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EPHB4 Gene

protein-coding   GIFtS: 73
GCID: GC07M100402

EPH Receptor B4

(Previous name: EphB4)
(Previous symbol: HTK)
  See EPHB4-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 B41 2     Ephrin Receptor EphB42
HTK1 2 3 5     Ephrin Type-B Receptor 42
MYK12 3 5     Soluble EPHB4 Variant 12
Hepatoma Transmembrane Kinase2 3     Soluble EPHB4 Variant 22
Tyrosine-Protein Kinase TYRO112 3     Soluble EPHB4 Variant 32
TYRO112 3     Tyrosine-Protein Kinase Receptor HTK2
EC 2.7.10.13 8     EC 2.7.108
EphB41     

External Ids:    HGNC: 33951   Entrez Gene: 20502   Ensembl: ENSG000001964117   OMIM: 6000115   UniProtKB: P547603   

Export aliases for EPHB4 gene to outside databases

Previous GC identifers: GC07M098934 GC07M099997 GC07M100011 GC07M100044 GC07M100238 GC07M095030


(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 EPHB4 Gene:
Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the
nervous system. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A
(EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B
(EFNB) class, which are transmembrane proteins. The Eph family of 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. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein
encoded by this gene binds to ephrin-B2 and plays an essential role in vascular development. (provided by RefSeq,
Jul 2008)

GeneCards Summary for EPHB4 Gene:
EPHB4 (EPH receptor B4) is a protein-coding gene. Diseases associated with EPHB4 include prostate cancer. GO annotations related to this gene include ephrin receptor activity and transmembrane receptor protein tyrosine kinase activity. An important paralog of this gene is EPHB1.

UniProtKB/Swiss-Prot: EPHB4_HUMAN, P54760
Function: Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Together with its cognate ligand/functional ligand EFNB2
plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell
migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation form EFNB2-expressing
cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus
important in the context of tumor angiogenesis

summary for EPHB4 Gene:
Ephrins are a family of receptor tyrosine kinases (RTKs) that influence cell migration. In conjunction with
the ephrin ligands, ephrin receptors are involved in a variety of developmental events. EphB4 is
overexpressed in many tumor types, including breast and prostate cancer.

Gene Wiki entry for EPHB4 (EPH receptor B4) 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_000007.13  NC_018918.2  NT_007933.16  
Regulatory elements:
   Regulatory transcription factor binding sites in the EPHB4 gene promoter:
         AP-2rep   AREB6   p53   AP-1   p300   Lmo2   E47   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidEPHB4 promoter sequence
   Search Chromatin IP Primers for EPHB4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat EPHB4


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

Entrez Gene cytogenetic band: 7q22   Ensembl cytogenetic band:  7q22.1   HGNC cytogenetic band: 7q22

EPHB4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
EPHB4 gene location

GeneLoc information about chromosome 7         GeneLoc Exon Structure

GeneLoc location for GC07M100402:  view genomic region     (about GC identifiers)

Start:
100,400,187 bp from pter      End:
100,425,143 bp from pter
Size:
24,957 bases      Orientation:
minus strand

1 alternative location:
Chr7-,CRA_TCAG 99,759,792-99,784,748     

(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., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: EPHB4_HUMAN, P54760 (See protein sequence)
Recommended Name: Ephrin type-B receptor 4 precursor  
Size: 987 amino acids; 108270 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 (By similarity)
Developmental stage: Expressed in fetal heart, lung, liver and to a lower extent in brain. Not expressed in adult
brain
Selected PDB 3D structures from and Proteopedia for EPHB4 (see all 18):
2BBA (3D)        2E7H (3D)        2HLE (3D)        2QKQ (3D)        2VWU (3D)        2VWV (3D)    
Secondary accessions: Q9BTA5 Q9BXP0

Explore the universe of human proteins at neXtProt for EPHB4: NX_P54760

Explore proteomics data for EPHB4 at MOPED

Post-translational modifications: 

  • Phosphorylated; autophosphorylation is stimulated by EFNB21
  • Glycosylation2 at Asn203, Asn335, Asn426
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for EPHB4 (P54760) (see all 25)
     MSNQDVI  RDLAARN  SDPTYTS  QLMLDCW 


    See EPHB4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_004435.3  
    ENSEMBL proteins: 
     ENSP00000353833   ENSP00000350896  

    EPHB4 Human Recombinant Protein Products:

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    Novus Biologicals EPHB4 Proteins
    Novus Biologicals EPHB4 Lysate
    Browse Sino Biological Recombinant Proteins
    Sino Biological Cell Lysate for EPHB4
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for EPHB4

     
    Search eBioscience for Proteins for EPHB4 

     
    antibodies-online proteins for EPHB4 (7 products) 

     
    antibodies-online peptides for EPHB4

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    antibodies-online antibodies for EPHB4 (101 products) 

    EPHB4 Assay Products:

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    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for EPHB4
    Cloud-Clone Corp. CLIAs for EPHB4
    Search eBioscience for ELISAs for EPHB4 
    antibodies-online kits for EPHB4 (5 products) 


    (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 B4
    Ephrin receptor family
    Ephrin receptor family

    Selected InterPro protein domains (see all 18):
     IPR017441 Protein_kinase_ATP_BS
     IPR003961 Fibronectin_type3
     IPR021129 SAM_type1
     IPR011009 Kinase-like_dom
     IPR013783 Ig-like_fold

    Graphical View of Domain Structure for InterPro Entry P54760

    ProtoNet protein and cluster: P54760

    5 Blocks protein domains:
    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: EPHB4_HUMAN, P54760
    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 EPHB4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, 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: EPHB4_HUMAN, P54760
    Function: Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Together with its cognate ligand/functional ligand EFNB2
    plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell
    migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation form EFNB2-expressing
    cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus
    important in the context of tumor angiogenesis
    Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

         Genatlas biochemistry entry for EPHB4:
    EPH-related tyrosine kinase receptor,binding ephrin B4,expressed in projecting neurons and their target
    fields,involved in short-range contact-mediated axonal guidance,also involved in angiogenesis by marking venous
    but not arterial endothelial cells

         Enzyme Numbers (IUBMB): EC 2.7.10.11 2 EC 2.7.102

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004713protein tyrosine kinase activity ----
    GO:0004714transmembrane receptor protein tyrosine kinase activity IDA8188704
    GO:0005003ephrin receptor activity IDA12734395
    GO:0005515protein binding IPI16867992
         
    Find genes that share ontologies with EPHB4           About GenesLikeMe


    Phenotypes:
         3 GenomeRNAi human phenotypes for EPHB4:
     Decreased focal adhesion (FA)   Increased cell death in HCT116  Increased colony dispersion (i 

         5 MGI mutant phenotypes (inferred from 1 allele(MGI details for Ephb4):
     cardiovascular system  embryogenesis  growth/size/body  mortality/aging  muscle 

    Find genes that share phenotypes with EPHB4           About GenesLikeMe

    Animal Models:
       genOway: Develop your customized and physiologically relevant rodent model for EPHB4

    miRNA
    Products:
        
    miRTarBase miRNAs that target EPHB4:
    hsa-mir-20b-5p (MIRT006338), hsa-mir-1260b (MIRT052757), hsa-mir-93-3p (MIRT038783), hsa-mir-335-5p (MIRT017978)

    Block miRNA regulation of human, mouse, rat EPHB4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate EPHB4 (see all 39):
    hsa-miR-300 hsa-miR-106a hsa-miR-3653 hsa-miR-624 hsa-miR-301a hsa-miR-519a hsa-miR-124 hsa-miR-9
    SwitchGear 3'UTR luciferase reporter plasmidEPHB4 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for EPHB4
    Predesigned siRNA for gene silencing in human, mouse, rat EPHB4

    Gene Editing
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    Clone
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    GenScript: all cDNA clones in your preferred vector: EPHB4 (NM_004444)
    Sino Biological Human cDNA Clone for EPHB4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for EPHB4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat EPHB4
    Addgene plasmids for EPHB4 

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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for EPHB4


    (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
    EPHB4_HUMAN, P54760: Cell membrane; Single-pass type I membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    extracellular2
    cytoskeleton1
    cytosol1
    lysosome1
    peroxisome1

    Gene Ontology (GO): 1 cellular component term:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005887integral component of plasma membrane IDA8188704

    Find genes that share ontologies with EPHB4           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 EPHB4 About   (see all 14)  
    See pathways by source

    SuperPathContained pathways About
    1EphB-EphrinB Signaling
    EphB-EphrinB Signaling0.58
    Cytoskeleton remodeling Reverse signaling by ephrin B0.34
    Ephrin-Eph Signaling0.58
    2EPHB forward signaling
    EPHB forward signaling0.30
    EphrinB-EPHB pathway0.00
    Cell adhesion Ephrins signaling0.30
    3GPCR 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
    4ERK Signaling
    Rho Family GTPases0.61
    Molecular Mechanisms of Cancer0.51
    ERK Signaling0.61
    ILK Signaling0.49
    MAPK Signaling0.58
    5Nanog in Mammalian ESC Pluripotency
    Nanog in Mammalian ESC Pluripotency0.61
    14-3-3 Induced Intracellular Signaling0.59
    GSK3 Signaling0.61
    eNOS Signaling0.48


    Find genes that share SuperPaths with EPHB4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for EPHB4 (see all 31)
        MAPK Signaling
    Paxillin Interactions
    Endothelin-1 Signaling Pathway
    Molecular Mechanisms of Cancer
    Ephrin-Eph Signaling

    2 GeneGo (Thomson Reuters) Pathways for EPHB4
        Cytoskeleton remodeling Reverse signaling by ephrin B
    Cell adhesion Ephrins signaling

    3 BioSystems Pathways for EPHB4
        Ephrin B reverse signaling
    EPHB forward signaling
    EphrinB-EPHB pathway



    1 Kegg Pathway  (Kegg details for EPHB4):
        Axon guidance

        Pathway & Disease-focused RT2 Profiler PCR Array including EPHB4: 
              Angiogenesis in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for EPHB4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 15)

    Selected Interacting proteins for EPHB4 (P547603 ENSP000003508964) via UniProtKB, MINT, STRING, and/or I2D (see all 15)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    GRIN1Q055863, ENSP000003606164I2D: score=2 STRING: ENSP00000360616
    SDC3O750563, ENSP000003444684I2D: score=2 STRING: ENSP00000344468
    EFNB2P527993, ENSP000002453234I2D: score=1 STRING: ENSP00000245323
    JUNP054123, ENSP000003602664I2D: score=1 STRING: ENSP00000360266
    EGFRP005333, ENSP000002754934I2D: score=1 STRING: ENSP00000275493
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001525angiogenesis ISS--
    GO:0002042cell migration involved in sprouting angiogenesis IDA12734395
    GO:0003007heart morphogenesis ISS--
    GO:0006468protein phosphorylation ----
    GO:0007155cell adhesion IDA12734395

    Find genes that share ontologies with EPHB4           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 

    Compounds for EPHB4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    GTP 14564Class III receptor tyrosine kinase (RTK) inhibitor[34823-86-4]
    NVP BHG 712Potent EphB4 kinase inhibitor[940310-85-0]
    Ki 20227c-Fms inhibitor; suppresses osteolysis and osteoclast accumulation[623142-96-1]

    2 HMDB Compounds for EPHB4    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--

    8 DrugBank Compounds for EPHB4    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    3-({4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZAMIDE-- --target--10592235
    3-({4-[(5-chloro-1,3-benzodioxol-4-yl)amino]pyrimidin-2-yl}amino)benzenesulfonamide-- --target--10592235
    N'-(3-CHLORO-4-METHOXY-PHENYL)-N-(3,4,5-TRIMETHOXYPHENYL)-1,3,5-TRIAZINE-2,4-DIAMINE-- --target--10592235
    N'-(5-CHLORO-1,3-BENZODIOXOL-4-YL)-N-(3,4,5- TRIMETHOXYPHENYL)PYRIMIDINE-2,4-DIAMINE-- --target--10592235
    N'-(5-CHLORO-1,3-BENZODIOXOL-4-YL)-N-(3-MORPHOLIN-4-YLPHENYL)PYRIMIDINE-2,4-DIAMINE-- --target--10592235
    N'-(5-chloro-1,3-benzodioxol-4-yl)-N-(3-methylsulfonylphenyl)pyrimidine-2,4-diamine-- --target--10592235
    N-(5-chloro-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-amine-- --target--10592235
    N-[3-[[4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL]AMINO]PHENYL]METHANESULFONAMIDE-- --target--10592235

    3 Novoseek inferred chemical compound relationships for EPHB4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 66 35 8188704 (4), 10221518 (3), 15358160 (2), 16816380 (2) (see all 16)
    vegf 40.8 10 20338920 (3), 19950560 (1), 19923070 (1), 15471957 (1) (see all 6)
    thymidine 38.9 9 7593001 (2), 7969135 (1), 10502302 (1), 10639574 (1) (see all 6)



    Find genes that share compounds with EPHB4           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 EPHB4 gene: 
    NM_004444.4  

    Unigene Cluster for EPHB4:

    EPH receptor B4
    Hs.437008  [show with all ESTs]
    Unigene Representative Sequence: AB209644
    9 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000360620 ENST00000358173(uc003uwn.1 uc010lhj.1 uc011kkf.1 uc011kkg.1 uc011kkh.1)
    ENST00000487222(uc003uwm.1) ENST00000492403 ENST00000478459 ENST00000467515
    ENST00000477446 ENST00000489808 ENST00000492878
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate EPHB4 (see all 39):
    hsa-miR-300 hsa-miR-106a hsa-miR-3653 hsa-miR-624 hsa-miR-301a hsa-miR-519a hsa-miR-124 hsa-miR-9
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      QuantiTect SYBR Green Assays in human, mouse, rat EPHB4
      QuantiFast Probe-based Assays in human, mouse, rat EPHB4

    Additional mRNA sequence: 

    AB209644.1 AK301224.1 AY056048.1 BC004264.1 BC052804.1 EU826608.1 EU826609.1 EU826610.1 
    U07695.1 

    12 DOTS entries:

    DT.100689231  DT.100818782  DT.444136  DT.121068866  DT.100818780  DT.121068891  DT.95282899  DT.121068837 
    DT.97845932  DT.91914735  DT.95081702  DT.95282873 

    188 AceView cDNA sequences (see top 24):

    BM929429 BM790755 BE466828 BM830054 AV708776 AW083751 BM823021 H89196 
    BM766839 AY056048 BM742052 AW276575 BM766176 BM756028 AA369508 BM757081 
    BM974102 BM857398 AA659141 BM852162 AA299650 BU683397 BM795543 AI270622 
    AI281014 BM856991 BC052804 NM_004444 AW589657 AI273230 CA487258 BQ670731 
    BM771479 BC004264 AW449338 AA677904 CR620724 CR621822 AU133418 AW024723 
    BQ183584 CK820751 AI368193 BM765976 CR602699 BF475845 BM811595 AI092064 
    AL552477 AL554027 AL571512 AW008338 BI259712 U07695 BX445134 BU633245 
    AI093758 BG574591 CD618775 BI255547 BE538724 AI373252 BE535493 BQ880789 
    BM855413 AL550560 AL574393 AI479291 BI713495 AI279650 BG179940 BE294204 
    BX420733 AU127108 BX329102 BU193134 AL547693 AI991490 BG741269 AA557320 
    BQ026769 CK820752 CF128593 BX402660 AI335535 BU185546 BE742288 AI346123 
    BG251483 AI864099 AI968235 BM757088 BF725165 BG742352 BM790987 BU684593 
    BX435580 AA297708 AW511390 BG171180 BF968854 CN483625 AA640623 BX474046 
    AA304498 AA233517 AI796934 BI713759 BF568364 AL572602 BF984946 BE732736 
    BI094063 BQ720925 BE882482 AL575772 AW194707 BG033034 BE876882 AU149813 
    AL545808 AA582238 AA715499 BI838784 AI872428 BE538646 AA233516 CD618773 
    AI948725 AW058248 CB962032 AA298037 BE295690 CD618771 BF033764 BF339567 
    AL577000 AL036867 CK299090 W94076 BM753234 BM854921 BI825234 BM809867 
    CA489776 BE908908 AW605622 BG987835 CB959548 AA604556 BI087914 AW939393 
    CF593765 BE741965 BF569141 AI261660 BF036123 BM019732 BM808460 AW577701 
    BF766205 AI565315 AL554205 AI935559 CO401326 AI961137 AU154759 AW939912 
    W94075 N76569 R31503 AA095256 AL135127 AA299649 AL576867 AW577699 
    BU556655 AW382334 BE713295 BE163836 BE615143 H65580 BG339648 BF132857 
    AV735133 BG034781 BF507640 T51895 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for EPHB4 (see all 6)    About this scheme

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


    ECgene alternative splicing isoforms for EPHB4

    (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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    EPHB4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TCTGTTTCCA
    EPHB4 Expression
    About this image


    EPHB4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Endothelium (Cardiovascular System)    fully expand to see all 4 entries
             Venous Endothelial Cells Pulmonary Capillary Plexus
             Endothelial-like cells
     
     Lung (Respiratory System)    fully expand to see all 2 entries
             Venous Endothelial Cells Pulmonary Capillary Plexus
     
     Heart (Cardiovascular System)
             Venous Endothelial Cells Cardinal Veins
     
     NULL (Uncategorized)
             Endothelial-like cells
    EPHB4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    EPHB4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.437008

    UniProtKB/Swiss-Prot: EPHB4_HUMAN, P54760
    Tissue specificity: Abundantly expressed in placenta but also detected in kidney, liver, lung, pancreas, skeletal
    muscle and heart. Expressed in primitive and myeloid, but not lymphoid, hematopoietic cells. Also observed in
    cell lines derived from liver, breast, colon, lung, melanocyte and cervix

        Pathway & Disease-focused RT2 Profiler PCR Array including EPHB4: 
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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)
    About This Section

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    This gene was present in the common ancestor of animals.

    Orthologs for EPHB4 gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Ephb41 , 5 Eph receptor B41, 5 86.47(n)1
    93.11(a)1
      5 (76.38 cM)5
    138461  NM_001159571.11  NP_001153043.11 
     1373501095 
    African clawed frog
    (Xenopus laevis)
    Amphibia ephB4a2 eph receptor tyrosine kinase 75.82(n)    AJ236867.1 
    zebrafish
    (Danio rerio)
    Actinopterygii AJ005026.22   -- 78.6(n)   30688  AJ005026.2 
    fruit fly
    (Drosophila melanogaster)
    Insecta Eph3 protein amino acid phosphorylation
    transmembrane more
    38(a)
    (best of 2)
      102C2   --


    ENSEMBL Gene Tree for EPHB4 (if available)
    TreeFam Gene Tree for EPHB4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for EPHB4 gene
    EPHB12  EPHA22  EPHB32  EPHA42  EPHA52  EPHB62  EPHA62  EPHA12  
    EPHB22  EPHA82  EPHA32  EPHA72  EPHA102  
    Selected SIMAP similar genes for EPHB4 using alignment to 7 protein entries:     EPHB4_HUMAN (see all proteins) (see all similar genes):
    EPHB3    EPHB1    EPHB2 variant protein    EPHA2    EPHA3    EPHA4
    EPHA7    EPHB2    EPHA6    EPHA8    FRK    EPHA5
    HCK    YES1    EPHA10    EPHB6    LCK    LYN

    Find genes that share paralogs with EPHB4           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 EPHB4 (see all 754)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0421884
    A gastric adenocarcinoma sample4--see VAR_0421882 R W mis40--------
    VAR_0421834
    A metastatic melanoma sample4--see VAR_0421832 P L mis40--------
    rs2004882591,2
    C--95055009(+) CCCCC-/CGCAAGG 1 -- int10--------
    rs1149419421,2
    C--100399695(+) CACACA/GTGGGG 1 -- ds50010--------
    rs746262601,2
    C,F--100399697(+) CACGTG/TGGGGG 1 -- ds50011Minor allele frequency- T:0.10WA 118
    rs117732811,2
    H--100399704(+) GGGGGG/TCCCTT 1 -- ds50010--------
    rs559822651,2
    C,F--100399802(+) TCCATC/TCACGG 1 -- ds50013Minor allele frequency- T:0.08WA NA EA 358
    rs1489635661,2
    --100399805(+) ATCCAC/TGGAAC 1 -- ds50010--------
    rs1909626041,2
    --100400105(+) TCCAGA/CCCTCT 1 -- ds50010--------
    rs559455031,2
    C--100400124(+) TCGGTA/C/GAGCCA 1 -- ds50015WA CSA NA EA 362

    HapMap Linkage Disequilibrium report for EPHB4 (100400187 - 100425143 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 7 variations for EPHB4:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2734888CNV Deletion23290073
    dgv7403n71CNV Loss21882294
    dgv7402n71CNV Loss21882294
    nsv470381CNV Loss18288195
    nsv888800CNV Loss21882294
    nsv888796CNV Loss21882294
    dgv2119e1CNV Complex17122850

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing EPHB4
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    (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.)
    About This Section

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    OMIM gene information: 600011    OMIM disorders: --

    1 disease for EPHB4:    
    About MalaCards
    prostate cancer

    1 disease from the University of Copenhagen DISEASES database for EPHB4:
    Cancer

    Find genes that share disorders with EPHB4           About GenesLikeMe

    Selected Novoseek inferred disease relationships for EPHB4 gene (see all 22)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    retinal neovascularization 61.7 1 15914639 (1)
    neovascularization 52.9 2 17133777 (1), 17510705 (1)
    hnscc 47 24 16615113 (4), 17043250 (4), 18794445 (4), 14661437 (2)
    cancer 32.9 14 19552627 (3), 17108150 (1), 19879134 (1), 17241664 (1) (see all 9)
    proliferative diabetic retinopathy 31.3 1 17133777 (1)
    tumors 29.5 59 16816380 (4), 19366806 (4), 16615113 (3), 20133814 (3) (see all 26)
    endometrial carcinoma 25.2 4 11295082 (2), 12562648 (1)
    carcinoma squamous cell 24.1 8 16615113 (2), 17043250 (2), 18794445 (2), 17611172 (1) (see all 5)
    retinopathy 21.2 5 15914639 (2), 15289137 (1), 20503366 (1), 19232363 (1)
    ovarian cancer 20 10 18231102 (4), 17353927 (2), 18281782 (2)

    Genetic Association Database (GAD): EPHB4
    Human Genome Epidemiology (HuGE) Navigator: EPHB4 (1 document)

    Export disorders for EPHB4 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 EPHB4 gene, integrated from 10 sources (see all 177):
    (articles sorted by number of sources associating them with EPHB4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cloning and characterization of HTK, a novel transmembrane tyrosine kinase of the EPH subfamily. (PubMed id 8188704)1, 2, 3, 9 Bennett B.D.... Scadden D.T. (J. Biol. Chem. 1994)
    2. Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells. (PubMed id 12734395)1, 2, 9 Fueller T.... Augustin H.G. (J. Cell Sci. 2003)
    3. Structural and biophysical characterization of the EphB4*ephrinB2 protein-protein interaction and receptor specificity. (PubMed id 16867992)1, 2, 9 Chrencik J.E.... Kuhn P. (J. Biol. Chem. 2006)
    4. EphB4 controls blood vascular morphogenesis during postnatal angiogenesis. (PubMed id 16424904)1, 2, 9 Erber R.... Vajkoczy P. (EMBO J. 2006)
    5. EPHB4 gene polymorphisms and risk of intracranial hemorrhage in patients with brain arteriovenous malformations. (PubMed id 20031623)1, 4 Weinsheimer S....Young W.L. (Circ Cardiovasc Genet 2009)
    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. Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5. (PubMed id 11239002)1, 2 Wilson M.D.... Koop B.F. (Nucleic Acids Res. 2001)
    8. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee. (PubMed id 9267020)1, 2 (Cell 1997)
    9. Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells. (PubMed id 11929761)1, 9 Wang Z....Scadden D.T. (Blood 2002)
    10. EphB4 expression and biological significance in prostate cancer. (PubMed id 15930280)1, 9 Xia G....Gill P.S. (Cancer Res. 2005)

    (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: 2050 HGNC: 3395 AceView: EPHB4 Ensembl:ENSG00000196411 euGenes: HUgn2050
    ECgene: EPHB4 Kegg: 2050 H-InvDB: EPHB4

    (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 EPHB4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for EPHB4 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section

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    Patent Information for EPHB4 gene:
    Search GeneIP for patents involving EPHB4

    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, eBioscience, antibodies-online, 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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