P52798 (EFNA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ephrin-A4

Alternative name(s):
EPH-related receptor tyrosine kinase ligand 4
Short name=LERK-4

Gene names

Name:	EFNA4
Synonyms:	EPLG4, LERK4

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	201 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. May play a role in the interaction between activated B-lymphocytes and dendritic cells in tonsils.
Subcellular location	Isoform 1: Cell membrane; Lipid-anchor › GPI-anchor. Isoform 2: Secreted Probable.
Tissue specificity	Expressed in the adult spleen, lymph node, prostate, ovary, small intestine, and colon, and in fetal heart, lung, liver and kidney. Also detected in hematopoietic cell lines.
Sequence similarities	Belongs to the ephrin family. Contains 1 ephrin RBD (ephrin receptor-binding) domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell signaling Traceable author statement PubMed 8660976. Source: ProtInc
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement PubMed 8660976. Source: ProtInc
Molecular_function	transmembrane-ephrin receptor activity Traceable author statement PubMed 8660976. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P52798-1)

Also known as: GPI-anchored;

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.

Isoform 2 (identifier: P52798-2)

Also known as: Secreted;

The sequence of this isoform differs from the canonical sequence as follows:
     157-201: KSESAHPVGS...LLILRLLRIL → NLPSHPKEPE...VPIQTDKMEH

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Ref.7
	Chain	26 – 170	145	Ephrin-A4		PRO_0000008373
	Propeptide	171 – 201	31	Removed in mature form Potential		PRO_0000008374
Regions
	Domain	26 – 155	130	Ephrin RBD
Amino acid modifications
	Lipidation	170	1	GPI-anchor amidated serine Potential
	Glycosylation	33	1	N-linked (GlcNAc...) Potential
	Disulfide bond	58 ↔ 99		By similarity
	Disulfide bond	86 ↔ 144		By similarity
Natural variations
	Alternative sequence	157 – 201	45	KSESA…LLRIL → NLPSHPKEPESSQDPLEEEG SLLPALGVPIQTDKMEH in isoform 2.		VSP_001448

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (GPI-anchored) [UniParc]. Last modified October 1, 1996. Version 1. Checksum: ABE8D5443A9AF28D	FASTA	201	22,386
	10 20 30 40 50 60 MRLLPLLRTV LWAAFLGSPL RGGSSLRHVV YWNSSNPRLL RGDAVVELGL NDYLDIVCPH 70 80 90 100 110 120 YEGPGPPEGP ETFALYMVDW PGYESCQAEG PRAYKRWVCS LPFGHVQFSE KIQRFTPFSL 130 140 150 160 170 180 GFEFLPGETY YYISVPTPES SGQCLRLQVS VCCKERKSES AHPVGSPGES GTSGWRGGDT 190 200 PSPLCLLLLL LLLILRLLRI L
	Isoform 2 (Secreted) [UniParc]. Checksum: D0817324CC728EF5	FASTA	193	21,699
	10 20 30 40 50 60 MRLLPLLRTV LWAAFLGSPL RGGSSLRHVV YWNSSNPRLL RGDAVVELGL NDYLDIVCPH 70 80 90 100 110 120 YEGPGPPEGP ETFALYMVDW PGYESCQAEG PRAYKRWVCS LPFGHVQFSE KIQRFTPFSL 130 140 150 160 170 180 GFEFLPGETY YYISVPTPES SGQCLRLQVS VCCKERNLPS HPKEPESSQD PLEEEGSLLP 190 ALGVPIQTDK MEH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Ligands for the receptor tyrosine kinases hek and elk: isolation of cDNAs encoding a family of proteins." Kozlosky C.J., Maraskovsky E., McGrew J.T., Vanden Bos T., Teepe M., Lyman S.D., Srinivasan S., Fletcher F.A., Gayle R.B. III, Cerretti D.P., Beckmann M.P. Oncogene 10:299-306(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"A splice variant of human ephrin-A4 encodes a soluble molecule that is secreted by activated human B lymphocytes." Aasheim H.-C., Munthe E., Funderud S., Smeland E.B., Beiske K., Logtenberg T. Blood 95:221-230(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: B-cell.
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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 1).
[7]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-40.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U14188 mRNA. Translation: AAC50079.1. AJ006352 mRNA. Translation: CAA06992.1. AJ006353 mRNA. Translation: CAA06993.1. CR533569 mRNA. Translation: CAG38600.1. AL691442 Genomic DNA. Translation: CAI15316.1. AL691442 Genomic DNA. Translation: CAI15317.1. CH471121 Genomic DNA. Translation: EAW53139.1. BC107483 mRNA. Translation: AAI07484.1.
IPI	IPI00005125. IPI00942714.
PIR	I38850.
RefSeq	NP_005218.1. NM_005227.2. NP_872632.2. NM_182690.2.
UniGene	Hs.449913. Hs.639422.
3D structure databases
ProteinModelPortal	P52798.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48295N.
IntAct	P52798. 1 interaction.
STRING	9606.ENSP00000403005.
PTM databases
PhosphoSite	P52798.
Polymorphism databases
DMDM	1706672.
Proteomic databases
PaxDb	P52798.
PRIDE	P52798.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000359751; ENSP00000352789; ENSG00000243364. ENST00000368409; ENSP00000357394; ENSG00000243364.
GeneID	1945.
KEGG	hsa:1945.
UCSC	uc001fhc.3. human. uc001fhe.3. human.
Organism-specific databases
CTD	1945.
GeneCards	GC01P155036.
HGNC	HGNC:3224. EFNA4.
HPA	CAB021350.
MIM	601380. gene.
neXtProt	NX_P52798.
Orphanet	35098. Isolated plagiocephaly.
PharmGKB	PA27659.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG266803.
HOGENOM	HOG000234373.
HOVERGEN	HBG051447.
InParanoid	P52798.
KO	K05462.
OMA	CCKESKS.
OrthoDB	EOG45X7X7.
PhylomeDB	P52798.
Gene expression databases
ArrayExpress	P52798.
Bgee	P52798.
CleanEx	HS_EFNA4.
Genevestigator	P52798.
GermOnline	ENSG00000143620. 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
GenomeRNAi	1945.
NextBio	7879.
SOURCE	Search...

Entry information

Entry name

EFNA4_HUMAN

Accession

Primary (citable) accession number: P52798
Secondary accession number(s): C9JHJ8 , O95457, Q5SR71, Q6FI57

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 114 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.