P52803 (EFNA5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin-A5

Alternative name(s):
AL-1
EPH-related receptor tyrosine kinase ligand 7
Short name=LERK-7

Gene names

Name:	EFNA5
Synonyms:	EPLG7, LERK7

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	228 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 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. Ref.4 Ref.5
Subunit structure	Binds to EPHB2. Interacts with EPHA8; activates EPHA8 By similarity. 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. Ref.6
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Membrane › caveola; Lipid-anchor › GPI-anchor. Note: Compartmentalized in discrete caveolae-like membrane microdomains. Ref.5
Sequence similarities	Belongs to the ephrin family. Contains 1 ephrin RBD (ephrin receptor-binding) domain.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Developmental protein
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ephrin receptor signaling pathway Inferred from direct assay Ref.5. Source: UniProtKB nervous system development Traceable author statement Ref.2. Source: ProtInc positive regulation of peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of Rac GTPase activity Inferred from sequence or structural similarity. Source: UniProtKB regulation of actin cytoskeleton organization Inferred from direct assay Ref.5. Source: UniProtKB regulation of cell-cell adhesion Inferred from direct assay Ref.5. Source: UniProtKB regulation of focal adhesion assembly Inferred from direct assay Ref.5. Source: UniProtKB regulation of insulin secretion involved in cellular response to glucose stimulus Inferred from sequence or structural similarity. Source: UniProtKB regulation of microtubule cytoskeleton organization Inferred from direct assay Ref.5. Source: UniProtKB retinal ganglion cell axon guidance Inferred from electronic annotation. Source: Compara
Cellular_component	anchored to external side of plasma membrane Inferred from direct assay Ref.5. Source: UniProtKB caveola Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	chemorepellent activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Chain	21 – 203	183	Ephrin-A5		PRO_0000008377
	Propeptide	204 – 228	25	Removed in mature form Potential		PRO_0000008378
Regions
	Domain	29 – 162	134	Ephrin RBD
Amino acid modifications
	Lipidation	203	1	GPI-anchor amidated asparagine Potential
	Glycosylation	37	1	N-linked (GlcNAc...) Ref.7
	Disulfide bond	62 ↔ 102
	Disulfide bond	90 ↔ 151
Natural variations
	Natural variant	55	1	N → K. Corresponds to variant rs469062 [ dbSNP | Ensembl ].		VAR_012035

Sequences

	Sequence		Length	Mass (Da)
	P52803 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 6893B1CCACFF3F57	FASTA	228	26,297
	10 20 30 40 50 60 MLHVEMLTLV FLVLWMCVFS QDPGSKAVAD RYAVYWNSSN PRFQRGDYHI DVCINDYLDV 70 80 90 100 110 120 FCPHYEDSVP EDKTERYVLY MVNFDGYSAC DHTSKGFKRW ECNRPHSPNG PLKFSEKFQL 130 140 150 160 170 180 FTPFSLGFEF RPGREYFYIS SAIPDNGRRS CLKLKVFVRP TNSCMKTIGV HDRVFDVNDK 190 200 210 220 VENSLEPADD TVHESAEPSR GENAAQTPRI PSRLLAILLF LLAMLLTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of AL-1, a ligand for an Eph-related tyrosine kinase receptor involved in axon bundle formation." Winslow J.W., Moran P., Valverde J., Shih A., Yuan J.Q., Wong S.C., Tsai S.P., Goddard A., Henzel W.J., Hefti F., Beck K.D., Caras I.W. Neuron 14:973-981(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"LERK-7: a ligand of the Eph-related kinases is developmentally regulated in the brain." Kozlosky C.J., Vanden Bos T., Park L.S., Cerretti D.P., Carpenter M.K. Cytokine 9:540-549(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"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: Brain.
[4]	"Compartmentalized signaling by GPI-anchored ephrin-A5 requires the Fyn tyrosine kinase to regulate cellular adhesion." Davy A., Gale N.W., Murray E.W., Klinghoffer R.A., Soriano P., Feuerstein C., Robbins S.M. Genes Dev. 13:3125-3135(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling." Lawrenson I.D., Wimmer-Kleikamp S.H., Lock P., Schoenwaelder S.M., Down M., Boyd A.W., Alewood P.F., Lackmann M. J. Cell Sci. 115:1059-1072(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL-CELL ADHESION, EPHA3-BINDING, SUBCELLULAR LOCATION.
[6]	"Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans." Janes P.W., Saha N., Barton W.A., Kolev M.V., Wimmer-Kleikamp S.H., Nievergall E., Blobel C.P., Himanen J.P., Lackmann M., Nikolov D.B. Cell 123:291-304(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH ADAM10 AND EPHA3.
[7]	"Crystal structure of the human ephrin-A5 ectodomain." Nikolov D.B., Li C., Lackmann M., Jeffrey P., Himanen J.P. Protein Sci. 16:996-1000(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 27-189, GLYCOSYLATION AT ASN-37.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U26403 mRNA. Translation: AAB60377.1.
BC075054 mRNA. Translation: AAH75054.1.
BC075055 mRNA. Translation: AAH75055.1.

IPI

IPI00005517.

PIR

I58170.

RefSeq

NP_001953.1. NM_001962.2.

UniGene

Hs.288741.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2X11	X-ray	4.83	B	27-166	[»]
3MX0	X-ray	3.51	B/D	28-165	[»]

ProteinModelPortal

P52803.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48296N.

IntAct

P52803. 2 interactions.

MINT

MINT-7241704.

STRING

9606.ENSP00000328777.

Polymorphism databases

DMDM

1706678.

Proteomic databases

PaxDb

P52803.

PeptideAtlas

P52803.

PRIDE

P52803.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000333274; ENSP00000328777; ENSG00000184349.

GeneID

1946.

KEGG

hsa:1946.

UCSC

uc003kol.3. human.

Organism-specific databases

CTD

1946.

GeneCards

GC05M106712.

HGNC

HGNC:3225. EFNA5.

HPA

CAB013282.

MIM

601535. gene.

neXtProt

NX_P52803.

PharmGKB

PA27660.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG241965.

HOGENOM

HOG000234373.

HOVERGEN

HBG051447.

InParanoid

P52803.

KO

K05462.

OMA

PANSCMK.

OrthoDB

EOG43N7DK.

PhylomeDB

P52803.

Enzyme and pathway databases

Pathway_Interaction_DB

epha_fwdpathway. EPHA forward signaling.
ephbfwdpathway. EPHB forward signaling.
ephrinarevpathway. Ephrin A reverse signaling.
ephrina_ephapathway. EphrinA-EPHA pathway.

Gene expression databases

ArrayExpress

P52803.

Bgee

P52803.

CleanEx

HS_EFNA5.

Genevestigator

P52803.

GermOnline

ENSG00000184349. 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

P52803.

GenomeRNAi

1946.

NextBio

7887.

SOURCE

Search...

Entry information

Entry name

EFNA5_HUMAN

Accession

Primary (citable) accession number: P52803

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 107 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.