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Protein

Ephrin type-A receptor 8

Gene

Epha8

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei34 – 341ATPPROSITE-ProRule annotation
Active sitei127 – 1271Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi8 – 169ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Cell adhesion, Neurogenesis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi708543. Epha8.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein Sequence analysis
  • Cell projection By similarity
  • Early endosome membrane By similarity

  • Note: Undergoes clathrin-mediated endocytosis upon EFNA5-binding and is targeted to early endosomes.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – 372›372Ephrin type-A receptor 8PRO_0000160273Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei206 – 2061Phosphotyrosine; by autocatalysisBy similarity

Post-translational modificationi

Phosphorylated. Phosphorylation is stimulated upon binding of its ligands including EFNA2, EFNA3 and EFNA5. Autophosphorylation on Tyr-206 modulates tyrosine kinase activity (By similarity).By similarity
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. ANKS1A prevents ubiquitination and degradation (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP29321.
PRIDEiP29321.

PTM databases

PhosphoSiteiP29321.

Expressioni

Tissue specificityi

Most abundant in brain.

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. 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 similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000017559.

Structurei

3D structure databases

ProteinModelPortaliP29321.
SMRiP29321. Positions 2-266, 293-367.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 263262Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini297 – 37276SAMPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi370 – 3723PDZ-bindingSequence analysis

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiP29321.
PhylomeDBiP29321.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
InterProiIPR020691. EphrinA_rcpt8.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PANTHERiPTHR24416:SF339. PTHR24416:SF339. 1 hit.
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Fragment.

P29321-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
RIHIEKIIGS GESGEVCYGR LQVPGQRDVP VAIKALKAGY TERQRQDFLR
60 70 80 90 100
EAAIMGQFDH PNIIRLEGVV TRGRLAMIVT EYMENGSLDA FLRTHDGQFT
110 120 130 140 150
ILQLVGMLKG VGAGMRYLSD LGYIHRDLAA RNILVDGRLV CKVSDFGLSR
160 170 180 190 200
ALEDDPEAAY TTAGGKIPIR WTAPEAIAFR TFSSASDVWS FGVVMWEVLA
210 220 230 240 250
YGERPYWNMT NQDVISSVEE GYRLPAPMGC PRALHQLMLD CWHKDRAQRP
260 270 280 290 300
RFSHVVSVLE ALVHSPESLR ATATVSRCPA PAFARSCFDL RAGGNGNGDL
310 320 330 340 350
TVGDWLDSIR MGRYRDHFAA GGYSSLGMVL HMNAQDVRAL GITLMGHQKK
360 370
ILGSIQTMRS QLSCTQGPRR HL
Length:372
Mass (Da):41,233
Last modified:December 1, 1992 - v1
Checksum:iC8FDCFB5A6904BA5
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59290 mRNA. Translation: CAA41979.1.
PIRiS23363.
UniGeneiRn.62934.

Genome annotation databases

UCSCiRGD:708543. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X59290 mRNA. Translation: CAA41979.1.
PIRiS23363.
UniGeneiRn.62934.

3D structure databases

ProteinModelPortaliP29321.
SMRiP29321. Positions 2-266, 293-367.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000017559.

PTM databases

PhosphoSiteiP29321.

Proteomic databases

PaxDbiP29321.
PRIDEiP29321.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:708543. rat.

Organism-specific databases

RGDi708543. Epha8.

Phylogenomic databases

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiP29321.
PhylomeDBiP29321.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
InterProiIPR020691. EphrinA_rcpt8.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PANTHERiPTHR24416:SF339. PTHR24416:SF339. 1 hit.
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "eek and erk, new members of the eph subclass of receptor protein-tyrosine kinases."
    Chan J., Watt V.M.
    Oncogene 6:1057-1061(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Wistar.
    Tissue: Brain.

Entry informationi

Entry nameiEPHA8_RAT
AccessioniPrimary (citable) accession number: P29321
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: December 1, 1992
Last modified: January 20, 2016
This is version 139 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.