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Aliases for EPHB4 Gene

Aliases for EPHB4 Gene

  • EPH Receptor B4 2 3 5
  • Tyrosine-Protein Kinase TYRO11 3 4
  • Hepatoma Transmembrane Kinase 3 4
  • EC 2.7.10.1 4 63
  • TYRO11 3 4
  • MYK1 3 4
  • HTK 3 4
  • Tyrosine-Protein Kinase Receptor HTK 3
  • Soluble EPHB4 Variant 1 3
  • Soluble EPHB4 Variant 2 3
  • Soluble EPHB4 Variant 3 3
  • Ephrin Receptor EphB4 3
  • EC 2.7.10 63
  • EphB4 2

External Ids for EPHB4 Gene

Previous HGNC Symbols for EPHB4 Gene

  • HTK

Previous GeneCards Identifiers for EPHB4 Gene

  • GC07M098934
  • GC07M099997
  • GC07M100011
  • GC07M100044
  • GC07M100238
  • GC07M100402
  • GC07M095030

Summaries for EPHB4 Gene

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 squamous cell carcinoma, head and neck and endometrial cancer. Among its related pathways are EphB-EphrinB Signaling and Developmental Biology. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is EPHA3.

UniProtKB/Swiss-Prot for EPHB4 Gene

  • 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.

Tocris Summary for EPHB4 Gene

Gene Wiki entry for EPHB4 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EPHB4 Gene

Genomics for EPHB4 Gene

Regulatory Elements for EPHB4 Gene

Promoters for EPHB4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around EPHB4 on UCSC Golden Path with GeneCards custom track

Genomic Location for EPHB4 Gene

Chromosome:
7
Start:
100,802,565 bp from pter
End:
100,827,521 bp from pter
Size:
24,957 bases
Orientation:
Minus strand

Genomic View for EPHB4 Gene

Genes around EPHB4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EPHB4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EPHB4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EPHB4 Gene

Proteins for EPHB4 Gene

  • Protein details for EPHB4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P54760-EPHB4_HUMAN
    Recommended name:
    Ephrin type-B receptor 4
    Protein Accession:
    P54760
    Secondary Accessions:
    • B5A970
    • B5A971
    • B5A972
    • Q7Z635
    • Q9BTA5
    • Q9BXP0

    Protein attributes for EPHB4 Gene

    Size:
    987 amino acids
    Molecular mass:
    108270 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 (By similarity).

    Three dimensional structures from OCA and Proteopedia for EPHB4 Gene

    Alternative splice isoforms for EPHB4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for EPHB4 Gene

Proteomics data for EPHB4 Gene at MOPED

Post-translational modifications for EPHB4 Gene

  • Phosphorylated; autophosphorylation is stimulated by EFNB2.
  • Glycosylation at Asn 203, Asn 335, and Asn 426
  • Modification sites at PhosphoSitePlus

Other Protein References for EPHB4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for EPHB4 (EphB4)

Domains & Families for EPHB4 Gene

Graphical View of Domain Structure for InterPro Entry

P54760

UniProtKB/Swiss-Prot:

EPHB4_HUMAN :
  • Contains 1 Eph LBD (Eph ligand-binding) domain.
  • Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.
Domain:
  • 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 EPHB4: view

Function for EPHB4 Gene

Molecular function for EPHB4 Gene

GENATLAS Biochemistry:
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
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for EPHB4 Gene

Gene Ontology (GO) - Molecular Function for EPHB4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004713 protein tyrosine kinase activity IEA --
GO:0005003 ephrin receptor activity IEA,IDA 12734395
genes like me logo Genes that share ontologies with EPHB4: view
genes like me logo Genes that share phenotypes with EPHB4: view

Animal Models for EPHB4 Gene

MGI Knock Outs for EPHB4:

Animal Model Products

  • Taconic Biosciences Mouse Models for EPHB4

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for EPHB4 Gene

Localization for EPHB4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EPHB4 Gene

Cell membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for EPHB4 Gene COMPARTMENTS Subcellular localization image for EPHB4 gene
Compartment Confidence
cytosol 5
extracellular 5
plasma membrane 5
cytoskeleton 1
lysosome 1
peroxisome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for EPHB4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with EPHB4: view

Pathways & Interactions for EPHB4 Gene

genes like me logo Genes that share pathways with EPHB4: view

SIGNOR curated interactions for EPHB4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for EPHB4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis ISS --
GO:0006468 protein phosphorylation IEA --
GO:0007411 axon guidance TAS --
GO:0046777 protein autophosphorylation IDA 8188704
GO:0048013 ephrin receptor signaling pathway IEA,TAS --
genes like me logo Genes that share ontologies with EPHB4: view

Drugs & Compounds for EPHB4 Gene

(12) Drugs for EPHB4 Gene - From: HMDB, DGIdb, DrugBank, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
3-({4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZAMIDE Experimental Pharma Target 0
3-({4-[(5-chloro-1,3-benzodioxol-4-yl)amino]pyrimidin-2-yl}amino)benzenesulfonamide Experimental Pharma Target 0
N'-(3-CHLORO-4-METHOXY-PHENYL)-N-(3,4,5-TRIMETHOXYPHENYL)-1,3,5-TRIAZINE-2,4-DIAMINE Experimental Pharma Target 0
N-(5-chloro-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-amine Experimental Pharma Target 0

(4) Additional Compounds for EPHB4 Gene - From: HMDB, Tocris, and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
KYL
676657-00-4
NVP BHG 712
940310-85-0
genes like me logo Genes that share compounds with EPHB4: view

Transcripts for EPHB4 Gene

Unigene Clusters for EPHB4 Gene

EPH receptor B4:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for EPHB4 Gene

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: -
SP6:

Relevant External Links for EPHB4 Gene

GeneLoc Exon Structure for
EPHB4
ECgene alternative splicing isoforms for
EPHB4

Expression for EPHB4 Gene

mRNA expression in normal human tissues for EPHB4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for EPHB4 Gene

This gene is overexpressed in Urine (32.5) and Uterus (7.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for EPHB4 Gene



SOURCE GeneReport for Unigene cluster for EPHB4 Gene Hs.437008

mRNA Expression by UniProt/SwissProt for EPHB4 Gene

P54760-EPHB4_HUMAN
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.
genes like me logo Genes that share expression patterns with EPHB4: view

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues and Protein tissue co-expression partners for EPHB4 Gene

Orthologs for EPHB4 Gene

This gene was present in the common ancestor of animals.

Orthologs for EPHB4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia EPHB4 35
  • 90.68 (n)
  • 96.05 (a)
EPHB4 36
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia EPHB4 35
  • 89.36 (n)
  • 96.86 (a)
EPHB4 36
  • 97 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Ephb4 35
  • 86.47 (n)
  • 93.11 (a)
Ephb4 16
Ephb4 36
  • 92 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia EPHB4 35
  • 99.7 (n)
  • 100 (a)
EPHB4 36
  • 100 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia EPHB4 36
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia EPHB4 36
  • 88 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Ephb4 35
  • 86.16 (n)
  • 93.32 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.3205 35
African clawed frog
(Xenopus laevis)
Amphibia ephB4a 35
zebrafish
(Danio rerio)
Actinopterygii -- 35
ephb4a 36
  • 62 (a)
OneToMany
ephb4b 36
  • 60 (a)
OneToMany
ephb4a 35
  • 64.1 (n)
  • 64.06 (a)
fruit fly
(Drosophila melanogaster)
Insecta Eph 37
  • 38 (a)
hop 37
  • 35 (a)
Eph 36
  • 36 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 42 (a)
ManyToMany
-- 36
  • 39 (a)
ManyToMany
CSA.1664 36
  • 38 (a)
ManyToMany
CSA.7809 36
  • 37 (a)
ManyToMany
Species with no ortholog for EPHB4:
  • 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)
  • chicken (Gallus gallus)
  • 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)
  • lizard (Anolis carolinensis)
  • 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 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)
  • worm (Caenorhabditis elegans)

Evolution for EPHB4 Gene

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

Paralogs for EPHB4 Gene

Paralogs for EPHB4 Gene

genes like me logo Genes that share paralogs with EPHB4: view

Variants for EPHB4 Gene

Sequence variations from dbSNP and Humsavar for EPHB4 Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type
rs34653459 - 100,823,855(+) GGCCC(A/G)GGGCA reference, missense
rs55866373 - 100,823,718(+) GAAGA(C/T)GGTGA reference, missense
VAR_042183 A metastatic melanoma sample
rs55720981 - 100,819,742(+) AGGGC(A/G)CACAG reference, missense
rs36050247 - 100,813,680(+) TGTTT(C/G)TCCGA reference, missense

Structural Variations from Database of Genomic Variants (DGV) for EPHB4 Gene

Variant ID Type Subtype PubMed ID
esv2734888 CNV Deletion 23290073
nsv470381 CNV Loss 18288195
nsv888796 CNV Loss 21882294
dgv2119e1 CNV Complex 17122850
dgv7402n71 CNV Loss 21882294
dgv7403n71 CNV Loss 21882294
nsv888800 CNV Loss 21882294

Variation tolerance for EPHB4 Gene

Residual Variation Intolerance Score: 13% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.88; 48.45% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for EPHB4 Gene

HapMap Linkage Disequilibrium report
EPHB4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for EPHB4 Gene

Disorders for EPHB4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for EPHB4 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
squamous cell carcinoma, head and neck
  • squamous cell carcinoma, head and neck, somatic
endometrial cancer
  • endometrial cancer, familial
microvascular complications of diabetes 1
  • diabetic nephropathy
- elite association - COSMIC cancer census association via MalaCards
Search EPHB4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for EPHB4

Genetic Association Database (GAD)
EPHB4
Human Genome Epidemiology (HuGE) Navigator
EPHB4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
EPHB4
genes like me logo Genes that share disorders with EPHB4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for EPHB4 Gene

Publications for EPHB4 Gene

  1. Cloning and characterization of HTK, a novel transmembrane tyrosine kinase of the EPH subfamily. (PMID: 8188704) Bennett B.D. … Scadden D.T. (J. Biol. Chem. 1994) 2 3 4 23 67
  2. BCR-ABL-independent and RAS / MAPK pathway-dependent form of imatinib resistance in Ph-positive acute lymphoblastic leukemia cell line with activation of EphB4. (PMID: 20002159) Suzuki M. … Naoe T. (Eur. J. Haematol. 2010) 3 23
  3. Aberrant DNA methylation and epigenetic inactivation of Eph receptor tyrosine kinases and ephrin ligands in acute lymphoblastic leukemia. (PMID: 20061560) Kuang S.Q. … Garcia-Manero G. (Blood 2010) 3 23
  4. Novel EphB4 monoclonal antibodies modulate angiogenesis and inhibit tumor growth. (PMID: 20133814) Krasnoperov V. … Gill P.S. (Am. J. Pathol. 2010) 3 23
  5. Coexpression of EphB4 and ephrinB2 in tumor advancement of uterine cervical cancers. (PMID: 19356789) Alam S.M. … Tamaya T. (Gynecol. Oncol. 2009) 3 23

Products for EPHB4 Gene

Sources for EPHB4 Gene

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