EPHA4
Ephrin type-A receptor 4
Also known as: EPHA4_HUMAN, Hek8, TYRO1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P54764
- Gene
- EPHA4
- Ensembl
- ENSG00000116106
- Chromosome
- 2
- Canonical length
- 986 aa
- Protein class
- Cancer-related genes, Enzymes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins
OverviewNCBI Gene
This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]
Canonical amino-acid sequenceUniProt
986 residues, UniProt reviewed canonical sequence.
>P54764|EPHA4
1 MAGIFYFALF SCLFGICDAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL EGGWEEVSIM
61 DEKNTPIRTY QVCNVMEPSQ NNWLRTDWIT REGAQRVYIE IKFTLRDCNS LPGVMGTCKE
121 TFNLYYYESD NDKERFIREN QFVKIDTIAA DESFTQVDIG DRIMKLNTEI RDVGPLSKKG
181 FYLAFQDVGA CIALVSVRVF YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK
241 DVPKMYCGAD GEWLVPIGNC LCNAGHEERS GECQACKIGY YKALSTDATC AKCPPHSYSV
301 WEGATSCTCD RGFFRADNDA ASMPCTRPPS APLNLISNVN ETSVNLEWSS PQNTGGRQDI
361 SYNVVCKKCG AGDPSKCRPC GSGVHYTPQQ NGLKTTKVSI TDLLAHTNYT FEIWAVNGVS
421 KYNPNPDQSV SVTVTTNQAA PSSIALVQAK EVTRYSVALA WLEPDRPNGV ILEYEVKYYE
481 KDQNERSYRI VRTAARNTDI KGLNPLTSYV FHVRARTAAG YGDFSEPLEV TTNTVPSRII
541 GDGANSTVLL VSVSGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF
601 TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV AIKTLKAGYT
661 DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE YMENGSLDAF LRKNDGRFTV
721 IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR NILVNSNLVC KVSDFGMSRV LEDDPEAAYT
781 TRGGKIPIRW TAPEAIAYRK FTSASDVWSY GIVMWEVMSY GERPYWDMSN QDVIKAIEEG
841 YRLPPPMDCP IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR TGTESSRPNT
901 ALLDPSSPEF SAVVSVGDWL QAIKMDRYKD NFTAAGYTTL EAVVHVNQED LARIGITAIT
961 HQNKILSSVQ AMRTQMQQMH GRMVPVLocalizationUniProt · AlphaFold · HPA
Whether an antibody against EPHA4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 1
- Mean surface accessibility (rSASA)
- 0.32
- Highest tissue expression
- 24 nTPM
Expression across tissuesHPA
Tissue
- cerebral cortex: 24 nTPM
- heart muscle: 16 nTPM
- skin: 12 nTPM
- testis: 11 nTPM
- ovary: 9.7 nTPM
- thyroid gland: 8.9 nTPM
Single-cell type
- choroid plexus epithelial cells: 872 nCPM
- sertoli cells: 556 nCPM
- brain excitatory neurons: 270 nCPM
- pituicytes/fscs: 256 nCPM
- vascular endothelial cells: 230 nCPM
- retinal ganglion cells: 162 nCPM
Immune cell
- NK-cell: 3.5 nTPM
- memory CD4 T-cell: 2.5 nTPM
- gdT-cell: 1.7 nTPM
- MAIT T-cell: 1.7 nTPM
- memory CD8 T-cell: 1.7 nTPM
- basophil: 1.6 nTPM
Brain region
- choroid plexus: 162 nTPM
- cerebral cortex: 133 nTPM
- hippocampal formation: 124 nTPM
- basal ganglia: 78 nTPM
- thalamus: 75 nTPM
- white matter: 55 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about EPHA4.
Disease | GeneticClinVar
2 pathogenic / likely-pathogenic of 299 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- atypical cerebral palsy
- See cases
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.18
- gnomAD pLI
- 1
- gnomAD missense Z
- 2.89
- DepMap mean gene effect
- 0.05
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- adherens junction organization
- adult walking behavior
- axon guidance
- cell adhesion
- cellular response to amyloid-beta
- cochlea development
- corticospinal tract morphogenesis
- ephrin receptor signaling pathway
- fasciculation of motor neuron axon
- fasciculation of sensory neuron axon
- glial cell migration
- innervation
- motor neuron axon guidance
- negative regulation of axon regeneration
- negative regulation of cell adhesion
- negative regulation of cell migration
- negative regulation of cellular response to hypoxia
- negative regulation of epithelial to mesenchymal transition
- negative regulation of ERK1 and ERK2 cascade
- negative regulation of long-term synaptic potentiation
- negative regulation of neuron apoptotic process
- negative regulation of neuron projection development
- negative regulation of proteolysis involved in protein catabolic process
- negative regulation of translation
- nephric duct morphogenesis
- neuron projection guidance
- positive regulation of amyloid precursor protein catabolic process
- positive regulation of amyloid-beta formation
- positive regulation of cell adhesion
- positive regulation of cell migration
- positive regulation of cell population proliferation
- positive regulation of dendrite morphogenesis
- positive regulation of intracellular signal transduction
- positive regulation of JNK cascade
- positive regulation of leukocyte adhesion to arterial endothelial cell
- protein stabilization
- regulation of astrocyte differentiation
- regulation of axonogenesis
- regulation of dendritic spine morphogenesis
- regulation of GTPase activity
- regulation of modification of synaptic structure
- regulation of synapse pruning
- synapse pruning
- neuron projection fasciculation
Molecular functions
- amyloid-beta binding
- ATP binding
- ephrin receptor activity
- ephrin receptor binding
- GPI-linked ephrin receptor activity
- identical protein binding
- kinase activity
- PH domain binding
- protein tyrosine kinase activity
- protein tyrosine kinase binding
- transmembrane-ephrin receptor activity
- DH domain binding
Cellular components
- adherens junction
- axon
- axon terminus
- axonal growth cone
- cell surface
- cytoplasm
- dendrite
- dendritic shaft
- dendritic spine
- early endosome membrane
- filopodium
- glutamatergic synapse
- mitochondrial outer membrane
- neuromuscular junction
- perikaryon
- plasma membrane
- postsynaptic density membrane
- presynaptic membrane
- Schaffer collateral - CA1 synapse
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- Ephrin, ligand binding domain
- Serine-threonine/tyrosine-protein kinase, catalytic domain
- Tyrosine-protein kinase, receptor class V, conserved site
- Sterile alpha motif domain
- Fibronectin type III
- Tyrosine-protein kinase, active site
- Galactose-binding-like domain superfamily
- Protein kinase-like domain superfamily
- Sterile alpha motif/pointed domain superfamily
- Immunoglobulin-like fold
- Ephrin receptor type-A /type-B
- Protein kinase, ATP binding site
- Tyrosine-protein kinase, catalytic domain
- Ephrin, transmembrane domain
- Fibronectin type III superfamily
- Ephrin receptor tyrosine kinases
- Fibronectin type III domain
- Ephrin receptor ligand binding domain
- SAM domain (Sterile alpha motif)
- Protein tyrosine and serine/threonine kinase
- Ephrin type-A receptor 2 transmembrane domain
- Ephrin cysteine rich domain
- Ephrin type-A receptor 4, SAM domain
- Ephrin type-A receptor 4, ligand binding domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of EPHA4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads EPHA4 as an antibody target. Whether an autoantibody or antibody against EPHA4 could matter depends on whether native EPHA4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
EPHA4 is annotated at the cell surface, where native EPHA4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label EPHA4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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