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Aliases for EPHA4 Gene

Aliases for EPHA4 Gene

  • EPH Receptor A4 2 3 5
  • Tyrosine-Protein Kinase Receptor SEK 3 4
  • Tyrosine-Protein Kinase TYRO1 3 4
  • EPH-Like Kinase 8 3 4
  • EC 2.7.10.1 4 63
  • TYRO1 3 4
  • HEK8 3 4
  • EK8 3 4
  • SEK 3 4
  • Receptor Protein-Tyrosine Kinase HEK8 3
  • TYRO1 Protein Tyrosine Kinase 3
  • EC 2.7.10 63
  • EphA4 2

External Ids for EPHA4 Gene

Previous HGNC Symbols for EPHA4 Gene

  • TYRO1

Previous GeneCards Identifiers for EPHA4 Gene

  • GC02M220313
  • GC02M221011
  • GC02M222248
  • GC02M222492
  • GC02M222108
  • GC02M221990
  • GC02M214137

Summaries for EPHA4 Gene

Entrez Gene Summary for EPHA4 Gene

  • 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

GeneCards Summary for EPHA4 Gene

EPHA4 (EPH Receptor A4) is a Protein Coding gene. Diseases associated with EPHA4 include spinal cord injury. Among its related pathways are EphB-EphrinB Signaling and Developmental Biology. GO annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is EPHA3.

UniProtKB/Swiss-Prot for EPHA4 Gene

  • Receptor tyrosine kinase which binds 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, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at Tyr-15 which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium.

Tocris Summary for EPHA4 Gene

Gene Wiki entry for EPHA4 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EPHA4 Gene

Genomics for EPHA4 Gene

Regulatory Elements for EPHA4 Gene

Promoters for EPHA4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around EPHA4 on UCSC Golden Path with GeneCards custom track

Genomic Location for EPHA4 Gene

Chromosome:
2
Start:
221,418,027 bp from pter
End:
221,574,202 bp from pter
Size:
156,176 bases
Orientation:
Minus strand

Genomic View for EPHA4 Gene

Genes around EPHA4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EPHA4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EPHA4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EPHA4 Gene

Proteins for EPHA4 Gene

  • Protein details for EPHA4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P54764-EPHA4_HUMAN
    Recommended name:
    Ephrin type-A receptor 4
    Protein Accession:
    P54764
    Secondary Accessions:
    • A8K2P1
    • B2R601
    • B7Z6Q8
    • Q2M380

    Protein attributes for EPHA4 Gene

    Size:
    986 amino acids
    Molecular mass:
    109860 Da
    Quaternary structure:
    • 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. Interacts (phosphorylated at position Tyr-602) with FYN. Interacts with CDK5, CDK5R1 and NGEF; upon activation by EFNA1 induces NGEF phosphorylation by the kinase CDK5. Interacts with CHN1; effector of EPHA4 in axon guidance linking EPHA4 activation to RAC1 regulation (By similarity). Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases.

    Three dimensional structures from OCA and Proteopedia for EPHA4 Gene

    Alternative splice isoforms for EPHA4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EPHA4 Gene

Proteomics data for EPHA4 Gene at MOPED

Post-translational modifications for EPHA4 Gene

  • Ubiquitination at Lys 735
  • Glycosylation at Asn 235, Asn 340, Asn 408, and Asn 545
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for EPHA4 (EphA4)

Domains & Families for EPHA4 Gene

Suggested Antigen Peptide Sequences for EPHA4 Gene

Graphical View of Domain Structure for InterPro Entry

P54764

UniProtKB/Swiss-Prot:

EPHA4_HUMAN :
  • The protein kinase domain mediates interaction with NGEF.
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.
Domain:
  • The protein kinase domain mediates interaction with NGEF.
  • Contains 1 Eph LBD (Eph ligand-binding) domain.
  • Contains 2 fibronectin type-III domains.
  • Contains 1 protein kinase domain.
  • Contains 1 SAM (sterile alpha motif) domain.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.
genes like me logo Genes that share domains with EPHA4: view

Function for EPHA4 Gene

Molecular function for EPHA4 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot Function:
Receptor tyrosine kinase which binds 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, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at Tyr-15 which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium.

Enzyme Numbers (IUBMB) for EPHA4 Gene

Gene Ontology (GO) - Molecular Function for EPHA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004713 protein tyrosine kinase activity IEA --
genes like me logo Genes that share ontologies with EPHA4: view
genes like me logo Genes that share phenotypes with EPHA4: view

Animal Models for EPHA4 Gene

MGI Knock Outs for EPHA4:

Animal Model Products

miRNA for EPHA4 Gene

miRTarBase miRNAs that target EPHA4

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for EPHA4 Gene

Localization for EPHA4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EPHA4 Gene

Cell membrane; Single-pass type I membrane protein. Cell projection, axon. Cell projection, dendrite. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density. Early endosome. Note=Clustered upon activation and targeted to early endosome. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for EPHA4 Gene COMPARTMENTS Subcellular localization image for EPHA4 gene
Compartment Confidence
plasma membrane 5
endosome 4
cytoskeleton 2
endoplasmic reticulum 2
golgi apparatus 2
mitochondrion 2
extracellular 1
nucleus 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for EPHA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IEA,TAS --
GO:0005887 integral component of plasma membrane IEA,ISS --
GO:0009986 cell surface IEA --
GO:0014069 postsynaptic density IEA --
GO:0030054 cell junction IEA --
genes like me logo Genes that share ontologies with EPHA4: view

Pathways & Interactions for EPHA4 Gene

genes like me logo Genes that share pathways with EPHA4: view

SIGNOR curated interactions for EPHA4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for EPHA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA --
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway IEA --
GO:0007411 axon guidance IEA --
GO:0007628 adult walking behavior IEA --
GO:0046777 protein autophosphorylation IDA 12775584
genes like me logo Genes that share ontologies with EPHA4: view

Drugs & Compounds for EPHA4 Gene

(2) Drugs for EPHA4 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0

(3) Additional Compounds for EPHA4 Gene - From: HMDB and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
KYL
676657-00-4
NVP BHG 712
940310-85-0
genes like me logo Genes that share compounds with EPHA4: view

Transcripts for EPHA4 Gene

Unigene Clusters for EPHA4 Gene

EPH receptor A4:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for EPHA4 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b · 5c ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b · 10c · 10d ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17a · 17b ^ 18 ^
SP1: - - - -
SP2: - - - -
SP3: - -
SP4: -
SP5:
SP6: - - - - - - - -
SP7:
SP8:
SP9:
SP10:

ExUns: 19 ^ 20a · 20b ^ 21a · 21b ^ 22 ^ 23 ^ 24
SP1: -
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10: -

Relevant External Links for EPHA4 Gene

GeneLoc Exon Structure for
EPHA4
ECgene alternative splicing isoforms for
EPHA4

Expression for EPHA4 Gene

mRNA expression in normal human tissues for EPHA4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for EPHA4 Gene

This gene is overexpressed in Brain - Frontal Cortex (BA9) (x4.8).

Protein differential expression in normal tissues from HIPED for EPHA4 Gene

This gene is overexpressed in Cerebrospinal fluid (41.6), Frontal cortex (11.0), and Serum (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for EPHA4 Gene



SOURCE GeneReport for Unigene cluster for EPHA4 Gene Hs.371218

mRNA Expression by UniProt/SwissProt for EPHA4 Gene

P54764-EPHA4_HUMAN
Tissue specificity: Ubiquitous.
genes like me logo Genes that share expression patterns with EPHA4: view

Primer Products

In Situ Assay Products

No data available for Protein tissue co-expression partners for EPHA4 Gene

Orthologs for EPHA4 Gene

This gene was present in the common ancestor of animals.

Orthologs for EPHA4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia EPHA4 35
  • 99.66 (n)
  • 100 (a)
EPHA4 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia EPHA4 36
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia EPHA4 36
  • 99 (a)
OneToOne
EPHA4 35
  • 92.99 (n)
  • 99.03 (a)
mouse
(Mus musculus)
Mammalia Epha4 36
  • 99 (a)
OneToOne
Epha4 16
Epha4 35
  • 90.67 (n)
  • 98.58 (a)
oppossum
(Monodelphis domestica)
Mammalia EPHA4 36
  • 96 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia EPHA4 36
  • 96 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Epha4 35
  • 89.82 (n)
  • 98.58 (a)
chicken
(Gallus gallus)
Aves EPHA4 36
  • 94 (a)
OneToOne
EPHA4 35
  • 83.47 (n)
  • 94.22 (a)
lizard
(Anolis carolinensis)
Reptilia EPHA4 36
  • 92 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia MGC53038 35
tropical clawed frog
(Silurana tropicalis)
Amphibia epha4 35
  • 78.56 (n)
  • 89.63 (a)
zebrafish
(Danio rerio)
Actinopterygii ek1 36
  • 64 (a)
OneToMany
epha4a 36
  • 79 (a)
OneToMany
epha4l 36
  • 74 (a)
OneToMany
epha4a 35
  • 74.42 (n)
  • 82.42 (a)
rtk4 35
fruit fly
(Drosophila melanogaster)
Insecta Eph 37
  • 41 (a)
worm
(Caenorhabditis elegans)
Secernentea vab-1 35
  • 49.02 (n)
  • 40.34 (a)
Species with no ortholog for EPHA4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for EPHA4 Gene

ENSEMBL:
Gene Tree for EPHA4 (if available)
TreeFam:
Gene Tree for EPHA4 (if available)

Paralogs for EPHA4 Gene

Paralogs for EPHA4 Gene

genes like me logo Genes that share paralogs with EPHA4: view

Variants for EPHA4 Gene

Sequence variations from dbSNP and Humsavar for EPHA4 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs952162 -- 221,548,331(+) TGCAC(C/T)CCAGC intron-variant
rs957465 -- 221,418,794(-) TCAGG(A/G)TCTGG utr-variant-3-prime
rs957466 -- 221,418,784(-) GGTCT(A/G)AGCCC utr-variant-3-prime
rs958165 -- 221,540,740(-) ATAAA(A/G)GGGAG intron-variant
rs962430 -- 221,447,682(-) TAGGG(A/G)AGGAG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for EPHA4 Gene

Variant ID Type Subtype PubMed ID
nsv875891 CNV Gain 21882294
esv2669891 CNV Deletion 23128226
nsv3174 CNV Insertion 18451855
essv11476 CNV CNV 17122850
dgv1289e1 CNV Complex 17122850
nsv428407 CNV Loss 18775914
esv2676923 CNV Deletion 23128226
nsv818114 CNV Loss 17921354
esv2721514 CNV Deletion 23290073
esv2657184 CNV Deletion 23128226
nsv526093 CNV Loss 19592680

Variation tolerance for EPHA4 Gene

Residual Variation Intolerance Score: 2.96% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.68; 32.13% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for EPHA4 Gene

HapMap Linkage Disequilibrium report
EPHA4
Human Gene Mutation Database (HGMD)
EPHA4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EPHA4 Gene

Disorders for EPHA4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for EPHA4 Gene - From: GeneCards

Disorder Aliases PubMed IDs
spinal cord injury
  • spinal cord injuries
- elite association - COSMIC cancer census association via MalaCards
Search EPHA4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for EPHA4

Genetic Association Database (GAD)
EPHA4
Human Genome Epidemiology (HuGE) Navigator
EPHA4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
EPHA4
genes like me logo Genes that share disorders with EPHA4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for EPHA4 Gene

Publications for EPHA4 Gene

  1. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. (PMID: 9267020) (Cell 1997) 2 3 4 67
  2. EphA4 promotes cell proliferation and migration through a novel EphA4-FGFR1 signaling pathway in the human glioma U251 cell line. (PMID: 18790757) Fukai J. … Itakura T. (Mol. Cancer Ther. 2008) 3 23
  3. Overexpression of EphA4 gene and reduced expression of EphB2 gene correlates with liver metastasis in colorectal cancer. (PMID: 18695888) Oshima T. … Imada T. (Int. J. Oncol. 2008) 3 23
  4. Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers. (PMID: 18837080) Oki M. … Shinomura Y. (World J. Gastroenterol. 2008) 3 23
  5. EphA4 receptor, overexpressed in pancreatic ductal adenocarcinoma, promotes cancer cell growth. (PMID: 16965393) Iiizumi M. … Nakagawa H. (Cancer Sci. 2006) 3 23

Products for EPHA4 Gene

Sources for EPHA4 Gene

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