Human Gene EPHA3 (uc003dqy.3)
  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 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:89,156,674-89,531,284)mRNA (may differ from genome)Protein (983 aa)
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-  Comments and Description Text from UniProtKB
  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.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): EPHA3
CDC HuGE Published Literature: EPHA3
Positive Disease Associations: Cholesterol, HDL , Neuroblastoma , Triglycerides
Related Studies:
  1. 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.
  2. 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.
  3. 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.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: EPHA3
Diseases sorted by gene-association score: kummell's disease (12), beriberi (12), ariboflavinosis (9), myelophthisic anemia (7), pseudohypoaldosteronism, type i (7), lung large cell carcinoma (6), colorectal cancer (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 8.82 RPKM in Prostate
Total median expression: 80.00 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -78.44225-0.349 Picture PostScript Text
3' UTR -610.102632-0.232 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001090 - Ephrin_rcpt_lig-bd_dom
IPR003961 - Fibronectin_type3
IPR008979 - Galactose-bd-like
IPR013783 - Ig-like_fold
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR001660 - SAM
IPR013761 - SAM/pointed
IPR011510 - SAM_2
IPR001245 - Ser-Thr/Tyr_kinase_cat_dom
IPR011641 - Tyr-kin_ephrin_A/B_rcpt-like
IPR008266 - Tyr_kinase_AS
IPR020635 - Tyr_kinase_cat_dom
IPR016257 - Tyr_kinase_ephrin_rcpt
IPR001426 - Tyr_kinase_rcpt_V_CS

Pfam Domains:
PF00041 - Fibronectin type III domain
PF00069 - Protein kinase domain
PF00536 - SAM domain (Sterile alpha motif)
PF01404 - Ephrin receptor ligand binding domain
PF07647 - SAM domain (Sterile alpha motif)
PF07699 - Putative ephrin-receptor like
PF07714 - Protein tyrosine kinase
PF14575 - Ephrin type-A receptor 2 transmembrane domain

SCOP Domains:
47769 - SAM/Pointed domain
49265 - Fibronectin type III
49785 - Galactose-binding domain-like
56112 - Protein kinase-like (PK-like)
57184 - Growth factor receptor domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2GSF - X-ray MuPIT 2QO2 - X-ray MuPIT 2QO7 - X-ray MuPIT 2QO9 - X-ray MuPIT 2QOB - X-ray MuPIT 2QOC - X-ray MuPIT 2QOD - X-ray MuPIT 2QOF - X-ray MuPIT 2QOI - X-ray MuPIT 2QOK - X-ray MuPIT 2QOL - X-ray MuPIT 2QON - X-ray MuPIT 2QOO - X-ray MuPIT 2QOQ - X-ray MuPIT 3DZQ - X-ray MuPIT 3FXX - X-ray MuPIT 3FY2 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P29320
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005003 ephrin receptor activity
GO:0005004 GPI-linked ephrin receptor activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity

Biological Process:
GO:0006468 protein phosphorylation
GO:0007155 cell adhesion
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0010717 regulation of epithelial to mesenchymal transition
GO:0010976 positive regulation of neuron projection development
GO:0016310 phosphorylation
GO:0016477 cell migration
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0032956 regulation of actin cytoskeleton organization
GO:0043087 regulation of GTPase activity
GO:0045806 negative regulation of endocytosis
GO:0048013 ephrin receptor signaling pathway
GO:0051893 regulation of focal adhesion assembly
GO:0070507 regulation of microtubule cytoskeleton organization
GO:0071300 cellular response to retinoic acid
GO:0097155 fasciculation of sensory neuron axon
GO:0097156 fasciculation of motor neuron axon
GO:1903078 positive regulation of protein localization to plasma membrane

Cellular Component:
GO:0005576 extracellular region
GO:0005769 early endosome
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane


-  Descriptions from all associated GenBank mRNAs
  AF213459 - Homo sapiens ephrin receptor EPHA3 complete form (EPHA3) mRNA, complete cds.
BC063282 - Homo sapiens EPH receptor A3, mRNA (cDNA clone MGC:71556 IMAGE:30347891), complete cds.
M83941 - Human receptor tyrosine kinase (HEK) mRNA, complete cds.
AF213460 - Homo sapiens ephrin receptor EPHA3 secreted form (EPHA3) mRNA, complete cds.
BC026247 - Homo sapiens cDNA clone IMAGE:4720840, containing frame-shift errors.
AK291411 - Homo sapiens cDNA FLJ77258 complete cds, highly similar to Homo sapiens EPH receptor A3 (EPHA3), transcript variant 1, mRNA.
HM005377 - Homo sapiens clone HTL-T-64 testicular tissue protein Li 64 mRNA, complete cds.
AB384708 - Synthetic construct DNA, clone: pF1KB1569, Homo sapiens EPHA3 gene for ephrin type-A receptor 3 precursor, complete cds, without stop codon, in Flexi system.
KJ896774 - Synthetic construct Homo sapiens clone ccsbBroadEn_06168 EPHA3 gene, encodes complete protein.
JD198932 - Sequence 179956 from Patent EP1572962.
JD436158 - Sequence 417182 from Patent EP1572962.
JD226471 - Sequence 207495 from Patent EP1572962.
JD140444 - Sequence 121468 from Patent EP1572962.
JD271735 - Sequence 252759 from Patent EP1572962.
JD464712 - Sequence 445736 from Patent EP1572962.
HM437236 - Homo sapiens ephrin type-A receptor 3 variant (EPHA3) mRNA, partial cds.
AK024352 - Homo sapiens cDNA FLJ14290 fis, clone PLACE1006795.
JD526530 - Sequence 507554 from Patent EP1572962.
JD137390 - Sequence 118414 from Patent EP1572962.
JD433315 - Sequence 414339 from Patent EP1572962.
JD450644 - Sequence 431668 from Patent EP1572962.
JD288267 - Sequence 269291 from Patent EP1572962.
JD060987 - Sequence 42011 from Patent EP1572962.
JD049463 - Sequence 30487 from Patent EP1572962.
JD319071 - Sequence 300095 from Patent EP1572962.
JD427221 - Sequence 408245 from Patent EP1572962.
JD088709 - Sequence 69733 from Patent EP1572962.
CQ873837 - Sequence 256 from Patent WO2004076622.
DD413674 - Regulation of Mammalian Cells.
JD315594 - Sequence 296618 from Patent EP1572962.
JD431276 - Sequence 412300 from Patent EP1572962.
JD048630 - Sequence 29654 from Patent EP1572962.
JD307714 - Sequence 288738 from Patent EP1572962.
JD196732 - Sequence 177756 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04360 - Axon guidance

Reactome (by CSHL, EBI, and GO)

Protein P29320 (Reactome details) participates in the following event(s):

R-HSA-3928646 EPHAs bind EFNAs
R-HSA-3928597 EPH:EFN dimers tetramerise
R-HSA-2682334 EPH-Ephrin signaling
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
R-HSA-422475 Axon guidance
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: EPHA3_HUMAN, ETK, ETK1, HEK, NM_005233, NP_005224, P29320, Q9H2V3, Q9H2V4, TYRO4
UCSC ID: uc003dqy.3
RefSeq Accession: NM_005233
Protein: P29320 (aka EPHA3_HUMAN)
CCDS: CCDS2922.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_005233.5
exon count: 17CDS single in 3' UTR: no RNA size: 5837
ORF size: 2952CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6010.00frame shift in genome: no % Coverage: 99.52
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.