GenomeNet

Database: UniProt
Entry: O09127
LinkDB: O09127
Original site: O09127 
ID   EPHA8_MOUSE             Reviewed;        1004 AA.
AC   O09127; A3KG07;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   09-JUL-2014, entry version 142.
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: Precursor;
GN   Name=Epha8; Synonyms=Eek;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH EFNA2; EFNA3 AND EFNA5,
RP   PHOSPHORYLATION, TOPOLOGY, AND SUBCELLULAR LOCATION.
RX   PubMed=9053851; DOI=10.1038/sj.onc.1200857;
RA   Park S., Sanchez M.P.;
RT   "The Eek receptor, a member of the Eph family of tyrosine protein
RT   kinases, can be activated by three different Eph family ligands.";
RL   Oncogene 14:533-542(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S.,
RA   She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
RA   Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
RA   Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
RA   Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
RA   Lindblad-Toh K., Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of
RT   the mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
RP   FUNCTION IN AXON GUIDANCE, AND DEVELOPMENTAL STAGE.
RX   PubMed=9214628; DOI=10.1093/emboj/16.11.3106;
RA   Park S., Frisen J., Barbacid M.;
RT   "Aberrant axonal projections in mice lacking EphA8 (Eek) tyrosine
RT   protein kinase receptors.";
RL   EMBO J. 16:3106-3114(1997).
RN   [4]
RP   FUNCTION IN CELL ADHESION, INTERACTION WITH FYN, PHOSPHORYLATION AT
RP   TYR-615 AND TYR-838, AND MUTAGENESIS OF TYR-615 AND TYR-838.
RX   PubMed=10498895; DOI=10.1038/sj.onc.1202917;
RA   Choi S., Park S.;
RT   "Phosphorylation at Tyr-838 in the kinase domain of EphA8 modulates
RT   Fyn binding to the Tyr-615 site by enhancing tyrosine kinase
RT   activity.";
RL   Oncogene 18:5413-5422(1999).
RN   [5]
RP   FUNCTION IN INTEGRIN-MEDIATED CELL ADHESION, MUTAGENESIS OF TYR-615;
RP   LYS-666 AND TYR-792, AND INTERACTION WITH PIK3CG.
RX   PubMed=11416136; DOI=10.1128/MCB.21.14.4579-4597.2001;
RA   Gu C., Park S.;
RT   "The EphA8 receptor regulates integrin activity through p110gamma
RT   phosphatidylinositol-3 kinase in a tyrosine kinase activity-
RT   independent manner.";
RL   Mol. Cell. Biol. 21:4579-4597(2001).
RN   [6]
RP   FUNCTION IN CELL MIGRATION.
RX   PubMed=12681484; DOI=10.1016/S0014-5793(03)00223-0;
RA   Gu C., Park S.;
RT   "The p110 gamma PI-3 kinase is required for EphA8-stimulated cell
RT   migration.";
RL   FEBS Lett. 540:65-70(2003).
RN   [7]
RP   FUNCTION IN MAP KINASE ACTIVATION AND NEURITE OUTGROWTH, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=15782114; DOI=10.1038/sj.onc.1208584;
RA   Gu C., Shim S., Shin J., Kim J., Park J., Han K., Park S.;
RT   "The EphA8 receptor induces sustained MAP kinase activation to promote
RT   neurite outgrowth in neuronal cells.";
RL   Oncogene 24:4243-4256(2005).
RN   [8]
RP   FUNCTION IN CELL MIGRATION AND NEURITE RETRACTION, INTERACTION WITH
RP   ANKS1A AND ANKS1B, AND SUBCELLULAR LOCATION.
RX   PubMed=17875921; DOI=10.1128/MCB.00794-07;
RA   Shin J., Gu C., Park E., Park S.;
RT   "Identification of phosphotyrosine binding domain-containing proteins
RT   as novel downstream targets of the EphA8 signaling function.";
RL   Mol. Cell. Biol. 27:8113-8126(2007).
RN   [9]
RP   UBIQUITINATION BY CBL, AND INTERACTION WITH ANKS1A.
RX   PubMed=20100865; DOI=10.1128/MCB.01605-09;
RA   Kim J., Lee H., Kim Y., Yoo S., Park E., Park S.;
RT   "The SAM domains of Anks family proteins are critically involved in
RT   modulating the degradation of EphA receptors.";
RL   Mol. Cell. Biol. 30:1582-1592(2010).
RN   [10]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH TIAM1.
RX   PubMed=20496116; DOI=10.1007/s10059-010-0075-2;
RA   Yoo S., Shin J., Park S.;
RT   "EphA8-ephrinA5 signaling and clathrin-mediated endocytosis is
RT   regulated by Tiam-1, a Rac-specific guanine nucleotide exchange
RT   factor.";
RL   Mol. Cells 29:603-609(2010).
CC   -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously GPI-
CC       anchored ephrin-A family ligands residing on adjacent cells,
CC       leading to contact-dependent bidirectional signaling into
CC       neighboring cells. The signaling pathway downstream of the
CC       receptor is referred to as forward signaling while the signaling
CC       pathway downstream of the ephrin ligand is referred to as reverse
CC       signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are
CC       able to activate EPHA8 through phosphorylation. With EFNA5 may
CC       regulate integrin-mediated cell adhesion and migration on
CC       fibronectin substrate but also neurite outgrowth. During
CC       development of the nervous system plays also a role in axon
CC       guidance. Downstream effectors of the EPHA8 signaling pathway
CC       include FYN which promotes cell adhesion upon activation by EPHA8
CC       and the MAP kinases in the stimulation of neurite outgrowth.
CC   -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
CC       [protein]-L-tyrosine phosphate.
CC   -!- SUBUNIT: Heterotetramer upon binding of the ligand. The
CC       heterotetramer is composed of an ephrin dimer and a receptor
CC       dimer. Oligomerization is probably required to induce biological
CC       responses (By similarity). May also form heterodimers with other
CC       ephrin receptors. Interacts with FYN; possible downstream effector
CC       of EPHA8 in regulation of cell adhesion. Interacts with PIK3CG;
CC       regulates integrin-mediated cell adhesion to substrate. Interacts
CC       with TIAM1; regulates clathrin-mediated endocytosis of EPHA8.
CC       Interacts with ANKS1A and ANKS1B; EPHA8 kinase activity-
CC       independent but stimulated by EPHA8 ubiquitination.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC       protein. Cell projection. Early endosome membrane. Note=Undergoes
CC       clathrin-mediated endocytosis upon EFNA5-binding and is targeted
CC       to early endosomes.
CC   -!- TISSUE SPECIFICITY: Specifically expressed in the central nervous
CC       system.
CC   -!- DEVELOPMENTAL STAGE: First detected at E10.5 with high levels near
CC       the midline region of the tectum and to a lower extent in discrete
CC       regions of hindbrain, the dorsal horn, of the spinal cord and in
CC       the naso-lacrimal groove. The expression decreases at E12.5 and is
CC       barely detectable at E17.5. Not detected at postnatal stages.
CC   -!- PTM: Phosphorylated. Phosphorylation is stimulated upon binding of
CC       its ligands including EFNA2, EFNA3 and EFNA5. Autophosphorylation
CC       on Tyr-615 is critical for association with FYN.
CC       Autophosphorylation on Tyr-838 modulates tyrosine kinase activity.
CC   -!- PTM: Ubiquitinated. Ubiquitination by CBL regulates the receptor
CC       stability and activity through proteasomal degradation. ANKS1A
CC       prevents ubiquitination and degradation.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC       kinase family. Ephrin receptor subfamily.
CC   -!- SIMILARITY: Contains 1 Eph LBD (Eph ligand-binding) domain.
CC   -!- SIMILARITY: Contains 2 fibronectin type-III domains.
CC   -!- SIMILARITY: Contains 1 protein kinase domain.
CC   -!- SIMILARITY: Contains 1 SAM (sterile alpha motif) domain.
CC   -----------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs License
CC   -----------------------------------------------------------------------
DR   EMBL; U72207; AAB39218.1; -; mRNA.
DR   EMBL; AL627214; CAM46147.1; -; Genomic_DNA.
DR   CCDS; CCDS18813.1; -.
DR   RefSeq; NP_031965.2; NM_007939.2.
DR   UniGene; Mm.1390; -.
DR   ProteinModelPortal; O09127; -.
DR   SMR; O09127; 30-533, 595-900, 925-999.
DR   IntAct; O09127; 1.
DR   MINT; MINT-5312751; -.
DR   STRING; 10090.ENSMUSP00000030420; -.
DR   PhosphoSite; O09127; -.
DR   PRIDE; O09127; -.
DR   DNASU; 13842; -.
DR   Ensembl; ENSMUST00000030420; ENSMUSP00000030420; ENSMUSG00000028661.
DR   GeneID; 13842; -.
DR   KEGG; mmu:13842; -.
DR   UCSC; uc008vis.1; mouse.
DR   CTD; 2046; -.
DR   MGI; MGI:109378; Epha8.
DR   eggNOG; COG0515; -.
DR   GeneTree; ENSGT00750000117255; -.
DR   HOGENOM; HOG000233856; -.
DR   HOVERGEN; HBG062180; -.
DR   InParanoid; A3KG07; -.
DR   KO; K05109; -.
DR   OMA; VTTRATV; -.
DR   OrthoDB; EOG7VTDM6; -.
DR   TreeFam; TF315608; -.
DR   BRENDA; 2.7.10.1; 3474.
DR   NextBio; 284680; -.
DR   PRO; PR:O09127; -.
DR   Bgee; O09127; -.
DR   CleanEx; MM_EPHA8; -.
DR   Genevestigator; O09127; -.
DR   GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR   GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0005004; F:GPI-linked ephrin receptor activity; IDA:UniProtKB.
DR   GO; GO:0005515; F:protein binding; IPI:UniProtKB.
DR   GO; GO:0007411; P:axon guidance; IMP:UniProtKB.
DR   GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR   GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0031175; P:neuron projection development; IDA:UniProtKB.
DR   GO; GO:0016322; P:neuron remodeling; IDA:UniProtKB.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR   GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IDA:UniProtKB.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR   GO; GO:0030155; P:regulation of cell adhesion; IDA:UniProtKB.
DR   GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IDA:UniProtKB.
DR   GO; GO:0006929; P:substrate-dependent cell migration; IDA:UniProtKB.
DR   Gene3D; 1.10.150.50; -; 1.
DR   Gene3D; 2.60.120.260; -; 1.
DR   Gene3D; 2.60.40.10; -; 2.
DR   InterPro; IPR027936; Eph_TM.
DR   InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom.
DR   InterPro; IPR020691; EphrinA_rcpt8.
DR   InterPro; IPR003961; Fibronectin_type3.
DR   InterPro; IPR008979; Galactose-bd-like.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR011009; Kinase-like_dom.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR001660; SAM.
DR   InterPro; IPR013761; SAM/pointed.
DR   InterPro; IPR021129; SAM_type1.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR008266; Tyr_kinase_AS.
DR   InterPro; IPR020635; Tyr_kinase_cat_dom.
DR   InterPro; IPR016257; Tyr_kinase_ephrin_rcpt.
DR   InterPro; IPR001426; Tyr_kinase_rcpt_V_CS.
DR   PANTHER; PTHR24416:SF274; PTHR24416:SF274; 1.
DR   Pfam; PF14575; EphA2_TM; 1.
DR   Pfam; PF01404; Ephrin_lbd; 1.
DR   Pfam; PF00041; fn3; 2.
DR   Pfam; PF07714; Pkinase_Tyr; 1.
DR   Pfam; PF00536; SAM_1; 1.
DR   PIRSF; PIRSF000666; TyrPK_ephrin_receptor; 1.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00615; EPH_lbd; 1.
DR   SMART; SM00060; FN3; 2.
DR   SMART; SM00454; SAM; 1.
DR   SMART; SM00219; TyrKc; 1.
DR   SUPFAM; SSF47769; SSF47769; 1.
DR   SUPFAM; SSF49265; SSF49265; 1.
DR   SUPFAM; SSF49785; SSF49785; 1.
DR   SUPFAM; SSF56112; SSF56112; 1.
DR   PROSITE; PS01186; EGF_2; 1.
DR   PROSITE; PS51550; EPH_LBD; 1.
DR   PROSITE; PS50853; FN3; 2.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR   PROSITE; PS00790; RECEPTOR_TYR_KIN_V_1; 1.
DR   PROSITE; PS00791; RECEPTOR_TYR_KIN_V_2; 1.
DR   PROSITE; PS50105; SAM_DOMAIN; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell adhesion; Cell membrane; Cell projection;
KW   Complete proteome; Developmental protein; Endosome; Glycoprotein;
KW   Kinase; Membrane; Neurogenesis; Nucleotide-binding; Phosphoprotein;
KW   Receptor; Reference proteome; Repeat; Signal; Transferase;
KW   Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW   Ubl conjugation.
FT   SIGNAL        1     26       Potential.
FT   CHAIN        27   1004       Ephrin type-A receptor 8.
FT                                /FTId=PRO_0000016823.
FT   TOPO_DOM     27    541       Extracellular (Potential).
FT   TRANSMEM    542    562       Helical; (Potential).
FT   TOPO_DOM    563   1004       Cytoplasmic (Potential).
FT   DOMAIN       30    208       Eph LBD.
FT   DOMAIN      327    437       Fibronectin type-III 1.
FT   DOMAIN      438    533       Fibronectin type-III 2.
FT   DOMAIN      634    895       Protein kinase.
FT   DOMAIN      929    993       SAM.
FT   NP_BIND     640    648       ATP (By similarity).
FT   REGION      563    569       Mediates interaction with ANKS1A and
FT                                ANKS1B.
FT   REGION      588    643       Mediates interaction with PIK3CG and
FT                                required for endocytosis.
FT   MOTIF      1002   1004       PDZ-binding (Potential).
FT   COMPBIAS    190    324       Cys-rich.
FT   ACT_SITE    759    759       Proton acceptor (By similarity).
FT   BINDING     666    666       ATP (By similarity).
FT   MOD_RES     615    615       Phosphotyrosine; by autocatalysis.
FT   MOD_RES     838    838       Phosphotyrosine; by autocatalysis.
FT   CARBOHYD    339    339       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    406    406       N-linked (GlcNAc...) (Potential).
FT   CARBOHYD    431    431       N-linked (GlcNAc...) (Potential).
FT   MUTAGEN     615    615       Y->F: Reduced phosphorylation and reduced
FT                                association with FYN.
FT   MUTAGEN     666    666       K->M,R: Kinase-dead. Loss of
FT                                autophosphorylation but has no effect on
FT                                regulation of cell adhesion.
FT   MUTAGEN     792    792       Y->F: Reduced phosphorylation.
FT   MUTAGEN     838    838       Y->F: Reduced tyrosine kinase activity.
FT   CONFLICT   1000   1000       P -> R (in Ref. 1; AAB39218).
SQ   SEQUENCE   1004 AA;  110705 MW;  8530E8002A6FE502 CRC64;
     MAPARARLSP ALWVVTAAAA ATCVSAGRGE VNLLDTSTIH GDWGWLTYPA HGWDSINEVD
     ESFRPIHTYQ VCNVMSPNQN NWLRTNWVPR DGARRVYAEI KFTLRDCNSI PGVLGTCKET
     FNLHYLESDR DLGASTQESQ FLKIDTIAAD ESFTGADLGV RRLKLNTEVR GVGPLSKRGF
     YLAFQDIGAC LAILSLRIYY KKCPAMVRNL AAFSEAVTGA DSSSLVEVRG QCVRHSEERD
     TPKMYCSAEG EWLVPIGKCV CSAGYEERRD ACMACELGFY KSAPGDQLCA RCPPHSHSAT
     PAAQTCRCDL SYYRAALDPP SAACTRPPSA PVNLISSVNG TSVTLEWAPP LDPGGRSDIT
     YNAVCRRCPW ALSHCEACGS GTRFVPQQTS LAQASLLVAN LLAHMNYSFW IEAVNGVSNL
     SPEPRSAAVV NITTNQAAPS QVVVIRQERA GQTSVSLLWQ EPEQPNGIIL EYEIKYYEKD
     KEMQSYSTLK AVTTRATVSG LKPGTRYVFQ VRARTSAGCG RFSQAMEVET GKPRPRYDTR
     TIVWICLTLI TGLVVLLLLL ICKKRHCGYS KAFQDSDEEK MHYQNGQAPP PVFLPLNHPP
     GKFPETQFSA EPHTYEEPGR AGRSFTREIE ASRIHIEKII GSGESGEVCY GRLQVPGQRD
     VPVAIKALKA GYTERQRQDF LSEAAIMGQF DHPNIIRLEG VVTRGRLAMI VTEYMENGSL
     DAFLRTHDGQ FTIVQLVGML RGVGAGMRYL SDLGYIHRDL AARNVLVDGR LVCKVSDFGL
     SRALEDDPEA AYTTAGGKIP IRWTAPEAIA FRTFSSASDV WSFGVVMWEV LAYGERPYWN
     MTNQDVISSV EEGYRLPAPM GCPRALHQLM LDCWHKDRAQ RPRFAHVVSV LDALVHSPES
     LRATATVSRC PPPAFARSCF DLRAGGSGNG DLTVGDWLDS IRMGRYRDHF AAGGYSSLGM
     VLRMNAQDVR ALGITLMGHQ KKILGSIQTM RAQLSSTQGP RRHL
//
DBGET integrated database retrieval system