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MGP000962

UniProt Annotations

Entry Information

Gene Name	EPH receptor A3
Protein Entry	EPHA3_HUMAN
UniProt ID	P29320
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P29320-1; Sequence=Displayed; Name=2; IsoId=P29320-2; Sequence=VSP_002995, VSP_002996;
Catalytic Activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255\|PROSITE- ProRule:PRU10028}.
Disease	Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The gene represented in this entry may be involved in disease pathogenesis.
Function	Receptor tyrosine kinase which binds promiscuously 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 for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269\|PubMed:11870224}.
Ptm	Autophosphorylates upon activation by EFNA5. Phosphorylation on Tyr-602 mediates interaction with NCK1. Dephosphorylated by PTPN1. {ECO:0000269\|PubMed:11870224, ECO:0000269\|PubMed:18547520, ECO:0000269\|PubMed:21135139}.
Similarity	Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. {ECO:0000255\|PROSITE- ProRule:PRU00159}.
Similarity	Contains 1 Eph LBD (Eph ligand-binding) domain. {ECO:0000255\|PROSITE-ProRule:PRU00883}.
Similarity	Contains 1 protein kinase domain. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Similarity	Contains 1 SAM (sterile alpha motif) domain. {ECO:0000255\|PROSITE-ProRule:PRU00184}.
Similarity	Contains 2 fibronectin type-III domains. {ECO:0000255\|PROSITE-ProRule:PRU00316}.
Subcellular Location	Isoform 1: Cell membrane; Single-pass type I membrane protein.
Subcellular Location	Isoform 2: Secreted.
Subunit	Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function. Interacts with NCK1 (via SH2 domain); mediates EFNA5-EPHA3 signaling (By similarity). Interacts (phosphorylated) with PTPN1; dephosphorylates EPHA3 and may regulate its trafficking and function. Interacts (phosphorylated) with CRK; mediates EFNA5- EPHA3 signaling through RHOA GTPase activation. {ECO:0000250, ECO:0000269\|PubMed:11870224, ECO:0000269\|PubMed:14660665, ECO:0000269\|PubMed:16239146, ECO:0000269\|PubMed:18547520, ECO:0000269\|PubMed:21135139}.
Tissue Specificity	Widely expressed. Highest level in placenta.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/EPHA3ID40463ch3p11.html";