EPHA2
entrez
1969
canonical
uniprot
P29317
canonical
ensembl
ENSG00000142627
resolver
ensp
ENSP00000351209
resolver
genesymbol
EPHA2
resolver
genesymbol_syn
ECK
resolver
hgnc
HGNC:3386
resolver
uniprot
B5A968
resolver
uniprot
Q8N3Z2
resolver
uniprot_entry
EPHA2_HUMAN
resolver
uniprot_sec
B5A968
resolver
uniprot_sec
Q8N3Z2
resolver
amino_acid_sequence
MELQAARACFALLWGCALAAAAAAQGKEVVLLDFAAAGGELGWLTHPYGKGWDLMQNIMNDMPIYMYSVCNVMSGDQDNWLRTNWVYRGEAERIFIELKFTVRDCNSFPGGASSCKETFNLYYAESDLDYGTNFQKRLFTKIDTIAPDEITVSSDFEARHVKLNVEERSVGPLTRKGFYLAFQDIGACVALLSVRVYYKKCPELLQGLAHFPETIAGSDAPSLATVAGTCVDHAVVPPGGEEPRMHCAVDGEWLVPIGQCLCQAGYEKVEDACQACSPGFFKFEASESPCLECPEHTLPSPEGATSCECEEGFFRAPQDPASMPCTRPPSAPHYLTAVGMGAKVELRWTPPQDSGGREDIVYSVTCEQCWPESGECGPCEASVRYSEPPHGLTRTSVTVSDLEPHMNYTFTVEARNGVSGLVTSRSFRTASVSINQTEPPKVRLEGRSTTSLSVSWSIPPPQQSRVWKYEVTYRKKGDSNSYNVRRTEGFSVTLDDLAPDTTYLVQVQALTQEGQGAGSKVHEFQTLSPEGSGNLAVIGGVAVGVVLLLVLAGVGFFIHRRRKNQRARQSPEDVYFSKSEQLKPLKTYVDPHTYEDPNQAVLKFTTEIHPSCVTRQKVIGAGEFGEVYKGMLKTSSGKKEVPVAIKTLKAGYTEKQRVDFLGEAGIMGQFSHHNIIRLEGVISKYKPMMIITEYMENGALDKFLREKDGEFSVLQLVGMLRGIAAGMKYLANMNYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDPEATYTTSGGKIPIRWTAPEAISYRKFTSASDVWSFGIVMWEVMTYGERPYWELSNHEVMKAINDGFRLPTPMDCPSAIYQLMMQCWQQERARRPKFADIVSILDKLIRAPDSLKTLADFDPRVSIRLPSTSGSEGVPFRTVSEWLESIKMQQYTEHFMAAGYTAIEKVVQMTNDDIKRIGVRLPGHQKRIAYSLLGLKDQVNTVGIPI
uniprot
proteins
disease_involvement
DISEASE: Cataract 6, multiple types (CTRCT6) [MIM:116600]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT6 includes posterior polar and age-related cortical cataracts, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens. Age-related cortical cataract is a developmental punctate opacity restricted to the cortex. The cataract is white or cerulean, increases in number with age, but rarely affects vision. {ECO:0000269|PubMed:19005574, ECO:0000269|PubMed:19306328, ECO:0000269|PubMed:19649315, ECO:0000269|PubMed:22570727}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=Overexpressed in several cancer types and promotes malignancy. {ECO:0000269|PubMed:19573808}.
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A 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. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand-independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:18339848, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20679435, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. Mediates HCV entry by promoting the formation of the CD81-CLDN1 receptor complexes that are essential for HCV entry and by enhancing membrane fusion of cells expressing HCV envelope glycoproteins. {ECO:0000269|PubMed:21516087}.; FUNCTION: Acts as a receptor for human cytomegalovirus (HCMV) to mediate viral entry and fusion in glioblastoma cells. {ECO:0000269|PubMed:37146061}.
uniprot
proteins
mass_dalton
108266
uniprot
proteins
mutagenesis
MUTAGEN 103; /note="R->E: Significantly reduced response to EFNA1."; /evidence="ECO:0000269|PubMed:19525919"; MUTAGEN 646; /note="K->M: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:16236711"; MUTAGEN 739; /note="D->N: Increases serum-induced chemotaxis. Loss of EFNA1-dependent regulation of cell migration."; /evidence="ECO:0000269|PubMed:19573808"; MUTAGEN 897; /note="S->A,D: Loss of serum-induced phosphorylation by PKB. Loss of serum-induced chemotaxis."; /evidence="ECO:0000269|PubMed:19573808
uniprot
proteins
post_translational_modification
PTM: Autophosphorylates. Phosphorylated on tyrosine upon binding and activation by EFNA1. Phosphorylated residues Tyr-588 and Tyr-594 are required for binding VAV2 and VAV3 while phosphorylated residues Tyr-735 and Tyr-930 are required for binding PI3-kinase p85 subunit (PIK3R1, PIK3R2 or PIK3R3). These phosphorylated residues are critical for recruitment of VAV2 and VAV3 and PI3-kinase p85 subunit which transduce downstream signaling to activate RAC1 GTPase and cell migration. Dephosphorylation of Tyr-930 by PTPRF prevents the interaction of EPHA2 with NCK1. Phosphorylated at Ser-897 by PKB; serum-induced phosphorylation which targets EPHA2 to the cell leading edge and stimulates cell migration. Phosphorylation by PKB is inhibited by EFNA1-activated EPHA2 which regulates PKB activity via a reciprocal regulatory loop. Phosphorylated at Ser-897 in response to TNF by RPS6KA1 and RPS6KA3; RPS6KA-EPHA2 signaling pathway controls cell migration (PubMed:26158630). Phosphorylated at Ser-897 by PKA; blocks cell retraction induced by EPHA2 kinase activity (PubMed:27385333). Dephosphorylated by ACP1. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:18794797, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:27385333}.; PTM: Ubiquitinated by CHIP/STUB1. Ubiquitination is regulated by the HSP90 chaperone and regulates the receptor stability and activity through proteasomal degradation. ANKS1A prevents ubiquitination and degradation (By similarity). {ECO:0000250}.
uniprot
proteins
protein_family
Ephrin receptor subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10655584
uniprot
proteins
pubmed
11280802
uniprot
proteins
pubmed
12167657
uniprot
proteins
pubmed
12467573
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16236711
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17135240
uniprot
proteins
pubmed
17332925
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18339848
uniprot
proteins
pubmed
18593464
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18794797
uniprot
proteins
pubmed
19005574
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19306328
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19525919
uniprot
proteins
pubmed
19567782
uniprot
proteins
pubmed
19573808
uniprot
proteins
pubmed
19649315
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20223987
uniprot
proteins
pubmed
20505120
uniprot
proteins
pubmed
20679435
uniprot
proteins
pubmed
20861311
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21516087
uniprot
proteins
pubmed
2174105
uniprot
proteins
pubmed
22332920
uniprot
proteins
pubmed
22570727
uniprot
proteins
pubmed
22635007
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23358419
uniprot
proteins
pubmed
23936024
uniprot
proteins
pubmed
26158630
uniprot
proteins
pubmed
27385333
uniprot
proteins
pubmed
29292383
uniprot
proteins
pubmed
29292384
uniprot
proteins
pubmed
34067457
uniprot
proteins
pubmed
37146061
uniprot
proteins
pubmed
9267020
uniprot
proteins
sequence_length
976
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18794797, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20223987, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:34067457}; Single-pass type I membrane protein {ECO:0000255}. Cell projection, ruffle membrane {ECO:0000269|PubMed:19573808}; Single-pass type I membrane protein {ECO:0000255}. Cell projection, lamellipodium membrane {ECO:0000269|PubMed:19573808}; Single-pass type I membrane protein {ECO:0000255}. Cell junction, focal adhesion {ECO:0000269|PubMed:10655584}. Note=Present at regions of cell-cell contacts but also at the leading edge of migrating cells (PubMed:19573808, PubMed:20861311). Relocates from the plasma membrane to the cytoplasmic and perinuclear regions in cancer cells (PubMed:18794797). {ECO:0000269|PubMed:18794797, ECO:0000269|PubMed:19573808, ECO:0000269|PubMed:20861311, ECO:0000269|PubMed:26158630}.
uniprot
proteins
transmembrane_region
TRANSMEM 538..558; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins