O43921 (EFNA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin-A2

Alternative name(s):
EPH-related receptor tyrosine kinase ligand 6
Short name=LERK-6
HEK7 ligand
Short name=HEK7-L

Gene names

Name:	EFNA2
Synonyms:	EPLG6, LERK6

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	213 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. With the EPHA2 receptor may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis By similarity.
Subunit structure	Binds to the receptor tyrosine kinases EPHA3, EPHA4 and EPHA5. Interacts with EPHA8; activates EPHA8. Ref.4
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor Potential.
Sequence similarities	Belongs to the ephrin family. Contains 1 ephrin RBD (ephrin receptor-binding) domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Domain	Signal
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bone remodeling Inferred from sequence or structural similarity. Source: UniProtKB cell-cell signaling Traceable author statement Ref.2. Source: ProtInc ephrin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB osteoclast differentiation Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ephrin receptor binding Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Potential

Chain

25 – 188

164

Ephrin-A2

PRO_0000008361

Propeptide

189 – 213

25

Removed in mature form Potential

PRO_0000008362

Regions

Domain

34 – 174

141

Ephrin RBD

Amino acid modifications

Lipidation

188

1

GPI-anchor amidated asparagine Potential

Glycosylation

42

1

N-linked (GlcNAc...) Potential

Glycosylation

174

1

N-linked (GlcNAc...) Potential

Glycosylation

188

1

N-linked (GlcNAc...) Potential

Disulfide bond

73 ↔ 114

Ref.4

Disulfide bond

102 ↔ 163

Ref.4

Experimental info

Sequence conflict

6

1

R → A in CAA07435. Ref.2

Sequence conflict

25 – 26

2

RA → PP in CAA07435. Ref.2

Sequence conflict

29 – 30

2

AA → RR in CAA07435. Ref.2

Secondary structure

1

.

.

.

.

.

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.

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.

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.

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213

Helix Strand Turn

Details...

Beta strand

36 – 40

5

Beta strand

51 – 53

3

Beta strand

59 – 63

5

Beta strand

68 – 72

5

Helix

83 – 85

3

Beta strand

89 – 94

6

Helix

96 – 101

6

Beta strand

107 – 114

8

Beta strand

125 – 129

5

Beta strand

147 – 153

7

Beta strand

165 – 170

6

Sequences

	Sequence		Length	Mass (Da)
	O43921 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 33C9FB1A8168B2D0	FASTA	213	23,878
	10 20 30 40 50 60 MAPAQRPLLP LLLLLLPLPP PPFARAEDAA RANSDRYAVY WNRSNPRFHA GAGDDGGGYT 70 80 90 100 110 120 VEVSINDYLD IYCPHYGAPL PPAERMEHYV LYMVNGEGHA SCDHRQRGFK RWECNRPAAP 130 140 150 160 170 180 GGPLKFSEKF QLFTPFSLGF EFRPGHEYYY ISATPPNAVD RPCLRLKVYV RPTNETLYEA 190 200 210 PEPIFTSNNS CSSPGGCRLF LSTIPVLWTL LGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of the genes for mouse LERK-3/Ephrin-A3 (Epl3), mouse LERK-4/Ephrin-A4 (Epl4), and human LERK-6/Ephrin-A2 (EPLG6): conservation of intron/exon structure." Cerretti D.P., Nelson N. Genomics 47:131-135(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Cloning, chromosomal mapping, and tissue expression of the gene encoding the human Eph-family kinase ligand ephrin-A2." Aasheim H.-C., Pedeutour F., Grosgeorge J., Logtenberg T. Biochem. Biophys. Res. Commun. 252:378-382(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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 (2.35 ANGSTROMS) OF 33-177 IN COMPLEX WITH EPHA4, DISULFIDE BONDS, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U92896, U92893, U92894 Genomic DNA. Translation: AAC39577.1.
AJ007292 mRNA. Translation: CAA07435.1.
AC004258 Genomic DNA. Translation: AAC04896.1.

IPI

IPI00015159.

PIR

JE0322.

RefSeq

NP_001396.2. NM_001405.3.

UniGene

Hs.741510.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WO3	X-ray	2.35	B	33-173	[»]

ProteinModelPortal

O43921.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48293N.

MINT

MINT-7013470.

STRING

9606.ENSP00000215368.

PTM databases

PhosphoSite

O43921.

Proteomic databases

PaxDb

O43921.

PRIDE

O43921.

Protocols and materials databases

DNASU

1943.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000215368; ENSP00000215368; ENSG00000099617.

GeneID

1943.

KEGG

hsa:1943.

UCSC

uc002lry.2. human.

Organism-specific databases

CTD

1943.

GeneCards

GC19P001286.

HGNC

HGNC:3222. EFNA2.

HPA

CAB005178.

MIM

602756. gene.

neXtProt

NX_O43921.

PharmGKB

PA27657.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG252953.

HOGENOM

HOG000234373.

HOVERGEN

HBG051447.

InParanoid

O43921.

KO

K05462.

OMA

KVYVRPT.

OrthoDB

EOG43N7DN.

PhylomeDB

O43921.

Enzyme and pathway databases

Pathway_Interaction_DB

epha_fwdpathway. EPHA forward signaling.

Gene expression databases

ArrayExpress

O43921.

Bgee

O43921.

CleanEx

HS_EFNA2.

Genevestigator

O43921.

GermOnline

ENSG00000099617. 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

ChEMBL

CHEMBL1795109.

EvolutionaryTrace

O43921.

GenomeRNAi

1943.

NextBio

7871.

PMAP-CutDB

O43921.

SOURCE

Search...

Entry information

Entry name

EFNA2_HUMAN

Accession

Primary (citable) accession number: O43921
Secondary accession number(s): O76020

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	June 1, 1998
Last modified:	May 1, 2013
This is version 100 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.