EPHA3

Protein identityUniProt · HPA

UniProt accession

P29320

Gene

EPHA3

Ensembl

ENSG00000044524

Chromosome

3

Canonical length

983 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Nuclear membrane,Plasma membrane,Actin filaments,Cytosol

Secretome location

Intracellular and membrane

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. This gene encodes a protein that binds ephrin-A ligands. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

983 residues, UniProt reviewed canonical sequence.

>P29320|EPHA3
     1  MDCQLSILLL LSCSVLDSFG ELIPQPSNEV NLLDSKTIQG ELGWISYPSH GWEEISGVDE
    61  HYTPIRTYQV CNVMDHSQNN WLRTNWVPRN SAQKIYVELK FTLRDCNSIP LVLGTCKETF
   121  NLYYMESDDD HGVKFREHQF TKIDTIAADE SFTQMDLGDR ILKLNTEIRE VGPVNKKGFY
   181  LAFQDVGACV ALVSVRVYFK KCPFTVKNLA MFPDTVPMDS QSLVEVRGSC VNNSKEEDPP
   241  RMYCSTEGEW LVPIGKCSCN AGYEERGFMC QACRPGFYKA LDGNMKCAKC PPHSSTQEDG
   301  SMNCRCENNY FRADKDPPSM ACTRPPSSPR NVISNINETS VILDWSWPLD TGGRKDVTFN
   361  IICKKCGWNI KQCEPCSPNV RFLPRQFGLT NTTVTVTDLL AHTNYTFEID AVNGVSELSS
   421  PPRQFAAVSI TTNQAAPSPV LTIKKDRTSR NSISLSWQEP EHPNGIILDY EVKYYEKQEQ
   481  ETSYTILRAR GTNVTISSLK PDTIYVFQIR ARTAAGYGTN SRKFEFETSP DSFSISGESS
   541  QVVMIAISAA VAIILLTVVI YVLIGRFCGY KSKHGADEKR LHFGNGHLKL PGLRTYVDPH
   601  TYEDPTQAVH EFAKELDATN ISIDKVVGAG EFGEVCSGRL KLPSKKEISV AIKTLKVGYT
   661  EKQRRDFLGE ASIMGQFDHP NIIRLEGVVT KSKPVMIVTE YMENGSLDSF LRKHDAQFTV
   721  IQLVGMLRGI ASGMKYLSDM GYVHRDLAAR NILINSNLVC KVSDFGLSRV LEDDPEAAYT
   781  TRGGKIPIRW TSPEAIAYRK FTSASDVWSY GIVLWEVMSY GERPYWEMSN QDVIKAVDEG
   841  YRLPPPMDCP AALYQLMLDC WQKDRNNRPK FEQIVSILDK LIRNPGSLKI ITSAAARPSN
   901  LLLDQSNVDI TTFRTTGDWL NGVWTAHCKE IFTGVEYSSC DTIAKISTDD MKKVGVTVVG
   961  PQKKIISSIK ALETQSKNGP VPV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against EPHA3 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

30 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about EPHA3.

Disease | AllUniProt

Conditions EPHA3 is implicated in, by any mechanism.

• Colorectal cancer (CRC) MIM:114500

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)

0.53

gnomAD pLI

0

gnomAD missense Z

0.65

DepMap mean gene effect

-0.07

DepMap dependency class

selective

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

• axon guidance
• cell adhesion
• cell migration
• cellular response to retinoic acid
• ephrin receptor signaling pathway
• fasciculation of motor neuron axon
• fasciculation of sensory neuron axon
• negative regulation of endocytosis
• negative regulation of epithelial to mesenchymal transition
• peptidyl-tyrosine phosphorylation
• positive regulation of neuron projection development
• positive regulation of protein localization to plasma membrane
• regulation of actin cytoskeleton organization
• regulation of cell-cell adhesion
• regulation of epithelial to mesenchymal transition
• regulation of focal adhesion assembly
• regulation of GTPase activity
• regulation of microtubule cytoskeleton organization

Molecular functions

• ATP binding
• ephrin receptor activity
• GPI-linked ephrin receptor activity
• transmembrane-ephrin receptor activity

Cellular components

• actin cytoskeleton
• cytosol
• dendrite
• early endosome
• extracellular region
• nuclear membrane
• nucleoplasm
• plasma membrane

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
• Growth factor receptor cysteine-rich domain superfamily
• Protein kinase-like domain superfamily
• Tyrosine-protein kinase ephrin type A/B receptor-like
• 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)
• Tyrosine-protein kinase ephrin type A/B receptor-like
• Protein tyrosine and serine/threonine kinase
• Ephrin type-A receptor 2 transmembrane domain
• Ephrin cysteine rich domain
• Ephrin type-A receptor 3, ligand binding domain

KeywordsUniProt

• ATP-binding
• Cell adhesion
• Cell membrane
• Glycoprotein
• Kinase
• Membrane
• Nucleotide-binding
• Phosphoprotein
• Receptor
• Repeat
• Secreted
• Signal
• Transferase
• Transmembrane
• Transmembrane helix
• Tyrosine-protein kinase

InteractionsUniProt · HPA

Protein binding partners of EPHA3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NCK1
• PTPN1
• CRK
• EPHA2
• EPHA7