| Primary Identifier | IPR030602 | Type | Domain |
| Short Name | EphA4_SAM |
| description | This entry represents the SAM domain of EPH-A4. It is a C-terminal potential protein-protein interaction domain [].Ephrin receptors (Ephs) are a group of receptor tyrosine kinases that are activated in response to binding ephrin ligands residing on adjacent cells, leading to contact-dependent bidirectional signalling into neighbouring cells [].Ephrin type-A receptor 4 (EphA4) is highly promiscuou; 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 []. It is involved in development [, ], supporting spine maturation [, , ], axon guidance [, ]and assembly of neuronal locomotor circuits [, ]. EphA4 is the most abundant ephrin receptor in the nervous system. Mice lacking the EphA4 exhibit pronounced axonal regeneration and functional recovery following spinal cord injury [, , ]. In humans EphA4 has been proposed to be a key actor in neurodegenerative diseases, such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS) []. Inhibition of the EphA4-ephrin interaction has been considered as a useful strategy for promoting axon regeneration in the nervous system and a pharmacological tool to treat neurodegenerative disease patients [, ]. EphA4 also plays a role in human cancers. Overexpression of EphA4 is observed in many human cancers []. For instance, overexpression of EphA4 is associated with gastric cancer invasion and recurrence []. Antagonising Eph-ephrin interactions by interfering with the Eph receptor/ephrin system has been suggested to be used in anti-angiogenic cancer therapies [, ]. EphA4 is also a potent negative regulator of osteoclastic activity []. |
