P52799 (EFNB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	EFNB2
Synonyms:	EPLG5, HTKL, LERK5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	333 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Angiogenesis Differentiation Host-virus interaction Neurogenesis
Cellular component	Membrane
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell adhesion Inferred from direct assay Ref.6. Source: UniProtKB cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW 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: Compara nervous system development Inferred from electronic annotation. Source: UniProtKB-KW organ morphogenesis Inferred from electronic annotation. Source: Compara 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 virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to plasma membrane Traceable author statement PubMed 8660976. Source: ProtInc
Molecular_function	ephrin receptor binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 27

27

Potential

Chain

28 – 333

306

Ephrin-B2

PRO_0000008392

Regions

Topological domain

28 – 229

202

Extracellular Potential

Transmembrane

230 – 250

21

Helical; Potential

Topological domain

251 – 333

83

Cytoplasmic Potential

Domain

28 – 164

137

Ephrin RBD

Motif

331 – 333

3

PDZ-binding Potential

Amino acid modifications

Glycosylation

36

1

N-linked (GlcNAc...) Potential

Glycosylation

139

1

N-linked (GlcNAc...) Potential

Disulfide bond

62 ↔ 101

Ref.10 Ref.12

Disulfide bond

89 ↔ 153

Ref.10 Ref.12

Experimental info

Mutagenesis

121 – 122

2

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

Secondary structure

1

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333

Helix Strand Turn

Details...

Beta strand

30 – 36

7

Turn

44 – 46

3

Beta strand

47 – 50

4

Beta strand

57 – 62

6

Beta strand

65 – 68

4

Beta strand

75 – 81

7

Helix

83 – 88

6

Beta strand

98 – 101

4

Turn

103 – 105

3

Beta strand

108 – 116

9

Beta strand

130 – 135

6

Helix

142 – 144

3

Beta strand

145 – 149

5

Helix

151 – 155

5

Beta strand

159 – 164

6

Sequences

	Sequence		Length	Mass (Da)
	P52799 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 6D9932A632626AEA	FASTA	333	36,923
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00005126.

PIR

I84743.

RefSeq

NP_004084.1. NM_004093.3.

UniGene

Hs.149239.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2HLE	X-ray	2.05	B	28-165	[»]
2I85	NMR	-	A	25-166	[»]
2VSK	X-ray	3.30	B/D	28-165	[»]
2VSM	X-ray	1.80	B	28-165	[»]
2WO2	X-ray	2.45	B	27-167	[»]
3GXU	X-ray	2.50	B	27-169	[»]

ProteinModelPortal

P52799.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46378N.

STRING

9606.ENSP00000245323.

PTM databases

PhosphoSite

P52799.

Polymorphism databases

DMDM

1706673.

Proteomic databases

PaxDb

P52799.

PeptideAtlas

P52799.

PRIDE

P52799.

Protocols and materials databases

DNASU

1948.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000245323; ENSP00000245323; ENSG00000125266.

GeneID

1948.

KEGG

hsa:1948.

UCSC

uc001vqi.3. human.

Organism-specific databases

CTD

1948.

GeneCards

GC13M107142.

HGNC

HGNC:3227. EFNB2.

HPA

CAB009368.
HPA008999.

MIM

600527. gene.

neXtProt

NX_P52799.

PharmGKB

PA27662.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG261641.

HOGENOM

HOG000220931.

HOVERGEN

HBG051448.

InParanoid

P52799.

KO

K05463.

OMA

GSTRHND.

OrthoDB

EOG402WSK.

PhylomeDB

P52799.

Enzyme and pathway databases

Pathway_Interaction_DB

ephbfwdpathway. EPHB forward signaling.
ephrinbrevpathway. Ephrin B reverse signaling.
ephrinb_ephbpathway. EphrinB-EPHB pathway.

Gene expression databases

ArrayExpress

P52799.

Bgee

P52799.

CleanEx

HS_EFNB2.

Genevestigator

P52799.

GermOnline

ENSG00000125266. Homo sapiens.

Family and domain databases

Gene3D

2.60.40.420. 1 hit.

InterPro

IPR008972. Cupredoxin.
IPR001799. Ephrin.
IPR019765. Ephrin_CS.
[Graphical view]

PANTHER

PTHR11304. PTHR11304. 1 hit.

Pfam

PF00812. Ephrin. 1 hit.
[Graphical view]

PRINTS

PR01347. EPHRIN.

ProDom

PD002533. Ephrin. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SUPFAM

SSF49503. Cupredoxin. 1 hit.

PROSITE

PS01299. EPHRIN_RBD_1. 1 hit.
PS51551. EPHRIN_RBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P52799.

GenomeRNAi

1948.

NextBio

7895.

SOURCE

Search...

Entry information

Entry name

EFNB2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.