P52800 (EFNB2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin-B2

Alternative name(s):
ELF-2
EPH-related receptor tyrosine kinase ligand 5
Short name=LERK-5
HTK ligand
Short name=HTK-L

Gene names

Name:	Efnb2
Synonyms:	Elf2, Epl5, Eplg5, Htkl, Lerk5

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	336 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.5
Subunit structure	Interacts with PDZRN3. Binds to the ephrin receptor EPHA3, EPHA4 and EPHB4 By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Expressed on lateral floor plate cells, specifically on commissural axon segments that have passed through the floor plate. Expressed in cells of the retinal ganglion cell layer during retinal axon guidance to the optic disk.
Developmental stage	Expressed in the floor plate throughout the period of commissural axon pathfinding.
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.
Sequence caution	The sequence AAC42052.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Angiogenesis Differentiation 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	Notch signaling pathway Inferred from direct assay. Source: BHF-UCL cell adhesion Inferred from sequence or structural similarity. Source: UniProtKB cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW cell migration involved in sprouting angiogenesis Inferred from sequence or structural similarity. Source: UniProtKB ephrin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB lymph vessel development Inferred from mutant phenotype. Source: MGI nervous system development Inferred from electronic annotation. Source: UniProtKB-KW organ morphogenesis Inferred from mutant phenotype. Source: MGI regulation of chemotaxis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay. Source: MGI
Molecular function	receptor binding Inferred from physical interaction Ref.7. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Epha4	Q03137	2	EBI-1032676,EBI-1539152

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 28

28

Potential

Chain

29 – 336

308

Ephrin-B2

PRO_0000008393

Regions

Topological domain

29 – 232

204

Extracellular Potential

Transmembrane

233 – 253

21

Helical; Potential

Topological domain

254 – 336

83

Cytoplasmic Potential

Domain

31 – 167

137

Ephrin RBD

Motif

334 – 336

3

PDZ-binding Potential

Amino acid modifications

Modified residue

307

1

Phosphotyrosine By similarity

Modified residue

314

1

Phosphotyrosine By similarity

Modified residue

319

1

Phosphotyrosine By similarity

Modified residue

328

1

Phosphoserine By similarity

Modified residue

333

1

Phosphotyrosine By similarity

Glycosylation

39

1

N-linked (GlcNAc...)

Glycosylation

142

1

N-linked (GlcNAc...) Potential

Disulfide bond

65 ↔ 104

Disulfide bond

92 ↔ 156

Experimental info

Sequence conflict

177

1

A → T in AAA99708. Ref.1

Secondary structure

1

.

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336

Helix Strand Turn

Details...

Turn

47 – 49

3

Beta strand

50 – 53

4

Beta strand

60 – 64

5

Beta strand

70 – 72

3

Beta strand

78 – 84

7

Helix

86 – 91

6

Beta strand

101 – 104

4

Beta strand

112 – 116

5

Beta strand

133 – 138

6

Helix

145 – 147

3

Helix

154 – 158

5

Beta strand

162 – 167

6

Sequences

	Sequence		Length	Mass (Da)
	P52800 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: D08894996E399554	FASTA	336	37,202
	10 20 30 40 50 60 MAMARSRRDS VWKYCWGLLM VLCRTAISRS IVLEPIYWNS SNSKFLPGQG LVLYPQIGDK 70 80 90 100 110 120 LDIICPKVDS KTVGQYEYYK VYMVDKDQAD RCTIKKENTP LLNCARPDQD VKFTIKFQEF 130 140 150 160 170 180 SPNLWGLEFQ KNKDYYIIST SNGSLEGLDN QEGGVCQTRA MKILMKVGQD ASSAGSARNH 190 200 210 220 230 240 GPTRRPELEA GTNGRSSTTS PFVKPNPGSS TDGNSAGHSG NNLLGSEVAL FAGIASGCII 250 260 270 280 290 300 FIVIIITLVV LLLKYRRRHR KHSPQHTTTL SLSTLATPKR GGNNNGSEPS DVIIPLRTAD 310 320 330 SVFCPHYEKV SGDYGHPVYI VQEMPPQSPA NIYYKV

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: 8559144] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[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: 7534404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: CB57BL/6J X SJL/J.
[3]	"ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites." Bergemann A.D., Cheng H.J., Brambilla R., Klein R., Flanagan J.G. Mol. Cell. Biol. 15:4921-4929(1995) [PubMed: 7651410] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: ICR. Tissue: Brain.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6. Tissue: Brain.
[5]	"Complementary expression of transmembrane ephrins and their receptors in the mouse spinal cord: a possible role in constraining the orientation of longitudinally projecting axons." Imondi R., Wideman C., Kaprielian Z. Development 127:1397-1410(2000) [PubMed: 10704386] [Abstract] Cited for: FUNCTION.
[6]	"Crystal structure of an ephrin ectodomain." Toth J., Cutforth T., Gelinas A.D., Bethoney K.A., Bard J., Harrison C.J. Dev. Cell 1:83-92(2001) [PubMed: 11703926] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 30-170.
[7]	"Crystal structure of an Eph receptor-ephrin complex." Himanen J.-P., Rajashankar K.R., Lackmann M., Cowan C.A., Henkemeyer M., Nikolov D.B. Nature 414:933-938(2001) [PubMed: 11780069] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 31-168 IN COMPLEX WITH EPHB2.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U16819 mRNA. Translation: AAA99708.1.
L38847 mRNA. Translation: AAC42052.1. Different initiation.
U30244 mRNA. Translation: AAA82934.1.
BC057009 mRNA. Translation: AAH57009.1.

IPI

IPI00762720.

PIR

I49766.

RefSeq

NP_034241.2. NM_010111.5.

UniGene

Mm.209813.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IKO	X-ray	1.92	P	30-207	[»]
1KGY	X-ray	2.70	E/F/G/H	31-168	[»]

ProteinModelPortal

P52800.

SMR

P52800. Positions 30-170.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29208N.

IntAct

P52800. 2 interactions.

MINT

MINT-1959060.

STRING

P52800.

PTM databases

PhosphoSite

P52800.

Proteomic databases

PRIDE

P52800.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000001319; ENSMUSP00000001319; ENSMUSG00000001300.

GeneID

13642.

KEGG

mmu:13642.

Organism-specific databases

CTD

1948.

MGI

MGI:105097. Efnb2.

Phylogenomic databases

eggNOG

roNOG10301.

HOVERGEN

HBG051448.

OrthoDB

EOG402WSK.

PhylomeDB

P52800.

Gene expression databases

ArrayExpress

P52800.

Bgee

P52800.

CleanEx

MM_EFNB2.
MM_ELF2.

Genevestigator

P52800.

GermOnline

ENSMUSG00000001300. Mus musculus.

Family and domain databases

InterPro

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

Gene3D

G3DSA:2.60.40.420. Cupredoxin. 1 hit.

KO

K05463.

PANTHER

PTHR11304. Ephrin. 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

NextBio

284346.

SOURCE

Search...

Entry information

Entry name

EFNB2_MOUSE

Accession

Primary (citable) accession number: P52800

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	December 14, 2011
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program