EPHA4

Functionⁱ

Receptor tyrosine kinase which binds membrane-bound ephrin family ligands 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. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections (By similarity).By similarity

Catalytic activityⁱ

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	653	ATPPROSITE-ProRule annotation		1
Active siteⁱ	746	Proton acceptorPROSITE-ProRule annotation		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	627 – 635	ATPPROSITE-ProRule annotation		9

GO - Molecular functionⁱ

ATP binding Source: UniProtKB-KW
DH domain binding Source: UniProtKB
GPI-linked ephrin receptor activity Source: UniProtKB
protein kinase activity Source: UniProtKB
transmembrane-ephrin receptor activity Source: UniProtKB

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

cell adhesion Source: UniProtKB-KW
fasciculation of sensory neuron axon Source: UniProtKB
peptidyl-tyrosine phosphorylation Source: UniProtKB
positive regulation of Rho guanyl-nucleotide exchange factor activity Source: UniProtKB
protein autophosphorylation Source: UniProtKB
regulation of GTPase activity Source: UniProtKB
segmentation
Source: AgBase
Non-traceable author statementⁱ
- 12617855
- 14516678
somitogenesis
Source: AgBase
Non-traceable author statementⁱ
- 12617855
- 14516678

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological process	Cell adhesion, Neurogenesis
Ligand	ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	2.7.10.1 1306

BRENDAⁱ

2.7.10.1 1306

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Ephrin type-A receptor 4 (EC:2.7.10.1) Alternative name(s): EPH-like kinase 8 Short name: EK8 Short name: cEK8
Gene namesⁱ	Name:EPHA4 Synonyms:CEK8
Organismⁱ	Gallus gallus (Chicken)
Taxonomic identifierⁱ	9031 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Sauropsida › Sauria › Archelosauria › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galloanserae › Galliformes › Phasianidae › Phasianinae › Gallus
Proteomesⁱ	UP000000539 Componentⁱ: Unplaced

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	20 – 547	ExtracellularSequence analysisAdd BLAST	528
Transmembraneⁱ	548 – 569	HelicalSequence analysisAdd BLAST	22
Topological domainⁱ	570 – 986	CytoplasmicSequence analysisAdd BLAST	417

Keywords - Cellular componentⁱ

Cell membrane, Endosome, Membrane

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 19	Sequence analysisAdd BLAST		19
ChainⁱPRO_0000016809	20 – 986	Ephrin type-A receptor 4Add BLAST		967

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Glycosylationⁱ	235	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	340	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	408	N-linked (GlcNAc...) asparagineSequence analysis	1
Modified residueⁱ	596	Phosphotyrosine; by autocatalysisBy similarity	1
Modified residueⁱ	602	Phosphotyrosine; by autocatalysisBy similarity	1
Modified residueⁱ	779	Phosphotyrosine; by autocatalysisSequence analysis	1
Modified residueⁱ	928	Phosphotyrosine; by autocatalysisSequence analysis	1

Keywords - PTMⁱ

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbⁱ	Q07496
PRIDEⁱ	Q07496

Expressionⁱ

Tissue specificityⁱ

Expressed at high levels in brain, with expression also detected in the kidney, lung, muscle and thymus.

Gene expression databases

Bgeeⁱ	ENSGALG00000005256 Expressed in 11 organ(s), highest expression level in testis

Bgeeⁱ

ENSGALG00000005256 Expressed in 11 organ(s), highest expression level in testis

Interactionⁱ

Subunit structureⁱ

Interacts with the src family kinase, p59-Fyn, through the major phosphorylation site at position Tyr-602 (By similarity). Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases.By similarity1 Publication

GO - Molecular functionⁱ

DH domain binding Source: UniProtKB

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

STRINGⁱ	9031.ENSGALP00000008426

STRINGⁱ

9031.ENSGALP00000008426

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q07496
SMRⁱ	Q07496
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Domainⁱ	30 – 209	Eph LBDPROSITE-ProRule annotationAdd BLAST	180
Domainⁱ	328 – 439	Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST	112
Domainⁱ	440 – 537	Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST	98
Domainⁱ	621 – 882	Protein kinasePROSITE-ProRule annotationAdd BLAST	262
Domainⁱ	911 – 975	SAMPROSITE-ProRule annotationAdd BLAST	65

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	984 – 986	PDZ-bindingSequence analysis		3

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	191 – 325	Cys-richAdd BLAST		135

Sequence similaritiesⁱ

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domainⁱ

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG0196 Eukaryota COG0515 LUCA
HOGENOMⁱ	HOG000233856
HOVERGENⁱ	HBG062180
InParanoidⁱ	Q07496
KEGG Orthology (KO) More...KOⁱ	K05105
OMAⁱ	NGECQAC
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G00W0
PhylomeDBⁱ	Q07496
TreeFamⁱ	TF315608

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd10482 EphR_LBD_A4, 1 hit cd00063 FN3, 2 hits
Gene3Dⁱ	2.60.120.260, 1 hit 2.60.40.10, 2 hits
InterProⁱ	View protein in InterPro IPR027936 Eph_TM IPR034270 EphA4_rcpt_lig-bd IPR001090 Ephrin_rcpt_lig-bd_dom IPR003961 FN3_dom IPR036116 FN3_sf IPR008979 Galactose-bd-like_sf IPR009030 Growth_fac_rcpt_cys_sf IPR013783 Ig-like_fold IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR001660 SAM IPR013761 SAM/pointed_sf IPR001245 Ser-Thr/Tyr_kinase_cat_dom IPR011641 Tyr-kin_ephrin_A/B_rcpt-like IPR008266 Tyr_kinase_AS IPR020635 Tyr_kinase_cat_dom IPR016257 Tyr_kinase_ephrin_rcpt IPR001426 Tyr_kinase_rcpt_V_CS
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF14575 EphA2_TM, 1 hit PF01404 Ephrin_lbd, 1 hit PF00041 fn3, 2 hits PF07714 Pkinase_Tyr, 1 hit PF07647 SAM_2, 1 hit
PIRSFⁱ	PIRSF000666 TyrPK_ephrin_receptor, 1 hit
PRINTSⁱ	PR00109 TYRKINASE
SMARTⁱ	View protein in SMART SM00615 EPH_lbd, 1 hit SM01411 Ephrin_rec_like, 1 hit SM00060 FN3, 2 hits SM00220 S_TKc, 1 hit SM00454 SAM, 1 hit SM00219 TyrKc, 1 hit
SUPFAMⁱ	SSF47769 SSF47769, 1 hit SSF49265 SSF49265, 1 hit SSF49785 SSF49785, 1 hit SSF56112 SSF56112, 1 hit SSF57184 SSF57184, 2 hits
PROSITEⁱ	View protein in PROSITE PS01186 EGF_2, 1 hit PS51550 EPH_LBD, 1 hit PS50853 FN3, 2 hits PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00109 PROTEIN_KINASE_TYR, 1 hit PS00790 RECEPTOR_TYR_KIN_V_1, 1 hit PS00791 RECEPTOR_TYR_KIN_V_2, 1 hit PS50105 SAM_DOMAIN, 1 hit

Sequence (1+)ⁱ

Sequence statusⁱ: Complete.

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

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.ⁱShow all

Q07496-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MAGVPVGALL PLLVGVCGAV TGSRVYPANE VTLLDSRSVQ GELGWIASPL 
        60         70         80         90        100
EGGWEEVSIM DEKNTPIRTY QVCNVMEPSQ NNWLRTDWIP REGAQRVYIE 
       110        120        130        140        150
IKFTLRDCNS LPGVMGTCKE TFNLYYYESN NDKERFIRES QFAKIDTIAA 
       160        170        180        190        200
DESFTQVDIG DRIMKLNTEV RDVGPLSKKG FYLAFQDVGA CIALVSVRVF 
       210        220        230        240        250
YKKCPLTVRN LAQFPDTITG ADTSSLVEVR GSCVNNSEEK DVPKMYCGAD 
       260        270        280        290        300
GEWLVPIGNC LCNAGYEERN GECQACKIGY YKALSTDVAC AKCPPHSYSI 
       310        320        330        340        350
WEGSTSCTCD RGFFRAENDA ASMPCTRPPS APQNLISNVN ETSVNLEWSA 
       360        370        380        390        400
PQNKGGRDDI SYNVVCKRCG AGEPSHCRSC GSGVHFSPQQ NGLKTTKVSI 
       410        420        430        440        450
TDLLAHTNYT FEVWAVNGVS KHNPSQDQAV SVTVTTNQAA PSPIALIQAK 
       460        470        480        490        500
EITRHSVALA WLEPDRPNGV ILEYEVKYYE KDQNERSYRI VKTASRNTDI 
       510        520        530        540        550
KGLNPLTSYV FHVRARTAAG YGDFSGPFEF TTNTVPSPII GDGTNPTVLL 
       560        570        580        590        600
VSVAGSVVLV VILIAAFVIS RRRSKYSKAK QEADEEKHLN QGVRTYVDPF 
       610        620        630        640        650
TYEDPNQAVR EFAKEIDASC IKIEKVIGVG EFGEVCSGRL KVPGKREICV 
       660        670        680        690        700
AIKTLKAGYT DKQRRDFLSE ASIMGQFDHP NIIHLEGVVT KCKPVMIITE 
       710        720        730        740        750
YMENGSLDAF LRKNDGRFTV IQLVGMLRGI GSGMKYLSDM SYVHRDLAAR 
       760        770        780        790        800
NILVNSNLVC KVSDFGMSRV LEDDPEAAYT TRGGKIPIRW TAPEAIAYRK 
       810        820        830        840        850
FTSASDVWSY GIVMWEVMSY GERPYWDMSN QDVIKAIEEG YRLPPPMDCP 
       860        870        880        890        900
IALHQLMLDC WQKERSDRPK FGQIVNMLDK LIRNPNSLKR TGSESSRPST 
       910        920        930        940        950
ALLDPSSPEF SAVVSVSDWL QAIKMERYKD NFTAAGYTTL EAVVHMNQDD 
       960        970        980 
LARIGITAIT HQNKILSSVQ AMRSQMQQMH GRMVPV

Length:986

Mass (Da):109,483

Last modified:November 1, 1997 - v2

Checksum:ⁱBD88C2A5BD840A0F

GO

Computationally mapped potential isoform sequencesⁱ

There are 3 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation
A0A1I7Q3Z3	A0A1I7Q3Z3_CHICK	Ephrin type-A receptor 4 Ephrin type-A receptor 4	EPHA4	1,006	Annotation score:
A0A1D5PNP7	A0A1D5PNP7_CHICK	Ephrin type-A receptor 4 Ephrin type-A receptor 4	EPHA4	927	Annotation score:
A0A1D5PWC7	A0A1D5PWC7_CHICK	Ephrin type-A receptor 4 Ephrin type-A receptor 4	EPHA4	994	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	138	R → G in CAA79509 (PubMed:8510926).Curated		1
Sequence conflictⁱ	487	S → T in CAA79509 (PubMed:8510926).Curated		1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	D38174 mRNA Translation: BAA07373.1 Z19059 mRNA Translation: CAA79509.1
PIRⁱ	I50617
NCBI Reference Sequences More...RefSeqⁱ	NP_990112.1, NM_204781.1
UniGeneⁱ	Gga.304

Genome annotation databases

GeneIDⁱ	395559
KEGGⁱ	gga:395559

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q07496	Ephrin type-A receptor 4		CHICK		1006	UniRef100_Q07496
Ephrin type-A receptor 4		CHICK		927
UPI000739DFCB		CHICK		992

Protein	Similar proteins		Species	Score	Length	Source
Q07496	Ephrin type-A receptor 4	)	MOUSE		986	UniRef90_Q03137
Ephrin type-A receptor 4	)	HUMAN		986
Uncharacterized protein		ALLMI		1042
Ephrin type-A receptor 4		Patagioenas fasciata monilis		1023
Ephrin type-A receptor 4		Bengalese finch		1011
+247

Protein	Similar proteins		Species	Score	Length	Source
Q07496	Ephrin type-A receptor 4	)	MOUSE		986	UniRef50_Q03137
Ephrin type-A receptor 4	)	HUMAN		986
Uncharacterized protein		ALLMI		1042
Ephrin type-A receptor 4		Patagioenas fasciata monilis		1023
Ephrin type-A receptor 4		Bengalese finch		1011
+276

Entry informationⁱ

Entry nameⁱ	EPHA4_CHICK
Accessionⁱ	Q07496Primary (citable) accession number: Q07496 Secondary accession number(s): Q90772
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
	Last sequence update:	November 1, 1997
	Last modified:	September 12, 2018
	This is version 166 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q07496 (EPHA4_CHICK)

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Ephrin type-A receptor 4

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Endosome

Plasma membrane

Endosome

Plasma Membrane

Other locations

Topology

Keywords - Cellular componenti

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Motif

Compositional bias

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Computationally mapped potential isoform sequencesi

Experimental Info

Sequence databases

Genome annotation databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Computationally mapped potential isoform sequencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ