Human Gene EPHA1 (uc003wcz.3) Description and Page Index
  Description: Homo sapiens EPH receptor A1 (EPHA1), mRNA.
RefSeq Summary (NM_005232): 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 is expressed in some human cancer cell lines and has been implicated in carcinogenesis. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: AK290351.1, M18391.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000275815.4/ ENSP00000275815.3 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr7:143,088,205-143,105,985 Size: 17,781 Total Exon Count: 18 Strand: -
Coding Region
   Position: hg19 chr7:143,088,550-143,105,898 Size: 17,349 Coding Exon Count: 18 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr7:143,088,205-143,105,985)mRNA (may differ from genome)Protein (976 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Ephrin type-A receptor 1; Short=hEpha1; EC=; AltName: Full=EPH tyrosine kinase; AltName: Full=EPH tyrosine kinase 1; AltName: Full=Erythropoietin-producing hepatoma receptor; AltName: Full=Tyrosine-protein kinase receptor EPH; Flags: Precursor;
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. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Plays also a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis.
CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SUBUNIT: Homodimer. Forms a signaling complex with LCK; PTK2B/PYK2 and PI3-kinase upon activation by EFNA1; regulates T-lymphocytes migration. Interacts (via SAM domain) with ILK (via ANK repeats); stimulated by EFNA1 but independent of the kinase activity of EPHA1. Interacts (kinase activity-dependent) with PTK2/FAK1.
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein.
TISSUE SPECIFICITY: Overexpressed in several carcinomas.
PTM: Phosphorylated. Autophosphorylation is stimulated by its ligand EFNA1.
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.
SEQUENCE CAUTION: Sequence=AAA36747.1; Type=Frameshift; Positions=582, 595, 601;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): EPHA1
CDC HuGE Published Literature: EPHA1
Positive Disease Associations: Alzheimer Disease
Related Studies:
  1. Alzheimer Disease
    Adam C Naj et al. Nature genetics 2011, Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease., Nature genetics. [PubMed 21460841]

-  MalaCards Disease Associations
  MalaCards Gene Search: EPHA1
Diseases sorted by gene-association score: placenta praevia (11), craniofrontonasal dysplasia (10), good syndrome (6), rh isoimmunization (5), uterine disease (4), placenta disease (4)

-  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: 42.83 RPKM in Esophagus - Mucosa
Total median expression: 164.83 RPKM

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

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -30.8087-0.354 Picture PostScript Text
3' UTR -121.80345-0.353 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
IPR009030 - Growth_fac_rcpt
IPR013783 - Ig-like_fold
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR001660 - SAM
IPR013761 - SAM/pointed
IPR021129 - SAM_type1
IPR001245 - Ser-Thr/Tyr_kinase_cat_dom
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)
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)

Protein Data Bank (PDB) 3-D Structure
MuPIT help



- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3KKA - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P21709
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 orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  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:0005005 transmembrane-ephrin receptor activity
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0019901 protein kinase binding

Biological Process:
GO:0001525 angiogenesis
GO:0001954 positive regulation of cell-matrix adhesion
GO:0006468 protein phosphorylation
GO:0006469 negative regulation of protein kinase activity
GO:0007155 cell adhesion
GO:0007166 cell surface receptor signaling pathway
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0008284 positive regulation of cell proliferation
GO:0016310 phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0030335 positive regulation of cell migration
GO:0030336 negative regulation of cell migration
GO:0034446 substrate adhesion-dependent cell spreading
GO:0035019 somatic stem cell population maintenance
GO:0043087 regulation of GTPase activity
GO:0045766 positive regulation of angiogenesis
GO:0046777 protein autophosphorylation
GO:0048013 ephrin receptor signaling pathway
GO:0051496 positive regulation of stress fiber assembly
GO:0090630 activation of GTPase activity

Cellular Component:
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
  Z27409 - H.sapiens mRNA for receptor tyrosine kinase eph (partial).
M18391 - Human tyrosine kinase receptor (eph) mRNA, complete cds.
JD341263 - Sequence 322287 from Patent EP1572962.
JD123516 - Sequence 104540 from Patent EP1572962.
AK290351 - Homo sapiens cDNA FLJ76013 complete cds, highly similar to Homo sapiens EPH receptor A1 (EPHA1), mRNA.
JD381143 - Sequence 362167 from Patent EP1572962.
JD216228 - Sequence 197252 from Patent EP1572962.
JD534007 - Sequence 515031 from Patent EP1572962.
JD220170 - Sequence 201194 from Patent EP1572962.
BC130291 - Homo sapiens EPH receptor A1, mRNA (cDNA clone MGC:163163 IMAGE:40146322), complete cds.
BC144156 - Homo sapiens cDNA clone IMAGE:9052676.
AK313263 - Homo sapiens cDNA, FLJ93773.
KJ896773 - Synthetic construct Homo sapiens clone ccsbBroadEn_06167 EPHA1 gene, encodes complete protein.
EU826605 - Homo sapiens soluble EPHA1 variant 2 (EPHA1) mRNA, complete cds, alternatively spliced.
EU826604 - Homo sapiens soluble EPHA1 variant 1 (EPHA1) mRNA, complete cds, alternatively spliced.
JD142289 - Sequence 123313 from Patent EP1572962.

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

Reactome (by CSHL, EBI, and GO)

Protein P21709 (Reactome details) participates in the following event(s):

R-HSA-3928646 EPHAs bind EFNAs
R-HSA-3928597 EPH:EFN dimers tetramerise
R-HSA-2892247 POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
R-HSA-2682334 EPH-Ephrin signaling
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
R-HSA-452723 Transcriptional regulation of pluripotent stem cells
R-HSA-422475 Axon guidance
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: A1L3V3, EPH, EPHA1_HUMAN, EPHT, EPHT1, NM_005232, NP_005223, P21709, Q15405
UCSC ID: uc003wcz.3
RefSeq Accession: NM_005232
Protein: P21709 (aka EPHA1_HUMAN)
CCDS: CCDS5884.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_005232.4
exon count: 18CDS single in 3' UTR: no RNA size: 3369
ORF size: 2931CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6062.00frame shift in genome: no % Coverage: 99.82
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.