EPHB4

Protein identityUniProt · HPA

UniProt accession

P54760

Gene

EPHB4

Ensembl

ENSG00000196411

Chromosome

7

Canonical length

987 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

987 residues, UniProt reviewed canonical sequence.

>P54760|EPHB4
     1  MELRVLLCWA SLAAALEETL LNTKLETADL KWVTFPQVDG QWEELSGLDE EQHSVRTYEV
    61  CDVQRAPGQA HWLRTGWVPR RGAVHVYATL RFTMLECLSL PRAGRSCKET FTVFYYESDA
   121  DTATALTPAW MENPYIKVDT VAAEHLTRKR PGAEATGKVN VKTLRLGPLS KAGFYLAFQD
   181  QGACMALLSL HLFYKKCAQL TVNLTRFPET VPRELVVPVA GSCVVDAVPA PGPSPSLYCR
   241  EDGQWAEQPV TGCSCAPGFE AAEGNTKCRA CAQGTFKPLS GEGSCQPCPA NSHSNTIGSA
   301  VCQCRVGYFR ARTDPRGAPC TTPPSAPRSV VSRLNGSSLH LEWSAPLESG GREDLTYALR
   361  CRECRPGGSC APCGGDLTFD PGPRDLVEPW VVVRGLRPDF TYTFEVTALN GVSSLATGPV
   421  PFEPVNVTTD REVPPAVSDI RVTRSSPSSL SLAWAVPRAP SGAVLDYEVK YHEKGAEGPS
   481  SVRFLKTSEN RAELRGLKRG ASYLVQVRAR SEAGYGPFGQ EHHSQTQLDE SEGWREQLAL
   541  IAGTAVVGVV LVLVVIVVAV LCLRKQSNGR EAEYSDKHGQ YLIGHGTKVY IDPFTYEDPN
   601  EAVREFAKEI DVSYVKIEEV IGAGEFGEVC RGRLKAPGKK ESCVAIKTLK GGYTERQRRE
   661  FLSEASIMGQ FEHPNIIRLE GVVTNSMPVM ILTEFMENGA LDSFLRLNDG QFTVIQLVGM
   721  LRGIASGMRY LAEMSYVHRD LAARNILVNS NLVCKVSDFG LSRFLEENSS DPTYTSSLGG
   781  KIPIRWTAPE AIAFRKFTSA SDAWSYGIVM WEVMSFGERP YWDMSNQDVI NAIEQDYRLP
   841  PPPDCPTSLH QLMLDCWQKD RNARPRFPQV VSALDKMIRN PASLKIVARE NGGASHPLLD
   901  QRQPHYSAFG SVGEWLRAIK MGRYEESFAA AGFGSFELVS QISAEDLLRI GVTLAGHQKK
   961  ILASVQHMKS QAKPGTPGGT GGPAPQY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against EPHB4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

56 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about EPHB4.

Disease | AllUniProt

Conditions EPHB4 is implicated in, by any mechanism.

• Lymphatic malformation 7 (LMPHM7) MIM:617300
• Capillary malformation-arteriovenous malformation 2 (CMAVM2) MIM:618196

Disease | GeneticClinVar

136 pathogenic / likely-pathogenic of 1,114 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Capillary malformation-arteriovenous malformation 2
• Lymphatic malformation 7
• EPHB4-related disorder
• Cardiovascular phenotype
• Capillary malformation-arteriovenous malformation syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.42

gnomAD pLI

0.01

gnomAD missense Z

2.3

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• cell adhesion
• cell migration involved in sprouting angiogenesis
• ephrin receptor signaling pathway
• heart morphogenesis

Molecular functions

• ATP binding
• ephrin receptor activity
• transmembrane receptor protein tyrosine kinase activity

Cellular components

• cytosol
• extracellular exosome
• extracellular region
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Ephrin, ligand binding domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Tyrosine-protein kinase, receptor class V, conserved site
• Sterile alpha motif domain
• Fibronectin type III
• Tyrosine-protein kinase, active site
• Galactose-binding-like domain superfamily
• Growth factor receptor cysteine-rich domain superfamily
• Protein kinase-like domain superfamily
• Tyrosine-protein kinase ephrin type A/B receptor-like
• Sterile alpha motif/pointed domain superfamily
• Immunoglobulin-like fold
• Ephrin receptor type-A /type-B
• Protein kinase, ATP binding site
• Tyrosine-protein kinase, catalytic domain
• Ephrin, transmembrane domain
• Fibronectin type III superfamily
• Ephrin receptor tyrosine kinases
• Fibronectin type III domain
• SAM domain (Sterile alpha motif)
• Ephrin receptor ligand binding domain
• Tyrosine-protein kinase ephrin type A/B receptor-like
• Protein tyrosine and serine/threonine kinase
• Ephrin type-A receptor 2 transmembrane domain
• Ephrin cysteine rich domain
• Ephrin type-B receptor 4, ligand binding domain
• EPH-B4, SAM domain

KeywordsUniProt

• Angiogenesis
• ATP-binding
• Cell membrane
• Developmental protein
• Disulfide bond
• Glycoprotein
• Kinase
• Membrane
• Nucleotide-binding
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transferase
• Transmembrane
• Transmembrane helix
• Tyrosine-protein kinase

InteractionsUniProt · HPA

Protein binding partners of EPHB4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RASA1
• EFNB2
• EPHA7