EPHA3_HUMAN » Ephrin type-A receptor 3

EPHA3_HUMAN » Ephrin type-A receptor 3
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
EPHA3_HUMAN » Ephrin type-A receptor 3 » EPH-like kinase 4;EK4; hEK4; HEK;Human embryo kinase; Tyrosine-protein kinase TYRO4;Tyrosine-protein kinase receptor ETK1;Eph-like tyrosine kinase 1;
Hydrophobic Thickness 32.0 ± 3.0 Å
Tilt Angle 1 ± 2°
ΔGtransfer -45.7 kcal/mol
ΔGfold -24.3 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 539-567 (538-574)
Pathways

Axon guidance (KEGG)

PDB 2qo2 (577-947), 2qoq (577-947), 2qoo (577-947), 2qon (577-947), 2qol (577-947), 2qok (577-947), 2qoi (577-947), 2qod (577-947), 2qof (577-947), 2qo9 (577-947), 2qo7 (577-947), 2gsf (577-947), 4p5z (606-947), 4p5q (606-947), 3dzq (609-947), 4g2f (609-947), 4gk2 (609-947), 4gk3 (609-947), 4gk4 (609-947), 4p4c (609-947), 2qob (609-947), 2qoc (609-947), 4l0p (A=29-201), 3fxx (A=577-947), 3fy2 (A=577-947)
OPM none
Complexes none
Interactions

ADA10, Complex: ADA10:EPHA3, PubMed

EFNB1, Complex: EFNB1:EPHA3, PubMed

EFNB2, Complex: EFNB2:EPHA3, PubMed

EPHA7, Complex: EPHA3:EPHA7, PubMed

Domains

AA: 30-202, PDBID: 4L0P, Subunit A, Seq Identity:100%, Ephrin receptor ligand binding domain

AA: 263-306, Putative ephrin-receptor like

AA: 327-422, PDBID: 4BK4, Subunit A, Seq Identity:50%, Fibronectin type III domain

AA: 437-521, PDBID: 2DJS, Subunit A, Seq Identity:51%, Fibronectin type III domain

AA: 542-618, PDBID: 2GSF, Subunit A, Seq Identity:100%, Ephrin type-A receptor 2 transmembrane domain

AA: 621-878, PDBID: 2GSF, Subunit A, Seq Identity:100%, Protein tyrosine kinase

AA: 908-973, PDBID: 3H8M, Subunit A, Seq Identity:38%, SAM domain (Sterile alpha motif)

UniProt annotation for EPHA3_HUMAN » Ephrin type-A receptor 3
FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin 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. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development.

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. Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function. Interacts with NCK1 (via SH2 domain); mediates EFNA5-EPHA3 signaling (By similarity). Interacts (phosphorylated) with PTPN1; dephosphorylates EPHA3 and may regulate its trafficking and function. Interacts (phosphorylated) with CRK; mediates EFNA5- EPHA3 signaling through RHOA GTPase activation.

TISSUE SPECIFICITY: Widely expressed. Highest level in placenta.

DISEASE: Colorectal cancer (CRC) OMIM: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. Note=The gene represented in this entry may be involved in disease pathogenesis.

UniProt features for EPHA3_HUMAN » Ephrin type-A receptor 3
SIGNAL 1 20
CHAIN 21 983 Ephrin type-A receptor 3.
DOMAIN 29 207 Eph LBD.
DOMAIN 325 429 Fibronectin type-III 1.
DOMAIN 437 528 Fibronectin type-III 2.
DOMAIN 621 882 Protein kinase.
DOMAIN 911 975 SAM.
MOTIF 981 983 PDZ-binding (Potential).
ACT_SITE 746 746 Proton acceptor (By similarity).
Amino Acid Sequence for EPHA3_HUMAN » Ephrin type-A receptor 3
MDCQLSILLL LSCSVLDSFG ELIPQPSNEV NLLDSKTIQG ELGWISYPSH GWEEISGVDE HYTPIRTYQV CNVMDHSQNN WLRTNWVPRN SAQKIYVELK FTLRDCNSIP LVLGTCKETF NLYYMESDDD HGVKFREHQF TKIDTIAADE SFTQMDLGDR ILKLNTEIRE VGPVNKKGFY LAFQDVGACV ALVSVRVYFK KCPFTVKNLA MFPDTVPMDS QSLVEVRGSC VNNSKEEDPP RMYCSTEGEW LVPIGKCSCN AGYEERGFMC QACRPGFYKA LDGNMKCAKC PPHSSTQEDG SMNCRCENNY FRADKDPPSM ACTRPPSSPR NVISNINETS VILDWSWPLD TGGRKDVTFN IICKKCGWNI KQCEPCSPNV RFLPRQFGLT NTTVTVTDLL AHTNYTFEID AVNGVSELSS PPRQFAAVSI TTNQAAPSPV LTIKKDRTSR NSISLSWQEP EHPNGIILDY EVKYYEKQEQ ETSYTILRAR GTNVTISSLK PDTIYVFQIR ARTAAGYGTN SRKFEFETSP DSFSISGESS QVVMIAISAA VAIILLTVVI YVLIGRFCGY KSKHGADEKR LHFGNGHLKL PGLRTYVDPH TYEDPTQAVH EFAKELDATN ISIDKVVGAG EFGEVCSGRL KLPSKKEISV AIKTLKVGYT EKQRRDFLGE ASIMGQFDHP NIIRLEGVVT KSKPVMIVTE YMENGSLDSF LRKHDAQFTV IQLVGMLRGI ASGMKYLSDM GYVHRDLAAR NILINSNLVC KVSDFGLSRV LEDDPEAAYT TRGGKIPIRW TSPEAIAYRK FTSASDVWSY GIVLWEVMSY GERPYWEMSN QDVIKAVDEG YRLPPPMDCP AALYQLMLDC WQKDRNNRPK FEQIVSILDK LIRNPGSLKI ITSAAARPSN LLLDQSNVDI TTFRTTGDWL NGVWTAHCKE IFTGVEYSSC DTIAKISTDD MKKVGVTVVG PQKKIISSIK ALETQSKNGP VPV