TARGETID

T70234

FORMERID

TTDI02377

UNIPROID

EPHA4_HUMAN

TARGNAME

Ephrin type-A receptor 4 (EPHA4)

GENENAME

EPHA4

TARGTYPE

Literature-reported target

SYNONYMS

hEK8; Tyrosineprotein kinase receptor SEK; Tyrosineprotein kinase TYRO1; Tyrosine-protein kinase receptor SEK; Tyrosine-protein kinase TYRO1; TYRO1; SEK; Ephrin typeA receptor 4; EPHlike kinase 8; EPH-like kinase 8; EK8

FUNCTION

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, plays also 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. Receptor tyrosine kinase which binds membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells.

PDBSTRUC

5JR2; 4W50; 4W4Z; 4M4R; 4M4P

BIOCLASS

Kinase

ECNUMBER

EC 2.7.10.1

SEQUENCE

MAGIFYFALFSCLFGICDAVTGSRVYPANEVTLLDSRSVQGELGWIASPLEGGWEEVSIMDEKNTPIRTYQVCNVMEPSQNNWLRTDWITREGAQRVYIEIKFTLRDCNSLPGVMGTCKETFNLYYYESDNDKERFIRENQFVKIDTIAADESFTQVDIGDRIMKLNTEIRDVGPLSKKGFYLAFQDVGACIALVSVRVFYKKCPLTVRNLAQFPDTITGADTSSLVEVRGSCVNNSEEKDVPKMYCGADGEWLVPIGNCLCNAGHEERSGECQACKIGYYKALSTDATCAKCPPHSYSVWEGATSCTCDRGFFRADNDAASMPCTRPPSAPLNLISNVNETSVNLEWSSPQNTGGRQDISYNVVCKKCGAGDPSKCRPCGSGVHYTPQQNGLKTTKVSITDLLAHTNYTFEIWAVNGVSKYNPNPDQSVSVTVTTNQAAPSSIALVQAKEVTRYSVALAWLEPDRPNGVILEYEVKYYEKDQNERSYRIVRTAARNTDIKGLNPLTSYVFHVRARTAAGYGDFSEPLEVTTNTVPSRIIGDGANSTVLLVSVSGSVVLVVILIAAFVISRRRSKYSKAKQEADEEKHLNQGVRTYVDPFTYEDPNQAVREFAKEIDASCIKIEKVIGVGEFGEVCSGRLKVPGKREICVAIKTLKAGYTDKQRRDFLSEASIMGQFDHPNIIHLEGVVTKCKPVMIITEYMENGSLDAFLRKNDGRFTVIQLVGMLRGIGSGMKYLSDMSYVHRDLAARNILVNSNLVCKVSDFGMSRVLEDDPEAAYTTRGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVIKAIEEGYRLPPPMDCPIALHQLMLDCWQKERSDRPKFGQIVNMLDKLIRNPNSLKRTGTESSRPNTALLDPSSPEFSAVVSVGDWLQAIKMDRYKDNFTAAGYTTLEAVVHVNQEDLARIGITAITHQNKILSSVQAMRTQMQQMHGRMVPV

DRUGINFO

MEDI-542

DRUGINFO

PMID19788238C66

DRUGINFO

PMID23489211C20

KEGGPATH

hsa04360:Axon guidance

WIKIPATH

WP2431:Spinal Cord Injury

WIKIPATH

WP2854:Gene regulatory network modelling somitogenesis

REACPATH

R-HSA-2682334:EPH-Ephrin signaling

REACPATH

R-HSA-3928663:EPHA-mediated growth cone collapse