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Aliases for EPHA4 Gene

Aliases for EPHA4 Gene

  • EPH Receptor A4 2 3
  • 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
  • Ephrin Type-A Receptor 4 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 staphyloenterotoxemia. Among its related pathways are GPCR Pathway and Akt Signaling. GO annotations related to this gene include protein kinase activity and transmembrane-ephrin receptor activity. An important paralog of this gene is EPHB3.

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.

Gene Wiki entry for EPHA4 Gene

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

Genomics for EPHA4 Gene

Regulatory Elements for EPHA4 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for EPHA4 Gene

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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 Lys735
  • Glycosylation at Asn235, Asn340, Asn408, and Asn545
  • Modification sites at PhosphoSitePlus

Antibody Products

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

Domains for EPHA4 Gene

Gene Families for EPHA4 Gene

HGNC:
  • EPH :EPH receptors
  • FN3 :Fibronectin type III domain containing
  • SAMD :Sterile alpha motif (SAM) domain containing
IUPHAR :

Suggested Antigen Peptide Sequences for EPHA4 Gene

Graphical View of Domain Structure for InterPro Entry

P54764

UniProtKB/Swiss-Prot:

EPHA4_HUMAN :
  • P54764
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:0004672 protein kinase activity IDA 12775584
GO:0004713 protein tyrosine kinase activity --
GO:0005003 ephrin receptor activity --
GO:0005004 GPI-linked ephrin receptor activity ISS --
GO:0005005 transmembrane-ephrin receptor activity ISS --
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

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for EPHA4

Clone Products

  • Addgene plasmids for EPHA4

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targeting 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:0005737 cytoplasm ISS --
GO:0005741 mitochondrial outer membrane IEA --
GO:0005783 endoplasmic reticulum IEA --
GO:0005794 Golgi apparatus IEA --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with EPHA4: view

Pathways for EPHA4 Gene

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

Pathways by source for EPHA4 Gene

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

Gene Ontology (GO) - Biological Process for EPHA4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation --
GO:0007155 cell adhesion IEA --
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway --
GO:0007411 axon guidance TAS --
GO:0007628 adult walking behavior IEA --
genes like me logo Genes that share ontologies with EPHA4: view

Compounds for EPHA4 Gene

(2) HMDB Compounds for EPHA4 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(1) Novoseek inferred chemical compound relationships for EPHA4 Gene

Compound -log(P) Hits PubMed IDs
tyrosine 63.2 15
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:

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for EPHA4

Clone Products

  • Addgene plasmids for EPHA4

Primer 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) (4.8).

Integrated Proteomics: protein expression 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 expressions with EPHA4: view

In Situ Assay Products

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 35
  • 92.99 (n)
  • 99.03 (a)
EPHA4 36
  • 99 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Epha4 35
  • 90.67 (n)
  • 98.58 (a)
Epha4 16
Epha4 36
  • 99 (a)
OneToOne
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 35
  • 83.47 (n)
  • 94.22 (a)
EPHA4 36
  • 94 (a)
OneToOne
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 35
  • 74.42 (n)
  • 82.42 (a)
epha4a 36
  • 79 (a)
OneToMany
epha4l 36
  • 74 (a)
OneToMany
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 MAF
rs8508 -- 221,418,239(-) CCAAA(A/C)TTTGA utr-variant-3-prime
rs9758 -- 221,418,280(-) CTGAA(A/T)AAGAA utr-variant-3-prime
rs919502 -- 221,460,611(-) GCAAA(A/G)CCCAG intron-variant
rs919503 -- 221,460,419(-) ACAAT(A/G)CTTTT intron-variant
rs934283 -- 221,490,307(+) CCAAG(A/G)CAAGA 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

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

MalaCards: The human disease database. (1) Diseases for EPHA4 Gene including...

Search for EPHA4 Gene in MalaCards »

(2) University of Copenhagen DISEASES for EPHA4 Gene

(1) Novoseek inferred disease relationships for EPHA4 Gene

Disease -log(P) Hits PubMed IDs
tumors 0 2

Relevant External Links for EPHA4

Genetic Association Database (GAD)
EPHA4
Human Genome Epidemiology (HuGE) Navigator
EPHA4
genes like me logo Genes that share disorders with EPHA4: view

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

Publications for EPHA4 Gene

  1. cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases. (PMID: 7898931) Fox G.M. … Welcher A.A. (Oncogene 1995) 3 4 23
  2. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. (PMID: 9267020) (Cell 1997) 2 3 4
  3. Aberrant expression of the tyrosine kinase receptor EphA4 and the transcription factor twist in SAczary syndrome identified by gene expression analysis. (PMID: 15313894) van Doorn R. … Tensen C.P. (Cancer Res. 2004) 3 23
  4. 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
  5. Crystal structure and NMR binding reveal that two small molecule antagonists target the high affinity ephrin-binding channel of the EphA4 receptor. (PMID: 18708347) Qin H. … Song J. (J. Biol. Chem. 2008) 4 23

Products for EPHA4 Gene

  • Addgene plasmids for EPHA4

Sources for EPHA4 Gene

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