UniProtKB - Q07496 (EPHA4_CHICK)
Protein
Ephrin type-A receptor 4
Gene
EPHA4
Organism
Gallus gallus (Chicken)
Status
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
- EC:2.7.10.1PROSITE-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
- identical protein binding Source: Ensembl
- PH domain binding Source: Ensembl
- protein kinase activity Source: UniProtKB
- protein tyrosine kinase binding Source: Ensembl
- transmembrane-ephrin receptor activity Source: UniProtKB
- transmembrane receptor protein tyrosine kinase activity Source: GO_Central
GO - Biological processi
- adherens junction organization Source: Ensembl
- adult walking behavior Source: Ensembl
- axon guidance Source: GO_Central
- cell adhesion Source: UniProtKB-KW
- cellular response to amyloid-beta Source: Ensembl
- cochlea development Source: Ensembl
- corticospinal tract morphogenesis Source: Ensembl
- fasciculation of motor neuron axon Source: Ensembl
- fasciculation of sensory neuron axon Source: UniProtKB
- motor neuron axon guidance Source: Ensembl
- multicellular organism development Source: GO_Central
- negative regulation of axon regeneration Source: Ensembl
- negative regulation of long-term synaptic potentiation Source: Ensembl
- negative regulation of proteolysis involved in cellular protein catabolic process Source: Ensembl
- nephric duct morphogenesis Source: Ensembl
- peptidyl-tyrosine phosphorylation Source: UniProtKB
- positive regulation of amyloid-beta formation Source: Ensembl
- positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process Source: Ensembl
- positive regulation of JUN kinase activity Source: Ensembl
- positive regulation of kinase activity Source: GO_Central
- positive regulation of protein tyrosine kinase activity Source: Ensembl
- positive regulation of Rho guanyl-nucleotide exchange factor activity Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- protein stabilization Source: Ensembl
- regulation of astrocyte differentiation Source: Ensembl
- regulation of axonogenesis Source: Ensembl
- regulation of dendritic spine morphogenesis Source: Ensembl
- regulation of GTPase activity Source: UniProtKB
- regulation of modification of synaptic structure Source: Ensembl
- segmentation Source: AgBase
- somitogenesis Source: AgBase
- synapse pruning Source: Ensembl
- transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
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 |
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 | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Archelosauria › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galloanserae › Galliformes › Phasianidae › Phasianinae › Gallus |
Proteomesi |
|
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Single-pass type I membrane protein By similarity
Endosome
- Early endosome By similarity
Note: Clustered upon activation and targeted to early endosome.By similarity
Endosome
- early endosome membrane Source: UniProtKB
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- integral component of postsynaptic membrane Source: Ensembl
- integral component of presynaptic membrane Source: Ensembl
- plasma membrane Source: Reactome
Other locations
- axon Source: Ensembl
- cytoplasm Source: UniProtKB
- dendritic spine Source: GO_Central
- glutamatergic synapse Source: Ensembl
- neuron projection Source: GO_Central
- receptor complex Source: GO_Central
- Schaffer collateral - CA1 synapse Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | 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, MembranePTM / 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 | Graphical view | 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, PhosphoproteinProteomic databases
PaxDbi | 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 testis and 13 other tissues |
ExpressionAtlasi | Q07496, baseline and differential |
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 PublicationGO - Molecular functioni
- DH domain binding Source: UniProtKB
- identical protein binding Source: Ensembl
- PH domain binding Source: Ensembl
- protein tyrosine kinase binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 675840, 1 interactor |
STRINGi | 9031.ENSGALP00000008426 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | 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 helixPhylogenomic databases
eggNOGi | KOG0196, Eukaryota |
GeneTreei | ENSGT00940000156948 |
HOGENOMi | CLU_000288_141_1_1 |
InParanoidi | Q07496 |
OMAi | ASCAKCP |
PhylomeDBi | Q07496 |
TreeFami | TF315608 |
Family and domain databases
CDDi | cd10482, EphR_LBD_A4, 1 hit cd00063, FN3, 2 hits cd09545, SAM_EPH-A4, 1 hit |
Gene3Di | 1.10.150.50, 1 hit 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 IPR030602, EphA4_SAM 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 IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom IPR016257, Tyr_kinase_ephrin_rcpt IPR001426, Tyr_kinase_rcpt_V_CS |
Pfami | View protein in Pfam PF14575, EphA2_TM, 1 hit PF01404, Ephrin_lbd, 1 hit PF00041, fn3, 2 hits PF07714, PK_Tyr_Ser-Thr, 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 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, 1 hit |
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 |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
Q07496-1 [UniParc]FASTAAdd to basket
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A1D5PNP7 | A0A1D5PNP7_CHICK | Receptor protein-tyrosine kinase | EPHA4 | 927 | 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 |
RefSeqi | NP_990112.1, NM_204781.1 |
Genome annotation databases
Ensembli | ENSGALT00000008440; ENSGALP00000008426; ENSGALG00000005256 |
GeneIDi | 395559 |
KEGGi | gga:395559 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D38174 mRNA Translation: BAA07373.1 Z19059 mRNA Translation: CAA79509.1 |
PIRi | I50617 |
RefSeqi | NP_990112.1, NM_204781.1 |
3D structure databases
SMRi | Q07496 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 675840, 1 interactor |
STRINGi | 9031.ENSGALP00000008426 |
Proteomic databases
PaxDbi | Q07496 |
Genome annotation databases
Ensembli | ENSGALT00000008440; ENSGALP00000008426; ENSGALG00000005256 |
GeneIDi | 395559 |
KEGGi | gga:395559 |
Organism-specific databases
CTDi | 2043 |
Phylogenomic databases
eggNOGi | KOG0196, Eukaryota |
GeneTreei | ENSGT00940000156948 |
HOGENOMi | CLU_000288_141_1_1 |
InParanoidi | Q07496 |
OMAi | ASCAKCP |
PhylomeDBi | Q07496 |
TreeFami | TF315608 |
Enzyme and pathway databases
BRENDAi | 2.7.10.1, 1306 |
Miscellaneous databases
PROi | PR:Q07496 |
Gene expression databases
Bgeei | ENSGALG00000005256, Expressed in testis and 13 other tissues |
ExpressionAtlasi | Q07496, baseline and differential |
Family and domain databases
CDDi | cd10482, EphR_LBD_A4, 1 hit cd00063, FN3, 2 hits cd09545, SAM_EPH-A4, 1 hit |
Gene3Di | 1.10.150.50, 1 hit 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 IPR030602, EphA4_SAM 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 IPR008266, Tyr_kinase_AS IPR020635, Tyr_kinase_cat_dom IPR016257, Tyr_kinase_ephrin_rcpt IPR001426, Tyr_kinase_rcpt_V_CS |
Pfami | View protein in Pfam PF14575, EphA2_TM, 1 hit PF01404, Ephrin_lbd, 1 hit PF00041, fn3, 2 hits PF07714, PK_Tyr_Ser-Thr, 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 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, 1 hit |
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 |
ProtoNeti | Search... |
MobiDBi | Search... |
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: | April 7, 2021 | |
This is version 185 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
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families