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Protein

Ephrin-B2

Gene

EFNB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  1. ephrin receptor binding Source: UniProtKB

GO - Biological processi

  1. anatomical structure morphogenesis Source: ProtInc
  2. axon guidance Source: GO_Central
  3. cell adhesion Source: UniProtKB
  4. cell-cell signaling Source: ProtInc
  5. cell migration involved in sprouting angiogenesis Source: UniProtKB
  6. ephrin receptor signaling pathway Source: UniProtKB
  7. lymph vessel development Source: Ensembl
  8. negative regulation of keratinocyte proliferation Source: Ensembl
  9. organ morphogenesis Source: Ensembl
  10. positive regulation of cardiac muscle cell differentiation Source: BHF-UCL
  11. regulation of chemotaxis Source: UniProtKB
  12. viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Angiogenesis, Differentiation, Host-virus interaction, Neurogenesis

Enzyme and pathway databases

ReactomeiREACT_228085. EPHB-mediated forward signaling.
REACT_228170. EPH-Ephrin signaling.
REACT_228189. EPH-ephrin mediated repulsion of cells.
REACT_228226. Ephrin signaling.
SignaLinkiP52799.

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin-B2
Alternative name(s):
EPH-related receptor tyrosine kinase ligand 5
Short name:
LERK-5
HTK ligand
Short name:
HTK-L
Gene namesi
Name:EFNB2
Synonyms:EPLG5, HTKL, LERK5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 13

Organism-specific databases

HGNCiHGNC:3227. EFNB2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 229202ExtracellularSequence AnalysisAdd
BLAST
Transmembranei230 – 25021HelicalSequence AnalysisAdd
BLAST
Topological domaini251 – 33383CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. focal adhesion Source: UniProtKB
  2. integral component of plasma membrane Source: ProtInc
  3. plasma membrane Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi121 – 1222LW → YM: Complete loss of Nipah protein G binding. 1 Publication

Organism-specific databases

PharmGKBiPA27662.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 333306Ephrin-B2PRO_0000008392Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi36 – 361N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi62 ↔ 101
Disulfide bondi89 ↔ 153
Glycosylationi139 – 1391N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP52799.
PaxDbiP52799.
PeptideAtlasiP52799.
PRIDEiP52799.

PTM databases

PhosphoSiteiP52799.

Expressioni

Tissue specificityi

Lung and kidney.

Gene expression databases

BgeeiP52799.
CleanExiHS_EFNB2.
ExpressionAtlasiP52799. baseline and differential.
GenevestigatoriP52799.

Organism-specific databases

HPAiCAB009368.
HPA008999.

Interactioni

Subunit structurei

Interacts with PDZRN3 (By similarity). Binds to the receptor tyrosine kinases EPHA4, EPHB4 and EPHA3. Binds to Hendra virus and Nipah virus G protein.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NCK2O436397EBI-7532268,EBI-713635

Protein-protein interaction databases

BioGridi108268. 55 interactions.
DIPiDIP-46378N.
IntActiP52799. 1 interaction.
MINTiMINT-3019741.
STRINGi9606.ENSP00000245323.

Structurei

Secondary structure

1
333
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi30 – 367Combined sources
Turni44 – 463Combined sources
Beta strandi47 – 504Combined sources
Beta strandi57 – 626Combined sources
Beta strandi65 – 684Combined sources
Beta strandi75 – 817Combined sources
Helixi83 – 886Combined sources
Beta strandi98 – 1014Combined sources
Turni103 – 1053Combined sources
Beta strandi108 – 1169Combined sources
Beta strandi130 – 1356Combined sources
Helixi142 – 1443Combined sources
Beta strandi145 – 1495Combined sources
Helixi151 – 1555Combined sources
Beta strandi159 – 1646Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP52799.
SMRiP52799. Positions 25-166.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52799.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 164137Ephrin RBDPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi331 – 3333PDZ-bindingSequence Analysis

Sequence similaritiesi

Belongs to the ephrin family.PROSITE-ProRule annotation
Contains 1 ephrin RBD (ephrin receptor-binding) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG261641.
GeneTreeiENSGT00390000005839.
HOGENOMiHOG000220931.
HOVERGENiHBG051448.
InParanoidiP52799.
KOiK05463.
OMAiGSTRHND.
OrthoDBiEOG7288S5.
PhylomeDBiP52799.

Family and domain databases

Gene3Di2.60.40.420. 1 hit.
InterProiIPR008972. Cupredoxin.
IPR001799. Ephrin.
IPR019765. Ephrin_CS.
[Graphical view]
PANTHERiPTHR11304. PTHR11304. 1 hit.
PfamiPF00812. Ephrin. 1 hit.
[Graphical view]
PRINTSiPR01347. EPHRIN.
ProDomiPD002533. Ephrin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF49503. SSF49503. 1 hit.
PROSITEiPS01299. EPHRIN_RBD_1. 1 hit.
PS51551. EPHRIN_RBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P52799-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVRRDSVWK YCWGVLMVLC RTAISKSIVL EPIYWNSSNS KFLPGQGLVL
60 70 80 90 100
YPQIGDKLDI ICPKVDSKTV GQYEYYKVYM VDKDQADRCT IKKENTPLLN
110 120 130 140 150
CAKPDQDIKF TIKFQEFSPN LWGLEFQKNK DYYIISTSNG SLEGLDNQEG
160 170 180 190 200
GVCQTRAMKI LMKVGQDASS AGSTRNKDPT RRPELEAGTN GRSSTTSPFV
210 220 230 240 250
KPNPGSSTDG NSAGHSGNNI LGSEVALFAG IASGCIIFIV IIITLVVLLL
260 270 280 290 300
KYRRRHRKHS PQHTTTLSLS TLATPKRSGN NNGSEPSDII IPLRTADSVF
310 320 330
CPHYEKVSGD YGHPVYIVQE MPPQSPANIY YKV
Length:333
Mass (Da):36,923
Last modified:October 1, 1996 - v1
Checksum:i6D9932A632626AEA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9507.1.
PIRiI84743.
RefSeqiNP_004084.1. NM_004093.3.
UniGeneiHs.149239.

Genome annotation databases

EnsembliENST00000245323; ENSP00000245323; ENSG00000125266.
GeneIDi1948.
KEGGihsa:1948.
UCSCiuc001vqi.3. human.

Polymorphism databases

DMDMi1706673.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9507.1.
PIRiI84743.
RefSeqiNP_004084.1. NM_004093.3.
UniGeneiHs.149239.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP52799.
SMRiP52799. Positions 25-166.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108268. 55 interactions.
DIPiDIP-46378N.
IntActiP52799. 1 interaction.
MINTiMINT-3019741.
STRINGi9606.ENSP00000245323.

PTM databases

PhosphoSiteiP52799.

Polymorphism databases

DMDMi1706673.

Proteomic databases

MaxQBiP52799.
PaxDbiP52799.
PeptideAtlasiP52799.
PRIDEiP52799.

Protocols and materials databases

DNASUi1948.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245323; ENSP00000245323; ENSG00000125266.
GeneIDi1948.
KEGGihsa:1948.
UCSCiuc001vqi.3. human.

Organism-specific databases

CTDi1948.
GeneCardsiGC13M107142.
HGNCiHGNC:3227. EFNB2.
HPAiCAB009368.
HPA008999.
MIMi600527. gene.
neXtProtiNX_P52799.
PharmGKBiPA27662.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG261641.
GeneTreeiENSGT00390000005839.
HOGENOMiHOG000220931.
HOVERGENiHBG051448.
InParanoidiP52799.
KOiK05463.
OMAiGSTRHND.
OrthoDBiEOG7288S5.
PhylomeDBiP52799.

Enzyme and pathway databases

ReactomeiREACT_228085. EPHB-mediated forward signaling.
REACT_228170. EPH-Ephrin signaling.
REACT_228189. EPH-ephrin mediated repulsion of cells.
REACT_228226. Ephrin signaling.
SignaLinkiP52799.

Miscellaneous databases

ChiTaRSiEFNB2. human.
EvolutionaryTraceiP52799.
GeneWikiiEFNB2.
GenomeRNAii1948.
NextBioi7895.
PROiP52799.
SOURCEiSearch...

Gene expression databases

BgeeiP52799.
CleanExiHS_EFNB2.
ExpressionAtlasiP52799. baseline and differential.
GenevestigatoriP52799.

Family and domain databases

Gene3Di2.60.40.420. 1 hit.
InterProiIPR008972. Cupredoxin.
IPR001799. Ephrin.
IPR019765. Ephrin_CS.
[Graphical view]
PANTHERiPTHR11304. PTHR11304. 1 hit.
PfamiPF00812. Ephrin. 1 hit.
[Graphical view]
PRINTSiPR01347. EPHRIN.
ProDomiPD002533. Ephrin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF49503. SSF49503. 1 hit.
PROSITEiPS01299. EPHRIN_RBD_1. 1 hit.
PS51551. EPHRIN_RBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. 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.
    , 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. 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.

Entry informationi

Entry nameiEFNB2_HUMAN
AccessioniPrimary (citable) accession number: P52799
Secondary accession number(s): Q5JV56
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: February 4, 2015
This is version 136 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.