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P52799 (EFNB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ephrin-B2
Alternative name(s):
EPH-related receptor tyrosine kinase ligand 5
Short name=LERK-5
HTK ligand
Short name=HTK-L
Gene names
Name:EFNB2
Synonyms:EPLG5, HTKL, LERK5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length333 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors 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. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 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 from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons. Ref.6

Subunit structure

Interacts with PDZRN3 By similarity. Binds to the receptor tyrosine kinases EPHA4, EPHB4 and EPHA3. Binds to Hendra virus and Nipah virus G protein. Ref.7 Ref.8

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Lung and kidney.

Post-translational modification

Inducible phosphorylation of tyrosine residues in the cytoplasmic domain By similarity.

Sequence similarities

Belongs to the ephrin family.

Contains 1 ephrin RBD (ephrin receptor-binding) domain.

Ontologies

Keywords
   Biological processAngiogenesis
Differentiation
Host-virus interaction
Neurogenesis
   Cellular componentMembrane
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanatomical structure morphogenesis

Traceable author statement PubMed 9630219. Source: ProtInc

axon guidance

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell adhesion

Inferred from direct assay Ref.6. Source: UniProtKB

cell migration involved in sprouting angiogenesis

Inferred from direct assay Ref.6. Source: UniProtKB

cell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

ephrin receptor signaling pathway

Inferred from direct assay Ref.6. Source: UniProtKB

lymph vessel development

Inferred from electronic annotation. Source: Ensembl

negative regulation of keratinocyte proliferation

Inferred from electronic annotation. Source: Ensembl

organ morphogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of cardiac muscle cell differentiation

Inferred from sequence or structural similarity PubMed 17336907. Source: BHF-UCL

regulation of chemotaxis

Inferred from direct assay Ref.6. Source: UniProtKB

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentintegral component of plasma membrane

Traceable author statement PubMed 8660976. Source: ProtInc

plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionephrin receptor binding

Inferred from physical interaction Ref.10. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NCK2O436397EBI-7532268,EBI-713635

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Chain28 – 333306Ephrin-B2
PRO_0000008392

Regions

Topological domain28 – 229202Extracellular Potential
Transmembrane230 – 25021Helical; Potential
Topological domain251 – 33383Cytoplasmic Potential
Domain28 – 164137Ephrin RBD
Motif331 – 3333PDZ-binding Potential

Amino acid modifications

Glycosylation361N-linked (GlcNAc...) Potential
Glycosylation1391N-linked (GlcNAc...) Potential
Disulfide bond62 ↔ 101 Ref.10 Ref.12
Disulfide bond89 ↔ 153 Ref.10 Ref.12

Experimental info

Mutagenesis121 – 1222LW → YM: Complete loss of Nipah protein G binding. Ref.8

Secondary structure

............................. 333
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P52799 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 6D9932A632626AEA

FASTA33336,923
        10         20         30         40         50         60 
MAVRRDSVWK YCWGVLMVLC RTAISKSIVL EPIYWNSSNS KFLPGQGLVL YPQIGDKLDI 

        70         80         90        100        110        120 
ICPKVDSKTV GQYEYYKVYM VDKDQADRCT IKKENTPLLN CAKPDQDIKF TIKFQEFSPN 

       130        140        150        160        170        180 
LWGLEFQKNK DYYIISTSNG SLEGLDNQEG GVCQTRAMKI LMKVGQDASS AGSTRNKDPT 

       190        200        210        220        230        240 
RRPELEAGTN GRSSTTSPFV KPNPGSSTDG NSAGHSGNNI LGSEVALFAG IASGCIIFIV 

       250        260        270        280        290        300 
IIITLVVLLL KYRRRHRKHS PQHTTTLSLS TLATPKRSGN NNGSEPSDII IPLRTADSVF 

       310        320        330 
CPHYEKVSGD YGHPVYIVQE MPPQSPANIY YKV 

« Hide

References

« Hide 'large scale' references
[1]"Isolation of LERK-5: a ligand of the eph-related receptor tyrosine kinases."
Cerretti D.P., Vanden Bos T., Nelson N., Kozlosky C.J., Reddy P., Maraskovsky E., Park L.S., Lyman S.D., Copeland N.G., Gilbert D.J., Jenkins N.A., Fletcher R.A.
Mol. Immunol. 32:1197-1205(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Molecular cloning of a ligand for the EPH-related receptor protein-tyrosine kinase Htk."
Bennett B.D., Zeigler F.C., Gu Q., Fendly B., Goddard A.D., Gillett N., Matthews W.
Proc. Natl. Acad. Sci. U.S.A. 92:1866-1870(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"Overexpression of Lerk-5/Eplg5 messenger RNA: a novel marker for increased tumorigenicity and metastatic potential in human malignant melanomas."
Vogt T., Stolz W., Welsh J., Jung B., Kerbel R.S., Kobayashi H., Landthaler M., McClelland M.
Clin. Cancer Res. 4:791-797(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[6]"Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells."
Fueller T., Korff T., Kilian A., Dandekar G., Augustin H.G.
J. Cell Sci. 116:2461-2470(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ANGIOGENESIS.
[7]"EphrinB2 is the entry receptor for Nipah virus, an emergent deadly paramyxovirus."
Negrete O.A., Levroney E.L., Aguilar H.C., Bertolotti-Ciarlet A., Nazarian R., Tajyar S., Lee B.
Nature 436:401-405(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NIPAH VIRUS PROTEIN G.
[8]"Two key residues in ephrinB3 are critical for its use as an alternative receptor for Nipah virus."
Negrete O.A., Wolf M.C., Aguilar H.C., Enterlein S., Wang W., Muehlberger E., Su S.V., Bertolotti-Ciarlet A., Flick R., Lee B.
PLoS Pathog. 2:78-86(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NIPAH VIRUS PROTEIN G, MUTAGENESIS OF 121-LEU-TRP-122.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Structural and biophysical characterization of the EphB4*ephrinB2 protein-protein interaction and receptor specificity."
Chrencik J.E., Brooun A., Kraus M.L., Recht M.I., Kolatkar A.R., Han G.W., Seifert J.M., Widmer H., Auer M., Kuhn P.
J. Biol. Chem. 281:28185-28192(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 28-165 IN COMPLEX WITH EPHB4, DISULFIDE BONDS.
[11]"Structural basis of Nipah and Hendra virus attachment to their cell-surface receptor ephrin-B2."
Bowden T.A., Aricescu A.R., Gilbert R.J., Grimes J.M., Jones E.Y., Stuart D.I.
Nat. Struct. Mol. Biol. 15:567-572(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 28-165 IN COMPLEXES WITH NIPAH VIRUS AND HENDRA VIRUS GLYCOPROTEINS.
[12]"Structural plasticity of EPH receptor A4 facilitates cross-class ephrin signaling."
Bowden T.A., Aricescu A.R., Nettleship J.E., Siebold C., Rahman-Huq N., Owens R.J., Stuart D.I., Jones E.Y.
Structure 17:1386-1397(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 27-167 IN COMPLEX WITH EPHA4, DISULFIDE BONDS.
[13]"Structural characterization of the EphA4-Ephrin-B2 complex reveals new features enabling Eph-ephrin binding promiscuity."
Qin H., Noberini R., Huan X., Shi J., Pasquale E.B., Song J.
J. Biol. Chem. 285:644-654(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 27-169 IN COMPLEX WITH EPHA4.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U16797 mRNA. Translation: AAA99707.1.
L38734 mRNA. Translation: AAC41752.1.
U81262 mRNA. Translation: AAD03786.1.
AL138689 Genomic DNA. Translation: CAI39907.1.
BC069342 mRNA. Translation: AAH69342.1.
BC074856 mRNA. Translation: AAH74856.1.
BC074857 mRNA. Translation: AAH74857.1.
BC105955 mRNA. Translation: AAI05956.1.
BC105956 mRNA. Translation: AAI05957.1.
BC105957 mRNA. Translation: AAI05958.1.
PIRI84743.
RefSeqNP_004084.1. NM_004093.3.
UniGeneHs.149239.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2HLEX-ray2.05B28-165[»]
2I85NMR-A25-166[»]
2VSKX-ray3.30B/D28-165[»]
2VSMX-ray1.80B28-165[»]
2WO2X-ray2.45B27-167[»]
3GXUX-ray2.50B27-169[»]
ProteinModelPortalP52799.
SMRP52799. Positions 25-166.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108268. 4 interactions.
DIPDIP-46378N.
IntActP52799. 1 interaction.
MINTMINT-3019741.
STRING9606.ENSP00000245323.

PTM databases

PhosphoSiteP52799.

Polymorphism databases

DMDM1706673.

Proteomic databases

PaxDbP52799.
PeptideAtlasP52799.
PRIDEP52799.

Protocols and materials databases

DNASU1948.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000245323; ENSP00000245323; ENSG00000125266.
GeneID1948.
KEGGhsa:1948.
UCSCuc001vqi.3. human.

Organism-specific databases

CTD1948.
GeneCardsGC13M107142.
HGNCHGNC:3227. EFNB2.
HPACAB009368.
HPA008999.
MIM600527. gene.
neXtProtNX_P52799.
PharmGKBPA27662.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG261641.
HOGENOMHOG000220931.
HOVERGENHBG051448.
InParanoidP52799.
KOK05463.
OMAGSTRHND.
OrthoDBEOG7288S5.
PhylomeDBP52799.

Enzyme and pathway databases

SignaLinkP52799.

Gene expression databases

ArrayExpressP52799.
BgeeP52799.
CleanExHS_EFNB2.
GenevestigatorP52799.

Family and domain databases

Gene3D2.60.40.420. 1 hit.
InterProIPR008972. Cupredoxin.
IPR001799. Ephrin.
IPR019765. Ephrin_CS.
[Graphical view]
PANTHERPTHR11304. PTHR11304. 1 hit.
PfamPF00812. Ephrin. 1 hit.
[Graphical view]
PRINTSPR01347. EPHRIN.
ProDomPD002533. Ephrin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMSSF49503. SSF49503. 1 hit.
PROSITEPS01299. EPHRIN_RBD_1. 1 hit.
PS51551. EPHRIN_RBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP52799.
GeneWikiEFNB2.
GenomeRNAi1948.
NextBio7895.
PROP52799.
SOURCESearch...

Entry information

Entry nameEFNB2_HUMAN
AccessionPrimary (citable) accession number: P52799
Secondary accession number(s): Q5JV56
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM