EPHA4 - Ephrin type-A receptor 4 - human protein (Function)
 
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EPHA4 »  Ephrin type-A receptor 4   [ EC 2.7.10.1 ]
 
Protein also known as:  Tyrosine-protein kinase receptor SEK.
Gene name:  EPHA4
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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. Beside 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.  
1
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
DH domain bindingdefinition[GO:0097161]  
1
  • IDAUniProtKB
Ephrin receptor bindingdefinition[GO:0046875] silver  
  • IEAOrtholog Compara
GPI-linked ephrin receptor activitydefinition[GO:0005004]  
  • ISSOrtholog Curator
Identical protein bindingdefinition[GO:0042802] silver  
  • IEAOrtholog Compara
PH domain bindingdefinition[GO:0042731]  
1
  • IPIUniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • IPIUniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • IDAUniProtKB
Transmembrane-ephrin receptor activitydefinition[GO:0005005]  
  • ISSOrtholog Curator
GO biological process 
Adult walking behaviordefinition[GO:0007628] silver  
  • IEAOrtholog Compara
Cell adhesiondefinition[GO:0007155]  
  • IEAUniProtKB KW
Corticospinal tract morphogenesisdefinition[GO:0021957]  
  • ISSOrtholog Curator
Fasciculation of motor neuron axondefinition[GO:0097156]  
  • ISSOrtholog Curator
Fasciculation of sensory neuron axondefinition[GO:0097155]  
  • ISSOrtholog Curator
Glial cell migrationdefinition[GO:0008347] silver  
  • IEAOrtholog Compara
Motor neuron axon guidancedefinition[GO:0008045]  
  • ISSOrtholog Curator
Negative regulation of axon regenerationdefinition[GO:0048681]  
  • ISSOrtholog Curator
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
1
  • IDAUniProtKB
Positive regulation of dendrite morphogenesisdefinition[GO:0050775] silver  
  • IEAOrtholog Compara
Positive regulation of JUN kinase activitydefinition[GO:0043507] silver  
  • IEAOrtholog Compara
Positive regulation of Rho guanyl-nucleotide exchange factor activitydefinition[GO:2001108]  
1
  • IDAUniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDAUniProtKB
Regulation of astrocyte differentiationdefinition[GO:0048710]  
  • ISSOrtholog Curator
Regulation of axonogenesisdefinition[GO:0050770]  
  • ISSOrtholog Curator
Regulation of dendritic spine morphogenesisdefinition[GO:0061001]  
  • ISSOrtholog Curator
Regulation of Rac GTPase activitydefinition[GO:0032314]  
  • ISSOrtholog Curator
Regulation of Rap GTPase activitydefinition[GO:0032317]  
  • ISSOrtholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.1: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathway:
Axon guidance  hsa04360+2043  
 

Keywords

Biological process 
Cell adhesion  definition   [KW-0130]
Neurogenesis  definition   [KW-0524]
Molecular function 
Developmental protein  definition   [KW-0217]
Kinase  definition   [KW-0418]
Receptor  definition   [KW-0675]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: EPH_receptor_A4
GenomeRNAi: 2043
PRO: PR:P54764
Chemistry
GuidetoPHARMACOLOGY: 1824