Description: Homo sapiens EPH receptor A3 (EPHA3), transcript variant 1, mRNA. RefSeq Summary (NM_005233): 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]. Transcript (Including UTRs) Position: hg19 chr3:89,156,674-89,531,284 Size: 374,611 Total Exon Count: 17 Strand: + Coding Region Position: hg19 chr3:89,156,899-89,528,652 Size: 371,754 Coding Exon Count: 17
ID:EPHA3_HUMAN DESCRIPTION: RecName: Full=Ephrin type-A receptor 3; EC=2.7.10.1; AltName: Full=EPH-like kinase 4; Short=EK4; Short=hEK4; AltName: Full=HEK; Short=Human embryo kinase; AltName: Full=Tyrosine-protein kinase TYRO4; AltName: Full=Tyrosine-protein kinase receptor ETK1; Short=Eph-like tyrosine kinase 1; Flags: Precursor; 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. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. 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. SUBCELLULAR LOCATION: Isoform 1: Cell membrane; Single-pass type I membrane protein. SUBCELLULAR LOCATION: Isoform 2: Secreted. TISSUE SPECIFICITY: Widely expressed. Highest level in placenta. PTM: Autophosphorylates upon activation by EFNA5. Phosphorylation on Tyr-602 mediates interaction with NCK1. Dephosphorylated by PTPN1. DISEASE: Defects in EPHA3 may be a cause of colorectal cancer (CRC) [MIM:114500]. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily. SIMILARITY: Contains 1 Eph LBD (Eph ligand-binding) domain. SIMILARITY: Contains 2 fibronectin type-III domains. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SAM (sterile alpha motif) domain.
Cholesterol, HDL Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics.
[PubMed 17903299]
Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
Neuroblastoma John M Maris et al. The New England journal of medicine 2008, Chromosome 6p22 locus associated with clinically aggressive neuroblastoma., The New England journal of medicine.
[PubMed 18463370]
A common genetic variation at chromosome band 6p22 is associated with susceptibility to neuroblastoma.
Neuroblastoma John M Maris et al. The New England journal of medicine 2008, Chromosome 6p22 locus associated with clinically aggressive neuroblastoma., The New England journal of medicine.
[PubMed 18463370]
A common genetic variation at chromosome band 6p22 is associated with susceptibility to neuroblastoma.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P29320
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.