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EPHA4 Gene

protein-coding   GIFtS: 71
GCID: GC02M222248

EPH Receptor A4

(Previous name: EphA4)
(Previous symbol: TYRO1)
  See EPHA4-related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
EPH Receptor A41 2     EC 2.7.10.13 8
TYRO11 2 3     EphA41
Tyrosine-Protein Kinase Receptor SEK2 3     Ephrin Type-A Receptor 42
Tyrosine-Protein Kinase TYRO12 3     Receptor Protein-Tyrosine Kinase HEK82
EK82 3     TYRO1 Protein Tyrosine Kinase2
HEK82 3     hEK83
SEK2 3     EC 2.7.108
EPH-Like Kinase 82 3     

External Ids:    HGNC: 33881   Entrez Gene: 20432   Ensembl: ENSG000001161067   OMIM: 6021885   UniProtKB: P547643   

Export aliases for EPHA4 gene to outside databases

Previous GC identifers: GC02M220313 GC02M221011 GC02M222492 GC02M222108 GC02M221990 GC02M214137


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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. (provided
by RefSeq, Jul 2008)

GeneCards Summary for EPHA4 Gene:
EPHA4 (EPH receptor A4) is a protein-coding gene. Diseases associated with EPHA4 include staphyloenterotoxemia. GO annotations related to this gene include transmembrane-ephrin receptor activity and protein kinase activity. An important paralog of this gene is EPHB1.

UniProtKB/Swiss-Prot: EPHA4_HUMAN, P54764
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. Beside 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 (EPH receptor A4) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000002.11  NT_005403.18  NC_018913.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the EPHA4 gene promoter:
         Nkx3-1   Sox5   Nkx3-1 v4   STAT1   Nkx3-1 v1   Nkx3-1 v2   FOXC1   STAT3   Nkx3-1 v3   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidEPHA4 promoter sequence
   Search Chromatin IP Primers for EPHA4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat EPHA4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q36.1   Ensembl cytogenetic band:  2q36.1   HGNC cytogenetic band: 2q36.3

EPHA4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
EPHA4 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02M222248:  view genomic region     (about GC identifiers)

Start:
222,282,747 bp from pter      End:
222,438,922 bp from pter
Size:
156,176 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: EPHA4_HUMAN, P54764 (See protein sequence)
Recommended Name: Ephrin type-A receptor 4 precursor  
Size: 986 amino acids; 109860 Da
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. 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
Selected PDB 3D structures from and Proteopedia for EPHA4 (see all 12):
2LW8 (3D)        2WO1 (3D)        2WO2 (3D)        2WO3 (3D)        3CKH (3D)        3GXU (3D)    
Secondary accessions: Q2M380

Explore the universe of human proteins at neXtProt for EPHA4: NX_P54764

Explore proteomics data for EPHA4 at MOPED

Post-translational modifications: 

  • Ubiquitination2 at Lys735
  • Glycosylation2 at Asn235, Asn340, Asn408, Asn545
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for EPHA4 (P54764) (see all 53)
     MSNQDVI  KERFIRE  PVMIITE  RDLAARN 


    See EPHA4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_004429.1  
    ENSEMBL proteins: 
     ENSP00000386276   ENSP00000386829   ENSP00000408145   ENSP00000395917   ENSP00000401405  
     ENSP00000391517   ENSP00000410158   ENSP00000444085   ENSP00000404089   ENSP00000281821  
     ENSP00000375923  

    EPHA4 Human Recombinant Protein Products:

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    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    Browse OriGene Protein Over-expression Lysates
    OriGene Custom MassSpec
    OriGene Custom Protein Services for EPHA4
    GenScript Custom Purified and Recombinant Proteins Services for EPHA4
    Novus Biologicals EPHA4 Proteins
    Browse Sino Biological Recombinant Proteins
    Sino Biological Cell Lysate for EPHA4
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for EPHA4

     
    Search eBioscience for Proteins for EPHA4 

    EPHA4 Antibody Products:

    Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
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    Cell Signaling Technology (CST) Antibodies for EPHA4 
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    OriGene Custom Antibody Services for EPHA4
    Novus Biologicals EPHA4 Antibodies
    Abcam antibodies for EPHA4 (P54764, P54756)
    Cloud-Clone Corp. Antibodies for EPHA4
    ThermoFisher Antibody for EPHA4
    LSBio Antibodies in human, mouse, rat for EPHA4

    EPHA4 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    GenScript EPHA4-Activity-based Kinase Assay for Compound Screening
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for EPHA4
    Cloud-Clone Corp. CLIAs for EPHA4
    Search eBioscience for ELISAs for EPHA4 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    FN3: Fibronectin type III domain containing
    EPH: EPH receptors
    SAMD: Sterile alpha motif (SAM) domain containing

    IUPHAR Guide to PHARMACOLOGY protein family classification: EPH receptor A4
    Ephrin receptor family
    Ephrin receptor family

    Selected InterPro protein domains (see all 16):
     IPR017441 Protein_kinase_ATP_BS
     IPR003961 Fibronectin_type3
     IPR011009 Kinase-like_dom
     IPR013783 Ig-like_fold
     IPR000719 Prot_kinase_dom

    Graphical View of Domain Structure for InterPro Entry P54764

    ProtoNet protein and cluster: P54764

    Selected Blocks protein domains (see all 6):
    IPB001090 Ephrin receptor
    IPB001426 Receptor tyrosine kinase
    IPB001660 Sterile alpha motif SAM
    IPB003962 Fibronectin type III repeat signature
    IPB008266 Tyrosine protein kinase


    UniProtKB/Swiss-Prot: EPHA4_HUMAN, P54764
    Domain: The protein kinase domain mediates interaction with NGEF (By similarity)
    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


    Find genes that share domains with EPHA4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: EPHA4_HUMAN, P54764
    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. Beside 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
    Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

         Enzyme Numbers (IUBMB): EC 2.7.10.11 2 EC 2.7.102

         Gene Ontology (GO): Selected molecular function terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity IDA12775584
    GO:0004713protein tyrosine kinase activity ----
    GO:0005003ephrin receptor activity ----
    GO:0005004GPI-linked ephrin receptor activity ISS--
    GO:0005005transmembrane-ephrin receptor activity ISS--
         
    Find genes that share ontologies with EPHA4           About GenesLikeMe


    Phenotypes:
         2 GenomeRNAi human phenotypes for EPHA4:
     Decreased telomerase activity  Upregulation of Wnt/beta-caten 

         6 MGI mutant phenotypes (inferred from 19 alleles(MGI details for Epha4):
     behavior/neurological  cellular  endocrine/exocrine gland  nervous system  normal 
     reproductive system 

    Find genes that share phenotypes with EPHA4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for EPHA4: Epha4tm1Byd Epha4tm2.1Kldr Epha4tm1Pvan

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for EPHA4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for EPHA4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for EPHA4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for EPHA4

    miRNA
    Products:
        
    miRTarBase miRNAs that target EPHA4:
    hsa-mir-21-5p (MIRT030703), hsa-mir-320a (MIRT044406), hsa-mir-93-5p (MIRT027959), hsa-mir-10a-5p (MIRT006972), hsa-mir-361-5p (MIRT044104), hsa-mir-130b-3p (MIRT020126), hsa-mir-92a-3p (MIRT049304), hsa-mir-505-3p (MIRT041039), hsa-mir-132-3p (MIRT021734), hsa-mir-10b-5p (MIRT047479), hsa-mir-335-5p (MIRT016908)

    Block miRNA regulation of human, mouse, rat EPHA4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate EPHA4 (see all 69):
    hsa-miR-607 hsa-miR-106a hsa-miR-374a hsa-miR-519a hsa-miR-4275 hsa-miR-93 hsa-miR-3613-3p hsa-miR-490-5p
    SwitchGear 3'UTR luciferase reporter plasmidEPHA4 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for EPHA4
    Predesigned siRNA for gene silencing in human, mouse, rat EPHA4

    Gene Editing
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    Clone
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    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: EPHA4 (NM_004438)
    Sino Biological Human cDNA Clone for EPHA4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for EPHA4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat EPHA4
    Addgene plasmids for EPHA4 

    Cell Line
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    Browse ESI BIO Cell Lines and PureStem Progenitors for EPHA4 
    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for EPHA4


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    EPHA4_HUMAN, P54764: Cell membrane; Single-pass type I membrane protein (By similarity). Cell projection, axon
    (By similarity). Cell projection, dendrite (By similarity). Cell junction, synapse, postsynaptic cell membrane,
    postsynaptic density (By similarity). Early endosome (By similarity). Note=Clustered upon activation and targeted
    to early endosome (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    endosome4
    cytoskeleton2
    endoplasmic reticulum2
    golgi apparatus2
    mitochondrion2
    extracellular1
    nucleus1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 21):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm ISS--
    GO:0005741mitochondrial outer membrane IEA--
    GO:0005783endoplasmic reticulum IEA--
    GO:0005794Golgi apparatus IEA--
    GO:0005886plasma membrane ----

    Find genes that share ontologies with EPHA4           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for EPHA4 About   (see all 21)  
    See pathways by source

    SuperPathContained pathways About
    1GPCR Pathway
    Ras Pathway0.73
    Breast Cancer Regulation by Stathmin10.58
    Paxillin Interactions0.73
    NFAT in Immune Response0.58
    GPCR Pathway0.62
    Estrogen Pathway0.55
    Pancreatic Adenocarcinoma0.59
    P2Y Receptor Signaling0.38
    2ERK Signaling
    Rho Family GTPases0.61
    Molecular Mechanisms of Cancer0.51
    ERK Signaling0.61
    ILK Signaling0.49
    MAPK Signaling0.58
    3Nanog in Mammalian ESC Pluripotency
    Nanog in Mammalian ESC Pluripotency0.61
    14-3-3 Induced Intracellular Signaling0.59
    GSK3 Signaling0.61
    eNOS Signaling0.48
    4Actin Nucleation by ARP-WASP Complex
    Actin Nucleation and Branching0.66
    CDC42 Pathway0.41
    Actin Nucleation by ARP-WASP Complex0.66
    5Activation of cAMP-Dependent PKA
    Activation of cAMP-Dependent PKA0.77
    Activation of PKA through GPCR0.71


    Find genes that share SuperPaths with EPHA4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for EPHA4 (see all 32)
        Paxillin Interactions
    Molecular Mechanisms of Cancer
    Intracellular Calcium Signaling
    JNK Pathway
    P2Y Receptor Signaling

    1 Cell Signaling Technology (CST) Pathway for EPHA4
        Tyrosine Kinases / Adaptors

    3 GeneGo (Thomson Reuters) Pathways for EPHA4
        Neurophysiological process Receptor-mediated axon growth repulsion
    G-protein signaling RhoA regulation pathway
    Cell adhesion Ephrins signaling

    3 BioSystems Pathways for EPHA4
        Spinal Cord Injury
    EPHA forward signaling
    EphrinA-EPHA pathway



    1 Kegg Pathway  (Kegg details for EPHA4):
        Axon guidance

        Pathway & Disease-focused RT2 Profiler PCR Array including EPHA4: 
              Polycomb & Trithorax Target Genes in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for EPHA4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for EPHA4 (P547643 ENSP000002818214) via UniProtKB, MINT, STRING, and/or I2D (see all 85)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HIST1H4AP628053I2D: score=2 
    HIST1H4BP628053I2D: score=2 
    HIST1H4CP628053I2D: score=2 
    HIST1H4DP628053I2D: score=2 
    HIST1H4EP628053I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 23):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006468protein phosphorylation ----
    GO:0007155cell adhesion IEA--
    GO:0007169transmembrane receptor protein tyrosine kinase signaling pathway ----
    GO:0007411axon guidance ----
    GO:0007628adult walking behavior IEA--

    Find genes that share ontologies with EPHA4           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for EPHA4

    2 HMDB Compounds for EPHA4    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    1 Novoseek inferred chemical compound relationship for EPHA4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 63.2 22 14742708 (2), 14697664 (1), 12775584 (1), 15136143 (1) (see all 14)



    Find genes that share compounds with EPHA4           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for EPHA4 gene: 
    NM_004438.3  

    Unigene Cluster for EPHA4:

    EPH receptor A4
    Hs.371218  [show with all ESTs]
    Unigene Representative Sequence: NM_004438
    15 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000469354 ENST00000472696 ENST00000409854 ENST00000409938 ENST00000424339
    ENST00000495693 ENST00000443796 ENST00000441679 ENST00000463446 ENST00000415749
    ENST00000419964 ENST00000541600 ENST00000434266 ENST00000281821(uc002vmr.2 uc002vmq.3 uc010zlm.1)
    ENST00000392071
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate EPHA4 (see all 69):
    hsa-miR-607 hsa-miR-106a hsa-miR-374a hsa-miR-519a hsa-miR-4275 hsa-miR-93 hsa-miR-3613-3p hsa-miR-490-5p
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    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector: EPHA4 (NM_004438)
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat EPHA4
    Addgene plasmids for EPHA4 
    Primer
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      QuantiTect SYBR Green Assays in human, mouse, rat EPHA4
      QuantiFast Probe-based Assays in human, mouse, rat EPHA4

    Additional mRNA sequence: 

    AF075040.1 AK225181.1 AK290306.1 AK300772.1 AK312380.1 BC016981.1 BC026327.1 BC105000.1 
    BC105002.1 L36645.1 

    9 DOTS entries:

    DT.308776  DT.100643773  DT.101981630  DT.114821  DT.91740624  DT.443224  DT.97786732  DT.121023444 
    DT.95157109 

    Selected AceView cDNA sequences (see all 128):

    AI168749 Z43829 BX642775 AI913604 BF371310 AI214293 BQ009361 BM724253 
    Z45177 AA972095 BP350809 L36645 AI815473 AF075040 BX642787 BE503900 
    BC026327 BM722126 NM_004438 BM679073 BX109749 AW440598 BM680394 AW608647 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for EPHA4 (see all 10)    About this scheme

    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:                                                                                                                                                            

    ExUns: 19 ^ 20a · 20b ^ 21a · 21b ^ 22 ^ 23 ^ 24
    SP1:              -                                 
    SP2:                                                
    SP3:                                                
    SP4:                                                
    SP5:                                                


    ECgene alternative splicing isoforms for EPHA4

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    EPHA4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AACTTTAGGT
    EPHA4 Expression
    About this image


    EPHA4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 23) fully expand
     
     Neurons
             Lateral Neurons of the LMC Lumbar Lateral Motor Division
     
     Spinal Cord (Nervous System)    fully expand to see all 3 entries
             Lateral Neurons of the LMC Lumbar Lateral Motor Division
     
     Limb (Muscoskeletal System)    fully expand to see all 4 entries
             Limb Muscle Progenitor Cells Forelimb Myotome
             Limb Bud
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 2 entries
             Limb Muscle Progenitor Cells Forelimb Myotome
     
     Neural Tube (Nervous System)    fully expand to see all 4 entries
             Metencephalon
             Floor plate-like cells
    EPHA4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    EPHA4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.371218

    UniProtKB/Swiss-Prot: EPHA4_HUMAN, P54764
    Tissue specificity: Ubiquitous

        Pathway & Disease-focused RT2 Profiler PCR Array including EPHA4: 
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for EPHA4 gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Epha41 , 5 Eph receptor A41, 5 90.67(n)1
    98.58(a)1
      1 (39.55 cM)5
    138381  NM_007936.31  NP_031962.21 
     773671855 
    chicken
    (Gallus gallus)
    Aves EPHA41 EPH receptor A4 83.47(n)
    94.22(a)
      395559  NM_204781.1  NP_990112.1 
    lizard
    (Anolis carolinensis)
    Reptilia EPHA46
    EPH receptor A4
    92(a)
    1 ↔ 1
    3(26102562-26280862)
    African clawed frog
    (Xenopus laevis)
    Amphibia MGC530382 hypothetical protein MGC53038 81.98(n)    L26099.1 
    zebrafish
    (Danio rerio)
    Actinopterygii rtk42 eph-like receptor tyrosine kinase 4 74.75(n)   30687  AJ005030.1 
    worm
    (Caenorhabditis elegans)
    Secernentea vab-11 vab-1 49.02(n)
    40.34(a)
      173794  NM_062405.5  NP_494806.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for EPHA4 gene
    EPHB12  EPHA22  EPHB32  EPHA52  EPHB62  EPHA62  EPHA12  EPHB22  
    EPHA82  EPHA32  EPHA72  EPHA102  EPHB42  
    Selected SIMAP similar genes for EPHA4 using alignment to 13 protein entries:     EPHA4_HUMAN (see all proteins) (see all similar genes):
    NTRK1    ERBB2    EPHA3    EGFR    ERBB3    EPHA7
    EPHA6    EPHB1    EPHA5    PTK2    EPHB2 variant protein    TXK
    EPHA8    EPHB2    A20    ALK    EML4-ALK    EZR-ROS1

    Find genes that share paralogs with EPHA4           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for EPHA4 (see all 3241)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0421364
    A bladder carcinoma NOS sample4--see VAR_0421362 G E mis40--------
    VAR_0421374
    A metastatic melanoma sample4--see VAR_0421372 S F mis40--------
    rs1907772471,2
    --222282361(+) CCACCA/GTTTGT 1 -- ds50010--------
    rs1415200041,2
    C--222282373(+) GAGTTC/GTGGCT 1 -- ds50010--------
    rs75700621,2
    C,F,A--222282387(+) TGTTAT/GACACT 1 -- ds500114Minor allele frequency- G:0.41NA WA CSA EA 510
    rs1117083811,2
    C,F--222282554(+) AATTAC/TGATGG 1 -- ds50012Minor allele frequency- T:0.50CSA 4
    rs75826601,2
    C,F,A--222282583(+) AATGCA/GTTGTT 1 -- ds50019Minor allele frequency- G:0.42NA WA CSA EA 370
    rs76094491,2
    C,F,A,H--222282591(+) GTTCTG/CAAGGG 1 -- ds500110Minor allele frequency- C:0.29EA NS NA WA CSA 536
    rs75826651,2
    C,F--222282593(+) TCTGAA/GGGGTG 1 -- ds50012Minor allele frequency- G:0.14WA 120
    rs1454501181,2
    C--222282601(+) GTGAAG/TAATCT 1 -- ds50010--------

    HapMap Linkage Disequilibrium report for EPHA4 (222282747 - 222438922 bp)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for EPHA4 (see all 11):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2657184CNV Deletion23128226
    esv2669891CNV Deletion23128226
    esv2721514CNV Deletion23290073
    esv2676923CNV Deletion23128226
    nsv3174CNV Insertion18451855
    nsv818114CNV Loss17921354
    nsv428407CNV Loss18775914
    nsv526093CNV Loss19592680
    nsv875891CNV Gain21882294
    essv11476CNV CNV17122850

    Human Gene Mutation Database (HGMD): EPHA4
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing EPHA4
    DNA2.0 Custom Variant and Variant Library Synthesis for EPHA4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 602188    OMIM disorders: --

    1 disease for EPHA4:    
    About MalaCards
    staphyloenterotoxemia

    2 diseases from the University of Copenhagen DISEASES database for EPHA4:
    Staphyloenterotoxemia     Toxic shock syndrome

    Find genes that share disorders with EPHA4           About GenesLikeMe

    1 Novoseek inferred disease relationship for EPHA4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tumors 0 2 18790757 (2)

    Genetic Association Database (GAD): EPHA4
    Human Genome Epidemiology (HuGE) Navigator: EPHA4 (3 documents)

    Export disorders for EPHA4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for EPHA4 gene, integrated from 10 sources (see all 118):
    (articles sorted by number of sources associating them with EPHA4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. (PubMed id 9267020)1, 2, 3 (Cell 1997)
    2. cDNA cloning and tissue distribution of five human EPH-like receptor protein-tyrosine kinases. (PubMed id 7898931)1, 2, 9 Fox G.M.... Welcher A.A. (Oncogene 1995)
    3. Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort. (PubMed id 20100581)1, 4 Shen L....Saykin A.J. (Neuroimage 2010)
    4. Neither replication nor simulation supports a role for the axon guidance pathway in the genetics of Parkinson's disease. (PubMed id 18628988)1, 4 Li Y....Hadjigeorgiou G. (PLoS ONE 2008)
    5. Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. (PubMed id 17143272)1, 2 Fu W.Y.... Ip N.Y. (Nat. Neurosci. 2007)
    6. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    7. Overexpression of EphA4 gene and reduced expression of EphB2 gene correlates with liver metastasis in colorectal cancer. (PubMed id 18695888)1, 9 Oshima T....Imada T. (Int. J. Oncol. 2008)
    8. Structural characterization of the EphA4-Ephrin-B2 complex reveals new features enabling Eph-ephrin binding promiscuity. (PubMed id 19875447)2, 9 Qin H.... Song J. (J. Biol. Chem. 2010)
    9. Overexpression of the receptor tyrosine kinase EphA4 in human gastric cancers. (PubMed id 18837080)1, 9 Oki M....Shinomura Y. (World J. Gastroenterol. 2008)
    10. Structural plasticity of EPH receptor A4 facilitates cross-class ephrin signaling. (PubMed id 19836338)2, 9 Bowden T.A.... Jones E.Y. (Structure 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 2043 HGNC: 3388 AceView: EPHA4 Ensembl:ENSG00000116106 euGenes: HUgn2043
    ECgene: EPHA4 Kegg: 2043 H-InvDB: EPHA4

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for EPHA4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for EPHA4 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for EPHA4 gene:
    Search GeneIP for patents involving EPHA4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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