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Protein

Ephrin-A5

Gene

Efna5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cell surface GPI-bound 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. Induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate receptor. This signaling event requires the activity of the Fyn tyrosine kinase. Activates the EPHA3 receptor to regulate cell-cell adhesion and cytoskeletal organization. With the receptor EPHA2 may regulate lens fiber cells shape and interactions and be important for lens transparency maintenance. May function actively to stimulate axon fasciculation. The interaction of EFNA5 with EPHA5 also mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion. Cognate/functional ligand for EPHA7, their interaction regulates brain development modulating cell-cell adhesion and repulsion.4 Publications

GO - Molecular functioni

  • chemorepellent activity Source: MGI
  • ephrin receptor binding Source: UniProtKB
  • neurotrophin TRKB receptor binding Source: BHF-UCL

GO - Biological processi

  • axon guidance Source: MGI
  • cellular response to follicle-stimulating hormone stimulus Source: MGI
  • cellular response to forskolin Source: MGI
  • collateral sprouting Source: BHF-UCL
  • ephrin receptor signaling pathway Source: UniProtKB
  • negative regulation of substrate adhesion-dependent cell spreading Source: MGI
  • positive regulation of collateral sprouting Source: BHF-UCL
  • positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
  • positive regulation of synapse assembly Source: BHF-UCL
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of cell-cell adhesion Source: UniProtKB
  • regulation of cell morphogenesis Source: MGI
  • regulation of focal adhesion assembly Source: UniProtKB
  • regulation of GTPase activity Source: UniProtKB
  • regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
  • regulation of microtubule cytoskeleton organization Source: UniProtKB
  • retinal ganglion cell axon guidance Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis

Enzyme and pathway databases

ReactomeiR-MMU-2682334. EPH-Ephrin signaling.
R-MMU-3928663. EPHA-mediated growth cone collapse.
R-MMU-3928665. EPH-ephrin mediated repulsion of cells.

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin-A5
Alternative name(s):
AL-1
EPH-related receptor tyrosine kinase ligand 7
Short name:
LERK-7
Gene namesi
Name:Efna5
Synonyms:Epl7, Eplg7, Lerk7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:107444. Efna5.

Subcellular locationi

GO - Cellular componenti

  • adherens junction Source: MGI
  • anchored component of external side of plasma membrane Source: UniProtKB
  • anchored component of plasma membrane Source: GO_Central
  • basement membrane Source: MGI
  • caveola Source: UniProtKB-SubCell
  • cell periphery Source: MGI
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice display cataract an opacification of the lens.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence analysisAdd
BLAST
Chaini21 – 203183Ephrin-A5PRO_0000008379Add
BLAST
Propeptidei204 – 22825Removed in mature formSequence analysisPRO_0000008380Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi37 – 371N-linked (GlcNAc...)1 Publication
Disulfide bondi62 ↔ 102PROSITE-ProRule annotation1 Publication
Disulfide bondi90 ↔ 151PROSITE-ProRule annotation1 Publication
Glycosylationi162 – 1621N-linked (GlcNAc...); atypical1 Publication
Lipidationi203 – 2031GPI-anchor amidated asparagineSequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

MaxQBiO08543.
PaxDbiO08543.
PRIDEiO08543.

Expressioni

Gene expression databases

BgeeiO08543.
CleanExiMM_EFNA5.
GenevisibleiO08543. MM.

Interactioni

Subunit structurei

Binds to the receptor tyrosine kinases EPHA2, EPHA3 and EPHB1. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function (By similarity). Binds to EPHB2. Interacts with EPHA8; activates EPHA8.By similarity2 Publications

GO - Molecular functioni

  • ephrin receptor binding Source: UniProtKB
  • neurotrophin TRKB receptor binding Source: BHF-UCL

Protein-protein interaction databases

IntActiO08543. 2 interactions.
STRINGi10090.ENSMUSP00000076115.

Structurei

Secondary structure

1
228
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi30 – 356Combined sources
Helixi41 – 444Combined sources
Beta strandi49 – 524Combined sources
Beta strandi57 – 615Combined sources
Beta strandi67 – 693Combined sources
Beta strandi71 – 733Combined sources
Beta strandi77 – 826Combined sources
Helixi84 – 885Combined sources
Beta strandi92 – 10211Combined sources
Beta strandi108 – 1114Combined sources
Beta strandi113 – 1175Combined sources
Beta strandi134 – 14411Combined sources
Beta strandi148 – 1503Combined sources
Beta strandi153 – 1586Combined sources
Turni161 – 1644Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1SHWX-ray2.20A28-164[»]
1SHXX-ray2.10A/B28-164[»]
ProteinModelPortaliO08543.
SMRiO08543. Positions 28-165.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO08543.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 162134Ephrin RBDPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3858. Eukaryota.
ENOG4111FMJ. LUCA.
GeneTreeiENSGT00390000015107.
HOGENOMiHOG000234373.
HOVERGENiHBG051447.
InParanoidiO08543.
KOiK05462.
OMAiTERYILY.
OrthoDBiEOG70W3FD.
PhylomeDBiO08543.

Family and domain databases

Gene3Di2.60.40.420. 1 hit.
InterProiIPR008972. Cupredoxin.
IPR031328. Ephrin.
IPR019765. Ephrin_CS.
IPR001799. Ephrin_RBD.
[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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: O08543-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLHVEMLTLL FLVLWMCVFS QDPGSKVVAD RYAVYWNSSN PRFQRGDYHI
60 70 80 90 100
DVCINDYLDV FCPHYEDSVP EDKTERYVLY MVNFDGYSAC DHTSKGFKRW
110 120 130 140 150
ECNRPHSPNG PLKFSEKFQL FTPFSLGFEF RPGREYFYIS SAIPDNGRRS
160 170 180 190 200
CLKLKVFVRP TNSCMKTIGV HDRVFDVNDK VENSLEPADD TVHESAEPSR
210 220
GENAAQTPRI PSRLLAILLF LLAMLLTL
Length:228
Mass (Da):26,339
Last modified:July 1, 1997 - v1
Checksum:i85439F5337420022
GO
Isoform Short (identifier: O08543-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     163-189: Missing.

Show »
Length:201
Mass (Da):23,338
Checksum:iC5F5E78FD6674316
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei163 – 18927Missing in isoform Short. 1 PublicationVSP_001449Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U90664 mRNA. Translation: AAB50239.1.
U90665 mRNA. Translation: AAB50240.1.
BC040218 mRNA. Translation: AAH40218.1.
CCDSiCCDS28934.1. [O08543-2]
CCDS28935.1. [O08543-1]
RefSeqiNP_034239.1. NM_010109.3. [O08543-2]
NP_997537.1. NM_207654.2. [O08543-1]
UniGeneiMm.401670.
Mm.7978.

Genome annotation databases

EnsembliENSMUST00000076840; ENSMUSP00000076115; ENSMUSG00000048915. [O08543-1]
ENSMUST00000078839; ENSMUSP00000077883; ENSMUSG00000048915. [O08543-2]
GeneIDi13640.
KEGGimmu:13640.
UCSCiuc008dfg.2. mouse. [O08543-1]
uc008dfh.2. mouse. [O08543-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U90664 mRNA. Translation: AAB50239.1.
U90665 mRNA. Translation: AAB50240.1.
BC040218 mRNA. Translation: AAH40218.1.
CCDSiCCDS28934.1. [O08543-2]
CCDS28935.1. [O08543-1]
RefSeqiNP_034239.1. NM_010109.3. [O08543-2]
NP_997537.1. NM_207654.2. [O08543-1]
UniGeneiMm.401670.
Mm.7978.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1SHWX-ray2.20A28-164[»]
1SHXX-ray2.10A/B28-164[»]
ProteinModelPortaliO08543.
SMRiO08543. Positions 28-165.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO08543. 2 interactions.
STRINGi10090.ENSMUSP00000076115.

Proteomic databases

MaxQBiO08543.
PaxDbiO08543.
PRIDEiO08543.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000076840; ENSMUSP00000076115; ENSMUSG00000048915. [O08543-1]
ENSMUST00000078839; ENSMUSP00000077883; ENSMUSG00000048915. [O08543-2]
GeneIDi13640.
KEGGimmu:13640.
UCSCiuc008dfg.2. mouse. [O08543-1]
uc008dfh.2. mouse. [O08543-2]

Organism-specific databases

CTDi1946.
MGIiMGI:107444. Efna5.

Phylogenomic databases

eggNOGiKOG3858. Eukaryota.
ENOG4111FMJ. LUCA.
GeneTreeiENSGT00390000015107.
HOGENOMiHOG000234373.
HOVERGENiHBG051447.
InParanoidiO08543.
KOiK05462.
OMAiTERYILY.
OrthoDBiEOG70W3FD.
PhylomeDBiO08543.

Enzyme and pathway databases

ReactomeiR-MMU-2682334. EPH-Ephrin signaling.
R-MMU-3928663. EPHA-mediated growth cone collapse.
R-MMU-3928665. EPH-ephrin mediated repulsion of cells.

Miscellaneous databases

ChiTaRSiEfna5. mouse.
EvolutionaryTraceiO08543.
PROiO08543.
SOURCEiSearch...

Gene expression databases

BgeeiO08543.
CleanExiMM_EFNA5.
GenevisibleiO08543. MM.

Family and domain databases

Gene3Di2.60.40.420. 1 hit.
InterProiIPR008972. Cupredoxin.
IPR031328. Ephrin.
IPR019765. Ephrin_CS.
IPR001799. Ephrin_RBD.
[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. "Distinct and overlapping expression patterns of ligands for Eph-related receptor tyrosine kinases during mouse embryogenesis."
    Flenniken A.M., Gale N.W., Yancopoulos G.D., Wilkinson D.G.
    Dev. Biol. 179:382-401(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
  2. "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] (ISOFORM LONG).
    Strain: FVB/N.
    Tissue: Mammary gland.
  3. "The Eek receptor, a member of the Eph family of tyrosine protein kinases, can be activated by three different Eph family ligands."
    Park S., Sanchez M.P.
    Oncogene 14:533-542(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN EPHA8 ACTIVATION, INTERACTION WITH EPHA8.
  4. "Regulation of repulsion versus adhesion by different splice forms of an Eph receptor."
    Holmberg J., Clarke D.L., Frisen J.
    Nature 408:203-206(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL ADHESION AND REPULSION, EPHA7 RECEPTOR-BINDING.
  5. "EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets."
    Konstantinova I., Nikolova G., Ohara-Imaizumi M., Meda P., Kucera T., Zarbalis K., Wurst W., Nagamatsu S., Lammert E.
    Cell 129:359-370(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN INSULIN SECRETION.
  6. "Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract."
    Cooper M.A., Son A.I., Komlos D., Sun Y., Kleiman N.J., Zhou R.
    Proc. Natl. Acad. Sci. U.S.A. 105:16620-16625(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION IN LENS FIBER CELLS MORPHOGENESIS.
  7. "The mouse C2C12 myoblast cell surface N-linked glycoproteome: identification, glycosite occupancy, and membrane orientation."
    Gundry R.L., Raginski K., Tarasova Y., Tchernyshyov I., Bausch-Fluck D., Elliott S.T., Boheler K.R., Van Eyk J.E., Wollscheid B.
    Mol. Cell. Proteomics 8:2555-2569(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-162.
    Tissue: Myoblast.
  8. "Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling."
    Himanen J.P., Chumley M.J., Lackmann M., Li C., Barton W.A., Jeffrey P.D., Vearing C., Geleick D., Feldheim D.A., Boyd A.W., Henkemeyer M., Nikolov D.B.
    Nat. Neurosci. 7:501-509(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 28-165 ALONE AND IN COMPLEX WITH EPHB2, GLYCOSYLATION AT ASN-37, DISULFIDE BONDS.

Entry informationi

Entry nameiEFNA5_MOUSE
AccessioniPrimary (citable) accession number: O08543
Secondary accession number(s): O08544
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: July 6, 2016
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.