EPHA8_RAT
ID EPHA8_RAT Reviewed; 372 AA.
AC P29321;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Ephrin type-A receptor 8;
DE EC=2.7.10.1;
DE AltName: Full=EPH- and ELK-related kinase;
DE AltName: Full=Tyrosine-protein kinase receptor EEK;
DE Flags: Fragment;
GN Name=Epha8; Synonyms=Eek;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=1648701;
RA Chan J., Watt V.M.;
RT "eek and erk, new members of the eph subclass of receptor protein-tyrosine
RT kinases.";
RL Oncogene 6:1057-1061(1991).
CC -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously GPI-
CC anchored ephrin-A family ligands residing on adjacent cells, leading to
CC contact-dependent bidirectional signaling into neighboring cells. The
CC signaling pathway downstream of the receptor is referred to as forward
CC signaling while the signaling pathway downstream of the ephrin ligand
CC is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2,
CC EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation.
CC With EFNA5 may regulate integrin-mediated cell adhesion and migration
CC on fibronectin substrate but also neurite outgrowth. During development
CC of the nervous system also plays a role in axon guidance. Downstream
CC effectors of the EPHA8 signaling pathway include FYN which promotes
CC cell adhesion upon activation by EPHA8 and the MAP kinases in the
CC stimulation of neurite outgrowth (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Heterotetramer upon binding of the ligand. The heterotetramer
CC is composed of an ephrin dimer and a receptor dimer. Oligomerization is
CC probably required to induce biological responses. May also form
CC heterodimers with other ephrin receptors. Interacts with FYN; possible
CC downstream effector of EPHA8 in regulation of cell adhesion. Interacts
CC with PIK3CG; regulates integrin-mediated cell adhesion to substrate.
CC Interacts with TIAM1; regulates clathrin-mediated endocytosis of EPHA8.
CC Interacts with ANKS1A and ANKS1B; EPHA8 kinase activity-independent but
CC stimulated by EPHA8 ubiquitination (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O09127};
CC Single-pass type I membrane protein {ECO:0000255}. Cell projection
CC {ECO:0000250|UniProtKB:O09127}. Early endosome membrane
CC {ECO:0000250|UniProtKB:O09127}. Note=Undergoes clathrin-mediated
CC endocytosis upon EFNA5-binding and is targeted to early endosomes.
CC {ECO:0000250|UniProtKB:O09127}.
CC -!- TISSUE SPECIFICITY: Most abundant in brain.
CC -!- PTM: Phosphorylated. Phosphorylation is stimulated upon binding of its
CC ligands including EFNA2, EFNA3 and EFNA5. Autophosphorylation on Tyr-
CC 206 modulates tyrosine kinase activity (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Ubiquitination by CBL regulates the receptor
CC stability and activity through proteasomal degradation. ANKS1A prevents
CC ubiquitination and degradation (By similarity). {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X59290; CAA41979.1; -; mRNA.
DR PIR; S23363; S23363.
DR AlphaFoldDB; P29321; -.
DR SMR; P29321; -.
DR STRING; 10116.ENSRNOP00000017559; -.
DR PhosphoSitePlus; P29321; -.
DR PaxDb; P29321; -.
DR UCSC; RGD:708543; rat.
DR RGD; 708543; Epha8.
DR eggNOG; KOG0196; Eukaryota.
DR InParanoid; P29321; -.
DR PhylomeDB; P29321; -.
DR Reactome; R-RNO-2682334; EPH-Ephrin signaling.
DR Reactome; R-RNO-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-RNO-3928665; EPH-ephrin mediated repulsion of cells.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
DR GO; GO:0019838; F:growth factor binding; ISO:RGD.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; ISO:RGD.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0016322; P:neuron remodeling; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; ISS:UniProtKB.
DR GO; GO:0006929; P:substrate-dependent cell migration; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 1.10.150.50; -; 1.
DR InterPro; IPR020691; EphrinA_rcpt8.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR PANTHER; PTHR24416:SF339; PTHR24416:SF339; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00536; SAM_1; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell adhesion; Cell membrane; Cell projection;
KW Developmental protein; Endosome; Kinase; Membrane; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome;
KW Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN <1..372
FT /note="Ephrin type-A receptor 8"
FT /id="PRO_0000160273"
FT DOMAIN 2..263
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 297..372
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT MOTIF 370..372
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 127
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 8..16
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 206
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:O09127"
FT NON_TER 1
SQ SEQUENCE 372 AA; 41233 MW; C8FDCFB5A6904BA5 CRC64;
RIHIEKIIGS GESGEVCYGR LQVPGQRDVP VAIKALKAGY TERQRQDFLR EAAIMGQFDH
PNIIRLEGVV TRGRLAMIVT EYMENGSLDA FLRTHDGQFT ILQLVGMLKG VGAGMRYLSD
LGYIHRDLAA RNILVDGRLV CKVSDFGLSR ALEDDPEAAY TTAGGKIPIR WTAPEAIAFR
TFSSASDVWS FGVVMWEVLA YGERPYWNMT NQDVISSVEE GYRLPAPMGC PRALHQLMLD
CWHKDRAQRP RFSHVVSVLE ALVHSPESLR ATATVSRCPA PAFARSCFDL RAGGNGNGDL
TVGDWLDSIR MGRYRDHFAA GGYSSLGMVL HMNAQDVRAL GITLMGHQKK ILGSIQTMRS
QLSCTQGPRR HL
