephrin-A1 1 shared papers
- Tyrosine-protein phosphatase non-receptor type 1 1 shared papers
- Ephrin-A5 2 shared papers
- Disintegrin and metalloproteinase domain-containing protein 10 1 shared papers
- Ephrin type-A receptor 3 1 shared papers
- Adapter molecule crk 1 shared papers
- Ephrin type-A receptor 7 1 shared papers
- Ephrin type-B receptor 3 1 shared papers
- Disintegrin and metalloproteinase domain-containing protein 10 1 shared papers
- Ephrin type-A receptor 5 1 shared papers
- Adapter molecule crk 1 shared papers
- Ephrin type-A receptor 1 1 shared papers
Literature · 16 cited papers
- PTP1B regulates Eph receptor function and trafficking. J. Cell Biol. · 2010
- Mutational profiling of kinases in human tumours of pancreatic origin identifies candidate cancer genes in ductal and ampulla of vater carcinomas. PLoS ONE · 2010
- Autoregulation by the juxtamembrane region of the human ephrin receptor tyrosine kinase A3 (EphA3). Structure · 2008
- Patterns of somatic mutation in human cancer genomes. Nature · 2007
- The consensus coding sequences of human breast and colorectal cancers. Science · 2006
- Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers. Hum. Mutat. · 2006
- Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell · 2005
- Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3. J. Biol. Chem. · 2005
- Dissecting the EphA3/Ephrin-A5 interactions using a novel functional mutagenesis screen. J. Biol. Chem. · 2004
- Ephrin-A1 induces c-Cbl phosphorylation and EphA receptor down-regulation in T cells. J. Immunol. · 2003
- Mutational analysis of the tyrosine kinome in colorectal cancers. Science · 2003
- 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
- … and 4 more in the literature graph
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