Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Ephrin type-A receptor 8

Gene

Epha8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A 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. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system plays also a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth.6 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei666ATPPROSITE-ProRule annotation1
Active sitei759Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi640 – 648ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processCell adhesion, Neurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 3474
ReactomeiR-MMU-2682334 EPH-Ephrin signaling
R-MMU-3928663 EPHA-mediated growth cone collapse
R-MMU-3928665 EPH-ephrin mediated repulsion of cells

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 8 (EC:2.7.10.1)
Alternative name(s):
EPH- and ELK-related kinase
Tyrosine-protein kinase receptor EEK
Gene namesi
Name:Epha8
Synonyms:Eek
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:109378 Epha8

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini27 – 541ExtracellularSequence analysisAdd BLAST515
Transmembranei542 – 562HelicalSequence analysisAdd BLAST21
Topological domaini563 – 1004CytoplasmicSequence analysisAdd BLAST442

Keywords - Cellular componenti

Cell membrane, Cell projection, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi615Y → F: Reduced phosphorylation and reduced association with FYN. 2 Publications1
Mutagenesisi666K → M or R: Kinase-dead. Loss of autophosphorylation but has no effect on regulation of cell adhesion. 1 Publication1
Mutagenesisi792Y → F: Reduced phosphorylation. 1 Publication1
Mutagenesisi838Y → F: Reduced tyrosine kinase activity. 1 Publication1

Chemistry databases

GuidetoPHARMACOLOGYi1828

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000001682327 – 1004Ephrin type-A receptor 8Add BLAST978

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi339N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi406N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi431N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei615Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei838Phosphotyrosine; by autocatalysis1 Publication1

Post-translational modificationi

Phosphorylated. Phosphorylation is stimulated upon binding of its ligands including EFNA2, EFNA3 and EFNA5. Autophosphorylation on Tyr-615 is critical for association with FYN. Autophosphorylation on Tyr-838 modulates tyrosine kinase activity.2 Publications
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. ANKS1A prevents ubiquitination and degradation.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO09127
PaxDbiO09127
PeptideAtlasiO09127
PRIDEiO09127

PTM databases

iPTMnetiO09127
PhosphoSitePlusiO09127

Expressioni

Tissue specificityi

Specifically expressed in the central nervous system.

Developmental stagei

First detected at E10.5 with high levels near the midline region of the tectum and to a lower extent in discrete regions of hindbrain, the dorsal horn, of the spinal cord and in the naso-lacrimal groove. The expression decreases at E12.5 and is barely detectable at E17.5. Not detected at postnatal stages.1 Publication

Gene expression databases

BgeeiENSMUSG00000028661 Expressed in 89 organ(s), highest expression level in central nervous system
CleanExiMM_EPHA8
GenevisibleiO09127 MM

Interactioni

Subunit structurei

Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). May also form heterodimers with other ephrin receptors. Interacts with FYN; possible downstream effector of EPHA8 in regulation of cell adhesion. Interacts with PIK3CG; regulates integrin-mediated cell adhesion to substrate. Interacts with TIAM1; regulates clathrin-mediated endocytosis of EPHA8. Interacts with ANKS1A and ANKS1B; EPHA8 kinase activity-independent but stimulated by EPHA8 ubiquitination.By similarity6 Publications

Protein-protein interaction databases

IntActiO09127, 1 interactor
MINTiO09127
STRINGi10090.ENSMUSP00000030420

Structurei

3D structure databases

ProteinModelPortaliO09127
SMRiO09127
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 208Eph LBDPROSITE-ProRule annotationAdd BLAST179
Domaini327 – 437Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST111
Domaini438 – 533Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST96
Domaini634 – 895Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini929 – 993SAMPROSITE-ProRule annotationAdd BLAST65

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni563 – 569Mediates interaction with ANKS1A and ANKS1B1 Publication7
Regioni588 – 643Mediates interaction with PIK3CG and required for endocytosis1 PublicationAdd BLAST56

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1002 – 1004PDZ-bindingSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi190 – 324Cys-richAdd BLAST135

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

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118975
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiO09127
KOiK05109
OMAiWLTYPSH
OrthoDBiEOG091G00W0
TreeFamiTF315608

Family and domain databases

CDDicd10486 EphR_LBD_A8, 1 hit
cd00063 FN3, 1 hit
Gene3Di2.60.120.260, 1 hit
2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR027936 Eph_TM
IPR034287 EphA8_rcpt_lig-bd
IPR001090 Ephrin_rcpt_lig-bd_dom
IPR020691 EphrinA_rcpt8
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR008979 Galactose-bd-like_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
PANTHERiPTHR24416:SF339 PTHR24416:SF339, 1 hit
PfamiView protein in Pfam
PF14575 EphA2_TM, 1 hit
PF01404 Ephrin_lbd, 1 hit
PF00041 fn3, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PF00536 SAM_1, 1 hit
PIRSFiPIRSF000666 TyrPK_ephrin_receptor, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00615 EPH_lbd, 1 hit
SM01411 Ephrin_rec_like, 1 hit
SM00060 FN3, 2 hits
SM00454 SAM, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF49265 SSF49265, 1 hit
SSF49785 SSF49785, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView 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

Sequencei

Sequence statusi: Complete.

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

O09127-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAPARARLSP ALWVVTAAAA ATCVSAGRGE VNLLDTSTIH GDWGWLTYPA
60 70 80 90 100
HGWDSINEVD ESFRPIHTYQ VCNVMSPNQN NWLRTNWVPR DGARRVYAEI
110 120 130 140 150
KFTLRDCNSI PGVLGTCKET FNLHYLESDR DLGASTQESQ FLKIDTIAAD
160 170 180 190 200
ESFTGADLGV RRLKLNTEVR GVGPLSKRGF YLAFQDIGAC LAILSLRIYY
210 220 230 240 250
KKCPAMVRNL AAFSEAVTGA DSSSLVEVRG QCVRHSEERD TPKMYCSAEG
260 270 280 290 300
EWLVPIGKCV CSAGYEERRD ACMACELGFY KSAPGDQLCA RCPPHSHSAT
310 320 330 340 350
PAAQTCRCDL SYYRAALDPP SAACTRPPSA PVNLISSVNG TSVTLEWAPP
360 370 380 390 400
LDPGGRSDIT YNAVCRRCPW ALSHCEACGS GTRFVPQQTS LAQASLLVAN
410 420 430 440 450
LLAHMNYSFW IEAVNGVSNL SPEPRSAAVV NITTNQAAPS QVVVIRQERA
460 470 480 490 500
GQTSVSLLWQ EPEQPNGIIL EYEIKYYEKD KEMQSYSTLK AVTTRATVSG
510 520 530 540 550
LKPGTRYVFQ VRARTSAGCG RFSQAMEVET GKPRPRYDTR TIVWICLTLI
560 570 580 590 600
TGLVVLLLLL ICKKRHCGYS KAFQDSDEEK MHYQNGQAPP PVFLPLNHPP
610 620 630 640 650
GKFPETQFSA EPHTYEEPGR AGRSFTREIE ASRIHIEKII GSGESGEVCY
660 670 680 690 700
GRLQVPGQRD VPVAIKALKA GYTERQRQDF LSEAAIMGQF DHPNIIRLEG
710 720 730 740 750
VVTRGRLAMI VTEYMENGSL DAFLRTHDGQ FTIVQLVGML RGVGAGMRYL
760 770 780 790 800
SDLGYIHRDL AARNVLVDGR LVCKVSDFGL SRALEDDPEA AYTTAGGKIP
810 820 830 840 850
IRWTAPEAIA FRTFSSASDV WSFGVVMWEV LAYGERPYWN MTNQDVISSV
860 870 880 890 900
EEGYRLPAPM GCPRALHQLM LDCWHKDRAQ RPRFAHVVSV LDALVHSPES
910 920 930 940 950
LRATATVSRC PPPAFARSCF DLRAGGSGNG DLTVGDWLDS IRMGRYRDHF
960 970 980 990 1000
AAGGYSSLGM VLRMNAQDVR ALGITLMGHQ KKILGSIQTM RAQLSSTQGP

RRHL
Length:1,004
Mass (Da):110,705
Last modified:July 27, 2011 - v2
Checksum:i8530E8002A6FE502
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1000P → R in AAB39218 (PubMed:9053851).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U72207 mRNA Translation: AAB39218.1
AL627214 Genomic DNA No translation available.
CCDSiCCDS18813.1
RefSeqiNP_031965.2, NM_007939.2
UniGeneiMm.1390

Genome annotation databases

EnsembliENSMUST00000030420; ENSMUSP00000030420; ENSMUSG00000028661
GeneIDi13842
KEGGimmu:13842
UCSCiuc008vis.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U72207 mRNA Translation: AAB39218.1
AL627214 Genomic DNA No translation available.
CCDSiCCDS18813.1
RefSeqiNP_031965.2, NM_007939.2
UniGeneiMm.1390

3D structure databases

ProteinModelPortaliO09127
SMRiO09127
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO09127, 1 interactor
MINTiO09127
STRINGi10090.ENSMUSP00000030420

Chemistry databases

GuidetoPHARMACOLOGYi1828

PTM databases

iPTMnetiO09127
PhosphoSitePlusiO09127

Proteomic databases

MaxQBiO09127
PaxDbiO09127
PeptideAtlasiO09127
PRIDEiO09127

Protocols and materials databases

DNASUi13842
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030420; ENSMUSP00000030420; ENSMUSG00000028661
GeneIDi13842
KEGGimmu:13842
UCSCiuc008vis.1 mouse

Organism-specific databases

CTDi2046
MGIiMGI:109378 Epha8

Phylogenomic databases

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118975
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiO09127
KOiK05109
OMAiWLTYPSH
OrthoDBiEOG091G00W0
TreeFamiTF315608

Enzyme and pathway databases

BRENDAi2.7.10.1 3474
ReactomeiR-MMU-2682334 EPH-Ephrin signaling
R-MMU-3928663 EPHA-mediated growth cone collapse
R-MMU-3928665 EPH-ephrin mediated repulsion of cells

Miscellaneous databases

ChiTaRSiEpha8 mouse
PROiPR:O09127
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028661 Expressed in 89 organ(s), highest expression level in central nervous system
CleanExiMM_EPHA8
GenevisibleiO09127 MM

Family and domain databases

CDDicd10486 EphR_LBD_A8, 1 hit
cd00063 FN3, 1 hit
Gene3Di2.60.120.260, 1 hit
2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR027936 Eph_TM
IPR034287 EphA8_rcpt_lig-bd
IPR001090 Ephrin_rcpt_lig-bd_dom
IPR020691 EphrinA_rcpt8
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR008979 Galactose-bd-like_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
PANTHERiPTHR24416:SF339 PTHR24416:SF339, 1 hit
PfamiView protein in Pfam
PF14575 EphA2_TM, 1 hit
PF01404 Ephrin_lbd, 1 hit
PF00041 fn3, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PF00536 SAM_1, 1 hit
PIRSFiPIRSF000666 TyrPK_ephrin_receptor, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00615 EPH_lbd, 1 hit
SM01411 Ephrin_rec_like, 1 hit
SM00060 FN3, 2 hits
SM00454 SAM, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF49265 SSF49265, 1 hit
SSF49785 SSF49785, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView 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
ProtoNetiSearch...

Entry informationi

Entry nameiEPHA8_MOUSE
AccessioniPrimary (citable) accession number: O09127
Secondary accession number(s): A3KG07
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 173 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again