EPHA8_HUMAN » Ephrin type-A receptor 8

EPHA8_HUMAN » Ephrin type-A receptor 8
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
EPHA8_HUMAN » Ephrin type-A receptor 8 » EPH- and ELK-related kinase;EPH-like kinase 3;EK3; hEK3; Tyrosine-protein kinase receptor EEK;
Hydrophobic Thickness 35.6 ± 3.4 Å
Tilt Angle 1 ± 0°
ΔGtransfer -46.9 kcal/mol
ΔGfold -22.3 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 542-564 (538-566)
Pathways

Axon guidance (KEGG)

PDB 1x5l (437-534), 3kul (602-909), 1ucv (933-1000)
OPM none
Complexes none
Interactions none
Domains

AA: 32-204, PDBID: 4L0P, Subunit A, Seq Identity:69%, Ephrin receptor ligand binding domain

AA: 330-424, PDBID: 4BK4, Subunit A, Seq Identity:53%, Fibronectin type III domain

AA: 438-524, PDBID: 1X5L, Subunit A, Seq Identity:100%, Fibronectin type III domain

AA: 542-632, PDBID: 3KUL, Subunit A, Seq Identity:100%, Ephrin type-A receptor 2 transmembrane domain

AA: 635-892, PDBID: 3KUL, Subunit A, Seq Identity:100%, Protein tyrosine kinase

AA: 932-992, PDBID: 1UCV, Subunit A, Seq Identity:100%, SAM domain (Sterile alpha motif)

UniProt annotation for EPHA8_HUMAN » Ephrin type-A receptor 8
FUNCTION: 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).

CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

SUBUNIT: 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 (By similarity). 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.

UniProt features for EPHA8_HUMAN » Ephrin type-A receptor 8
SIGNAL 1 27 Potential.
CHAIN 28 1005 Ephrin type-A receptor 8.
DOMAIN 31 209 Eph LBD.
DOMAIN 328 430 Fibronectin type-III 1.
DOMAIN 436 531 Fibronectin type-III 2.
DOMAIN 635 896 Protein kinase.
DOMAIN 930 994 SAM.
REGION 564 570 Mediates interaction with ANKS1A and ANKS1B (By similarity).
REGION 589 644 Mediates interaction with PIK3CG and required for endocytosis (By similarity).
MOTIF 1003 1005 PDZ-binding (Potential).
ACT_SITE 760 760 Proton acceptor (By similarity).
Amino Acid Sequence for EPHA8_HUMAN » Ephrin type-A receptor 8
MAPARGRLPP ALWVVTAAAA AATCVSAARG EVNLLDTSTI HGDWGWLTYP AHGWDSINEV DESFQPIHTY QVCNVMSPNQ NNWLRTSWVP RDGARRVYAE IKFTLRDCNS MPGVLGTCKE TFNLYYLESD RDLGASTQES QFLKIDTIAA DESFTGADLG VRRLKLNTEV RSVGPLSKRG FYLAFQDIGA CLAILSLRIY YKKCPAMVRN LAAFSEAVTG ADSSSLVEVR GQCVRHSEER DTPKMYCSAE GEWLVPIGKC VCSAGYEERR DACVACELGF YKSAPGDQLC ARCPPHSHSA APAAQACHCD LSYYRAALDP PSSACTRPPS APVNLISSVN GTSVTLEWAP PLDPGGRSDI TYNAVCRRCP WALSRCEACG SGTRFVPQQT SLVQASLLVA NLLAHMNYSF WIEAVNGVSD LSPEPRRAAV VNITTNQAAP SQVVVIRQER AGQTSVSLLW QEPEQPNGII LEYEIKYYEK DKEMQSYSTL KAVTTRATVS GLKPGTRYVF QVRARTSAGC GRFSQAMEVE TGKPRPRYDT RTIVWICLTL ITGLVVLLLL LICKKRHCGY SKAFQDSDEE KMHYQNGQAP PPVFLPLHHP PGKLPEPQFY AEPHTYEEPG RAGRSFTREI EASRIHIEKI IGSGDSGEVC YGRLRVPGQR DVPVAIKALK AGYTERQRRD FLSEASIMGQ FDHPNIIRLE GVVTRGRLAM IVTEYMENGS LDTFLRTHDG QFTIMQLVGM LRGVGAGMRY LSDLGYVHRD LAARNVLVDS NLVCKVSDFG LSRVLEDDPD AAYTTTGGKI PIRWTAPEAI AFRTFSSASD VWSFGVVMWE VLAYGERPYW NMTNRDVISS VEEGYRLPAP MGCPHALHQL MLDCWHKDRA QRPRFSQIVS VLDALIRSPE SLRATATVSR CPPPAFVRSC FDLRGGSGGG GGLTVGDWLD SIRMGRYRDH FAAGGYSSLG MVLRMNAQDV RALGITLMGH QKKILGSIQT MRAQLTSTQG PRRHL