EPHB4 Gene
protein-coding GIFtS : 69 GCID: GC07 M100402
EPH receptor B4 EphB4 )HTK )
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Aliasesfor EPHB4 gene
(According to
1 HGNC ,
2 Entrez Gene ,
3 UniProtKB/Swiss-Prot ,
4 UniProtKB/TrEMBL , 5 OMIM , 6 GeneLoc ,
7 Ensembl ,
8 DME ,
9 miRBase ,
and/or 10 fRNAdb )About This Section Aliases EPH Receptor B4 1 2 Tyro111 HTK1 2 3 5 Ephrin Receptor EphB42 MYK12 3 5 Ephrin Type-B Receptor 42 Hepatoma Transmembrane Kinase2 3 Soluble EPHB4 Variant 12 Tyrosine-Protein Kinase TYRO112 3 Soluble EPHB4 Variant 22 TYRO112 3 Soluble EPHB4 Variant 32 EC 2.7.10.13 8 Tyrosine-Protein Kinase Receptor HTK2 EphB41 EC 2.7.108
Export aliases for EPHB4 gene to outside databases Previous GC identifers: GC07M098934 GC07M099997 GC07M100011 GC07M100044 GC07M100238 GC07M095030
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Summariesfor EPHB4 gene (According to Entrez Gene ,
Tocris Bioscience ,
Wikipedia's
Gene Wiki ,
PharmGKB ,UniProtKB/Swiss-Prot ,
and/or
UniProtKB/TrEMBL )
About This Section Entrez Gene summary for EPHB4 : 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) UniProtKB/Swiss-Prot: EPHB4_HUMAN, P54760 Function : Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacentcells, 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 : Ephrins are a family of receptor tyrosine kinases (RTKs) that influence cell migration. In conjunction withthe ephrin ligands, ephrin receptors are involved in a variety of developmental events. EphB4 isoverexpressed in many tumor types, including breast and prostate cancer. Gene Wiki entry for EPHB4 (EPH receptor B4)
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Genomic Viewsfor EPHB4 gene
(According to
GeneLoc and/or
HGNC , and/or
Entrez Gene (NCBI build 37) ,miRBase ,UCSC (hg19) and
Ensembl (release 69) ,
Regulatory elements and Epigenetics data according to
QIAGEN ,
SABiosciences , and/or
SwitchGear Genomics )About This Section RefSeq DNA sequence: NC_000007.13 NC_018918.1 NT_007933.15 NT_079595.2 Regulatory elements: SABiosciences Regulatory transcription factor binding sites in the EPHB4 gene promoter:AP-2rep AREB6 p53 AP-1 p300 Lmo2 E47 Other transcription factors Search SABiosciences Chromatin IP Primers for EPHB4 Epigenetics: QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human mouse rat
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
Entrez Gene Ensembl 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 : Chr 7-,CRA_TCAG 99,759,792-99,784,748
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Proteinsfor EPHB4 gene
(According to
1 UniProtKB ,
HORDE ,
neXtProt ,
Ensembl ,
and/or Reactome ,
Modification sites according to 2 PhosphoSitePlus ,
Specific Peptides from DME ,
Protein expression images according to data from SPIRE MOPED and PaxDb ,
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 , and/or
Uscn ,
EMD Millipore ,
R&D Systems ,
OriGene ,
GenScript ,
Cell Signaling Technology ,
Enzo Life Sciences , and/or
Uscn ,
Ontologies according to Gene
Ontology Consortium 01 Mar 2013 and
Entrez Gene ,
Antibodies by
EMD Millipore ,
R&D Systems ,
GenScript ,
Cell Signaling Technology ,
OriGene ,
Novus Biologicals ,
Thermo Fisher Scientific ,
Abcam , and/or
Uscn )
About This Section UniProtKB/Swiss-Prot: EPHB4_HUMAN, P54760 See
protein sequence )Recommended Name: Size : 987 amino acids; 108270 DaSubunit : Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptordimer. Oligomerization is probably required to induce biological responses (By similarity)
Subcellular location : Cell membrane; Single-pass type I membrane proteinDevelopmental stage : Expressed in fetal heart, lung, liver and to a lower extent in brain. Not expressed in adult brain6/15 PDB 3D structures from (see all 15 ):2BBA (3D) 2E7H (3D) 2HLE (3D) 2QKQ (3D) 2VWU (3D) 2VWV (3D) Secondary accessions : Q9BTA5 Q9BXP0Explore the universe of human proteins at neXtProt for EPHB4: NX_P54760 Post-translational modifications:
Phosphorylated; autophosphorylation is stimulated by EFNB21 View modification sites using PhosphoSitePlus 2 View neXtProt modification sites for NX_P54760 4/25 DME Specific Peptides for EPHB4 (P54760 ) (see all 25 )EPHB4 Protein expression data from MOPED and PaxDb : About this image REFSEQ proteins: NP_004435.3 ENSEMBL proteins: ENSP00000353833 ENSP00000350896 Human Recombinant Protein Products: Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view) : About this table
About GeneDecksing EPHB4 Antibody Products: Assay Products for EPHB4:
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Protein
Domains /for EPHB4 gene (According to InterPro , ProtoNet ,
UniProtKB , and/or BLOCKS ,
Sets of similar genes according to GeneDecks )
About This Section About GeneDecksing 5/16 InterPro domains/families (see all 16 ):
Graphical View of Domain Structure for InterPro Entry P54760 ProtoNet protein and cluster: P54760
5 Blocks protein families : IPB001090 IPB001426 IPB001660 IPB003962 IPB008266 UniProtKB/Swiss-Prot: EPHB4_HUMAN, P54760 Similarity : Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamilySimilarity : Contains 1 Eph LBD (Eph ligand-binding) domainSimilarity : Contains 2 fibronectin type-III domainsSimilarity : Contains 1 protein kinase domainSimilarity : Contains 1 SAM (sterile alpha motif) domain
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Functionfor EPHB4 gene
(According to 1 UniProtKB ,
Genatlas ,
LifeMap Discovery™ ,
IUBMB , and/or
2 DME ,
Human phenotypes from GenomeRNAi ,
Animal models from MGI Mar 06 2013,
SABiosciences ,
miRNA Gene Targets from miRTarBase
shRNA from
OriGene ,
RNAi from
EMD Millipore ,
siRNAs from
OriGene ,
QIAGEN ,
microRNA from QIAGEN ,
Gene Editing from DNA2.0 ,
Clones from EMD Millipore ,
OriGene ,
SwitchGear Genomics ,
GenScript ,
Sino Biological ,
DNA2.0 ,
and Vector BioLabs ,
Cell Lines from GenScript ,
LifeMap BioReagents ,
In Situ Hybridization Assays from Advanced Cell Diagnostics ,
Ontologies according to Gene Ontology Consortium 01 Mar 2013 via
Entrez Gene .)
About This Section Function Summary: UniProtKB/Swiss-Prot: EPHB4_HUMAN, P54760 Function : Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacentcells, 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 2.7.10.1 1 2 EC 2.7.10 2 Clone Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human mouse rat see all 4 )human mouse rat see all 2 )OriGene custom cloning services – gene synthesis, subcloning, mutagenesis,
variant library, vector shuttling 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
In Situ AssayAdvanced Cell Diagnostics RNAscope RNA in situ hybridization assays for EPHB4
Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view) : About this table
About GeneDecksing 3 GenomeRNAi human phenotypes for EPHB4 :Animal Models: 5 MGI mutant phenotypes (inferred from 1 allele(MGI details for Ephb4) :About GeneDecksing
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Pathways & Interactionsfor EPHB4 gene
(Pathways according to
EMD Millipore ,
R&D Systems ,
Cell Signaling Technology ,
KEGG ,
PharmGKB ,
BioSystems ,
Reactome ,
Tocris Bioscience ,
GeneGo (Thomson Reuters) ,
QIAGEN ,
and/or UniProtKB ,
Sets of similar genes according to GeneDecks ,
Interaction Networks according to
SABiosciences ,
and/or STRING ,
Interactions according to 1 UniProtKB ,
2 MINT ,
3 I2D , and/or
4 STRING ,
with links to IntAct and
Ensembl ,
Ontologies according to Gene Ontology Consortium 01 Mar 2013 via
Entrez Gene) .
About This Section Unified GeneCards pathways - 5/16 super-pathways (see all 16 ) About this table See pathways by source Super-pathway contained gene-specific pathways 1 GPCR Pathway 2 Rho Family GTPases 3 Nanog in Mammalian ESC Pluripotency 4 Actin Nucleation by ARP-WASP Complex 5 Cell adhesion_Ephrins signaling
Pathway sources See GeneCards unified pathways Show all pathways 2 5/31 (see all 31 )2 3 1 (Kegg details for EPHB4) :About GeneDecksing Interactions: SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for EPHB4 STRING Interaction
Network Preview (showing 5 interactants - click image to see 15)5/15 Interacting proteins for EPHB4 (P54760 3 ENSP00000350896 4 via UniProtKB, MINT, STRING , and/or I2D (see all 15 )About this table Gene Ontology (GO): 5/6 biological process terms (GO ID links to tree view) (see all 6 ): About this table
About GeneDecksing
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Drugs & Compoundsfor EPHB4 gene (Chemical Compounds according to UniProtKB , Enzo Life Sciences ,
EMD Millipore , Tocris Bioscience
HMDB ,
BitterDB , and/or
Novoseek , and Drugs according to
DrugBank ,
Enzo Life Sciences , and/or
PharmGKB , with drugs/clinical trials/news
search links to CenterWatch )
About This Section About GeneDecksing Compounds for EPHB4 available from Tocris Bioscience About this table Compound Action
CAS
# NVP BHG 712 Potent EphB4 kinase inhibitor [940310-85-0]
2 HMDB Compounds for EPHB4 About this table 8 DrugBank Compounds for EPHB4 About this table Compound Synonyms
CAS
# Type Actions PubMed 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 chemical compound relationships for EPHB4 gene About this table EPHB4
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Transcriptsfor EPHB4 gene (Secondary structures according to
fRNAdb ,Unigene
(Build 235 Homo sapiens; Mar 10 2013) or GenBank , Entrez Gene ,
DOTS (version 10), and/or
AceView ,
transcript ids from Ensembl
with links to UCSC , GeneLoc ,
alternative splicing isoforms according to ASD and/or
ECgene ,EMD Millipore ,
OriGene ,
QIAGEN ,
shRNA from
OriGene ,
microRNA from QIAGEN ,
OriGene ,
SwitchGear Genomics ,
GenScript ,
DNA2.0 ,
Vector BioLabs ,
Primers from
OriGene ,
SABiosciences , and/or
QIAGEN
)About This Section 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 Clone OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human mouse rat see all 4 )human mouse rat see all 2 )OriGene custom cloning services – gene synthesis, subcloning, mutagenesis,
variant library, vector shuttling GenScript: all cDNA clones in your preferred vector: EPHB4 (NM_004444 ) DNA2.0 Custom Codon Optimized Gene
Synthesis Service for EPHB4 Vector BioLabs ready-to-use adenovirus/AAV for human , mouse , rat EPHB4
Additional cDNA 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 24/188 AceView cDNA sequences (see all 188 ):
BM771479 BU683397 AW024723 BM857398 AW589657 AV708776 BM766176 AI368193 BM823021 AI273230 AI281014 AI270622 AA659141 BM757081 AW449338 CK820751 BM856991 CR621822 BQ670731 BE466828 CA487258 BM742052 BC004264 BM830054 GeneLoc Exon Structure 5/6 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
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Expression for EPHB4 gene
(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™ ,
plus additional links to
Genevestigator , and/or
SOURCE , and/or
BioGPS , and/or
UniProtKB ,SABiosciences ,
Primers from
OriGene ,
SABiosciences , and/or
QIAGEN ,
In Situ Hybridization Assays from Advanced Cell Diagnostics )
About This Section EPHB4 expression in normal human tissues (normalized intensities) See probesets specificity/sensitivity at GeneAnnot About this image BioGPS CGAP TAG: TCTGTTTCCA
About this image EPHB4 expression in embryonic tissues and stem cells About this table See EPHB4 Protein Expression from SPIRE MOPED and PaxDB Genevestigator expression for EPHB4 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, skeletalmuscle 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 SABiosciences Expression via Pathway-Focused PCR Array including EPHB4 : Primer OriGene genome-wide validated SYBR primer pairs in human mouse rat Browse OriGene validated miRNA SYBR primer pairs SABiosciences RT2 qPCR Primer Assay in human mouse rat QIAGEN QuantiTect SYBR Green Assays in human mouse rat QIAGEN QuantiFast Probe-based Assays in human mouse rat In Situ Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for EPHB4
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Orthologsfor EPHB4 gene
(Orthologs according to
1,2 HomoloGene (2 older version, for species not in 1 newer version),
3 euGenes ,
4 SGD
,
5 MGI Mar 06 2013,
with possible further links to
Flybase
and/or
WormBase ,
and/or
6 Ensembl pan taxonomic compara ,
Gene Trees according to Ensembl and
TreeFam )
About This Section Orthologs for EPHB4 gene from 5/20 species (see all 20 ) About this table
Organism
Taxonomic
Gene
Description
Human
Orthology
Details
lizard Reptilia EPHA66
--
58(a)
1 ↔ 1
GL344569.1(5445-27408)
African clawed frog Amphibia ephB4a2
eph receptor tyrosine kinase
75.82(n)
AJ236867.1
zebrafish Actinopterygii AJ005026.22
--
78.6(n)
30688 AJ005026.2
fruit fly Insecta Eph3
protein amino acid phosphorylationmore
38(a)
102C2 --
worm Secernentea vab-16 6 see all 6 )
protein KINase family member (kin-24)(see all 6 )
28(a) 17(a) (see all 6 )
possible orthologpossible ortholog(see all 6 )
II(4571997-4591357) IV(9839089-9841052)
ENSEMBL Gene Tree for EPHB4 (if available)TreeFam Gene Tree for EPHB4 (if available)
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Paralogsfor EPHB4 gene (Paralogs according to
1 HomoloGene ,2 Ensembl , and 3 SIMAP , Pseudogenes according to 4 Pseudogene.org Build 68)About This Section Paralogs for EPHB4 gene EPHB1 2 EPHA2 2 EPHB3 2 EPHA4 2 EPHA5 2 EPHB6 2 EPHA6 2 EPHB2 2 EPHA1 2 EPHA8 2 EPHA3 2 EPHA7 2 EPHA10 2 18/23 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 About GeneDecksing
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Genomic Variantsfor EPHB4 gene (SNPs/Variants according to the
1 NCBI SNP Database ,
2 Ensembl ,
3 PupaSUITE ,
UniProtKB , 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) and the Locus Specific Mutation
Databases (LSDB) , Blood group antigen gene mutations by BGMUT ,
Resequencing Primers from QIAGEN ,
Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences )
About This Section Genomic Data Transcription Related Data Allele Frequencies SNP ID Valid Clinical Chr 7 pos Sequence # AA Type More # Allele Pop Total More
summary
for 
and Proteopedia 
for EPHB4 (
Kegg Pathway 
Expression by the Database of Embryonic development, Stem cell research, and
Regenerative medicine 
Anatomical Compartment 
Negative
Microarrays
In-situ hybridization
