Names & Taxonomy
- Uniprot ID:
- P54764
- Entry Name:
- EPHA4_HUMAN
- Status:
- reviewed
- Protein Names:
- Ephrin type-A receptor 4 (EC 2.7.10.1) (EPH-like kinase 8) (EK8) (hEK8) (Tyrosine-protein kinase TYRO1) (Tyrosine-protein kinase receptor SEK)
- Gene Names:
- EPHA4 HEK8 SEK TYRO1
- Gene Names Primary:
- EPHA4
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 986
- Sequence:
- MAGIFYFALFSCLFGICDAVTGSRVYPANEVTLLDSRSVQGELGWIASPLEGGWEEVSIMDEKNTPIRTYQVCNVMEPSQNNWLRTDWITREGAQRVYIEIKFTLRDCNSLPGVMGTCKETFNLYYYESDNDKERFIRENQFVKIDTIAADESFTQVDIGDRIMKLNTEIRDVGPLSKKGFYLAFQDVGACIALVSVRVFYKKCPLTVRNLAQFPDTITGADTSSLVEVRGSCVNNSEEKDVPKMYCGADGEWLVPIGNCLCNAGHEERSGECQACKIGYYKALSTDATCAKCPPHSYSVWEGATSCTCDRGFFRADNDAASMPCTRPPSAPLNLISNVNETSVNLEWSSPQNTGGRQDISYNVVCKKCGAGDPSKCRPCGSGVHYTPQQNGLKTTKVSITDLLAHTNYTFEIWAVNGVSKYNPNPDQSVSVTVTTNQAAPSSIALVQAKEVTRYSVALAWLEPDRPNGVILEYEVKYYEKDQNERSYRIVRTAARNTDIKGLNPLTSYVFHVRARTAAGYGDFSEPLEVTTNTVPSRIIGDGANSTVLLVSVSGSVVLVVILIAAFVISRRRSKYSKAKQEADEEKHLNQGVRTYVDPFTYEDPNQAVREFAKEIDASCIKIEKVIGVGEFGEVCSGRLKVPGKREICVAIKTLKAGYTDKQRRDFLSEASIMGQFDHPNIIHLEGVVTKCKPVMIITEYMENGSLDAFLRKNDGRFTVIQLVGMLRGIGSGMKYLSDMSYVHRDLAARNILVNSNLVCKVSDFGMSRVLEDDPEAAYTTRGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVIKAIEEGYRLPPPMDCPIALHQLMLDCWQKERSDRPKFGQIVNMLDKLIRNPNSLKRTGTESSRPNTALLDPSSPEFSAVVSVGDWLQAIKMDRYKDNFTAAGYTTLEAVVHVNQEDLARIGITAITHQNKILSSVQAMRTQMQQMHGRMVPV
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cell membrane
Function
- 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, 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.
- Catalytic Activity:
- ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
- Active Site:
- ACT_SITE 746 746 Proton acceptor.
- Gene Ontology Go:
- axon
axon terminus
axonal growth cone
cell junction
cell surface
cytoplasm
dendrite
dendritic spine
early endosome membrane
endoplasmic reticulum
filopodium
Golgi apparatus
integral component of plasma membrane
mitochondrial outer membrane
neuromuscular junction
perikaryon
plasma membrane
postsynaptic density
postsynaptic membrane
ATP binding
DH domain binding
GPI-linked ephrin receptor activity
PH domain binding
protein kinase activity
transmembrane-ephrin receptor activity
adult walking behavior
axon guidance
cell adhesion
corticospinal tract morphogenesis
ephrin receptor signaling pathway
fasciculation of motor neuron axon
fasciculation of sensory neuron axon
glial cell migration
motor neuron axon guidance
negative regulation of axon regeneration
nephric duct morphogenesis
peptidyl-tyrosine phosphorylation
positive regulation of dendrite morphogenesis
positive regulation of JUN kinase activity
positive regulation of Rho guanyl-nucleotide exchange factor activity
protein autophosphorylation
regulation of astrocyte differentiation
regulation of axonogenesis
regulation of dendritic spine morphogenesis
regulation of GTPase activity - Gene Ontology Biological Process:
- adult walking behavior
axon guidance
cell adhesion
corticospinal tract morphogenesis
ephrin receptor signaling pathway
fasciculation of motor neuron axon
fasciculation of sensory neuron axon
glial cell migration
motor neuron axon guidance
negative regulation of axon regeneration
nephric duct morphogenesis
peptidyl-tyrosine phosphorylation
positive regulation of dendrite morphogenesis
positive regulation of JUN kinase activity
positive regulation of Rho guanyl-nucleotide exchange factor activity
protein autophosphorylation
regulation of astrocyte differentiation
regulation of axonogenesis
regulation of dendritic spine morphogenesis
regulation of GTPase activity - Gene Ontology Molecular Function:
- ATP binding
DH domain binding
GPI-linked ephrin receptor activity
PH domain binding
protein kinase activity
transmembrane-ephrin receptor activity - Gene Ontology Cellular Component:
- axon
axonal growth cone
axon terminus
cell junction
cell surface
cytoplasm
dendrite
dendritic spine
early endosome membrane
endoplasmic reticulum
filopodium
Golgi apparatus
integral component of plasma membrane
mitochondrial outer membrane
neuromuscular junction
perikaryon
plasma membrane
postsynaptic density
postsynaptic membrane - Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Cell adhesion
Cell junction
Cell membrane
Cell projection
Complete proteome
Developmental protein
Endosome
Glycoprotein
Kinase
Membrane
Neurogenesis
Nucleotide-binding
Phosphoprotein
Polymorphism
Postsynaptic cell membrane
Receptor
Reference proteome
Repeat
Signal
Synapse
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase