lmmol · Proteins

Ephrin type-A receptor 4

UniProt P54764 Organism Homo sapiens Gene EPHA4, HEK8, SEK, TYRO1 EC 2.7.10.1

Also known as: EPHA4, HEK8, SEK, TYRO1

Function

Receptor tyrosine kinase which binds 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, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, also plays a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. During development of the cochlear organ of Corti, regulates pillar cell separation by forming a ternary complex with ADAM10 and CADH1 which facilitates the cleavage of CADH1 by ADAM10 and disruption of adherens junctions (By similarity). Phosphorylates CAPRIN1, promoting CAPRIN1-dependent formation of a membraneless compartment (By similarity).

Classification

Family (Pfam)
PF14575 EphA2_TM, PF25599 Ephrin_CRD, PF01404 Ephrin_lbd, PF00041 fn3, PF07714 PK_Tyr_Ser-Thr, PF07647 SAM_2
InterPro
Eph_TM, EphA4_rcpt_lig-bd, EphA4_SAM, Ephrin_rcpt_lig-bd_dom, Ephrin_rcpt_TKs, FN3_dom, FN3_sf, Galactose-bd-like_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_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 · 17

A predicted model is available from AlphaFold.

Gene Ontology · 71

Drugs targeting this protein · 1

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 12 cited papers

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