EPHA2_HUMAN » Ephrin type-A receptor 2

EPHA2_HUMAN » Ephrin type-A receptor 2
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
EPHA2_HUMAN » Ephrin type-A receptor 2 » Epithelial cell kinase;Tyrosine-protein kinase receptor ECK;
Hydrophobic Thickness 35.6 ± 3.0 Å
Tilt Angle 0 ± 1°
ΔGtransfer -47.5 kcal/mol
ΔGfold -20.1 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 534-558 (529-563)
Pathways

Axon guidance (KEGG)

PI3K-Akt signaling pathway (KEGG)

PDB 2x10 (27-534), 4trl (590-876), 4p2k (590-876), 1mqb (596-900), 2e8n (902-976), 3kka (903-971), 3hpn (A/B...=28-201), 2k9y (A/B=523-563), 4pdo (A/B=590-876), 3hei (A/C...=28-201), 3mx0 (A/C=27-435), 3czu (A=23-202), 3c8x (A=23-202), 3mbw (A=23-326), 3fl7 (A=23-531), 2x11 (A=27-534), 2kso (A=908-972), 3skj (E/F=23-202)
OPM 2k9y
Complexes

EPHA2:EPHA2_HUMAN

Interactions

A4, Complex: A4:EPHA2, PubMed

CADH5, Complex: EPHA2:CADH5, PubMed

EFNB1, Complex: EFNB1:EPHA2:TIAM1, PubMed

EGFR, Complex: EPHA2:EGFR, PubMed

EPHA2, Complex: Transmembrane homodimer of receptor tyrosine kinase EphA2, PDBID: 2K9Y

EPHA7, Complex: EPHA2:EPHA7, PubMed

ITA3, Complex: EPHA2:ITA3

ITAV, Complex: EPHA2:ITAV

ITB1, Complex: EPHA2:ITB1

ITB3, Complex: EPHA2:ITB3

ITB5, Complex: EPHA2:ITB5

Domains

AA: 29-201, PDBID: 2X10, Subunit A, Seq Identity:100%, Ephrin receptor ligand binding domain

AA: 330-424, PDBID: 2X10, Subunit A, Seq Identity:100%, Fibronectin type III domain

AA: 437-519, PDBID: 2X10, Subunit A, Seq Identity:100%, Fibronectin type III domain

AA: 537-610, PDBID: 1MQB, Subunit A, Seq Identity:100%, Ephrin type-A receptor 2 transmembrane domain

AA: 613-871, PDBID: 1MQB, Subunit B, Seq Identity:100%, Protein tyrosine kinase

AA: 902-966, PDBID: 2E8N, Subunit A, Seq Identity:100%, SAM domain (Sterile alpha motif)

UniProt annotation for EPHA2_HUMAN » Ephrin type-A receptor 2
FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane-bound 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. Activated by the ligand ephrin-A1/EFNA1 regulates migration, integrin-mediated adhesion, proliferation and differentiation of cells. Regulates cell adhesion and differentiation through DSG1/desmoglein-1 and inhibition of the ERK1/ERK2 (MAPK3/MAPK1, respectively) signaling pathway. May also participate in UV radiation-induced apoptosis and have a ligand- independent stimulatory effect on chemotactic cell migration. During development, may function in distinctive aspects of pattern formation and subsequently in development of several fetal tissues. Involved for instance in angiogenesis, in early hindbrain development and epithelial proliferation and branching morphogenesis during mammary gland development. Engaged by the ligand ephrin-A5/EFNA5 may regulate lens fiber cells shape and interactions and be important for lens transparency development and maintenance. With ephrin-A2/EFNA2 may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis.

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

SUBUNIT: Homodimer. Interacts with SLA. Interacts (phosphorylated form) with VAV2, VAV3 and PI3-kinase p85 subunit (PIK3R1, PIK3R2 or PIK3R3); critical for the EFNA1-induced activation of RAC1 which stimulates cell migration (By similarity). Interacts with INPPL1; regulates activated EPHA2 endocytosis and degradation. Interacts (inactivated form) with PTK2/FAK1 and interacts (EFNA1 ligand-activated form) with PTPN11; regulates integrin-mediated adhesion. Interacts with ARHGEF16, DOCK4 and ELMO2; mediates ligand-independent activation of RAC1 which stimulates cell migration. Interacts with CLDN4; phosphorylates CLDN4 and may regulate tight junctions. Interacts with ACP1. Interacts (via SAM domain) with ANKS1A (via SAM domain). Interacts with human herpes virus 8/HHV-8 glycoprotein L/gL and glycoprotein H/gH heterodimer; this interaction triggers EPHA2 phosphorylation and endocytosis, allowing virus entry. Interacts with CEMIP. Interacts with NCK1; may regulate EPHA2 activity in cell migration and adhesion.

TISSUE SPECIFICITY: Expressed in brain and glioma tissue and glioma cell lines (at protein level). Expressed most highly in tissues that contain a high proportion of epithelial cells, e.g. skin, intestine, lung, and ovary.

INDUCTION: Up-regulated by UV irradiation via a TP53-independent, MAPK-dependent mechanism.

DISEASE: Cataract 6, multiple types (CTRCT6) OMIM: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT6 includes posterior polar and age- related cortical cataracts, among others. Posterior polar cataract is a subcapsular opacity, usually disk-shaped, located at the back of the lens. Age-related cortical cataract is a developmental punctate opacity restricted to the cortex. The cataract is white or cerulean, increases in number with age, but rarely affects vision. mutations affecting the gene represented in this entry.

DISEASE: Note=Overexpressed in several cancer types and promotes malignancy.

UniProt features for EPHA2_HUMAN » Ephrin type-A receptor 2
SIGNAL 1 23 Potential.
CHAIN 24 976 Ephrin type-A receptor 2.
DOMAIN 28 206 Eph LBD.
DOMAIN 328 429 Fibronectin type-III 1.
DOMAIN 435 526 Fibronectin type-III 2.
DOMAIN 613 875 Protein kinase.
DOMAIN 904 968 SAM.
REGION 1 206 Mediates interaction with CLDN4.
REGION 606 906 Mediates interaction with ARHGEF16 and ELMO2.
REGION 886 976 Negatively regulates interaction with ARHGEF16.
MOTIF 974 976 PDZ-binding (Potential).
ACT_SITE 739 739 Proton acceptor (By similarity).
DISULFID 70 188
DISULFID 105 115
Amino Acid Sequence for EPHA2_HUMAN » Ephrin type-A receptor 2
MELQAARACF ALLWGCALAA AAAAQGKEVV LLDFAAAGGE LGWLTHPYGK GWDLMQNIMN DMPIYMYSVC NVMSGDQDNW LRTNWVYRGE AERIFIELKF TVRDCNSFPG GASSCKETFN LYYAESDLDY GTNFQKRLFT KIDTIAPDEI TVSSDFEARH VKLNVEERSV GPLTRKGFYL AFQDIGACVA LLSVRVYYKK CPELLQGLAH FPETIAGSDA PSLATVAGTC VDHAVVPPGG EEPRMHCAVD GEWLVPIGQC LCQAGYEKVE DACQACSPGF FKFEASESPC LECPEHTLPS PEGATSCECE EGFFRAPQDP ASMPCTRPPS APHYLTAVGM GAKVELRWTP PQDSGGREDI VYSVTCEQCW PESGECGPCE ASVRYSEPPH GLTRTSVTVS DLEPHMNYTF TVEARNGVSG LVTSRSFRTA SVSINQTEPP KVRLEGRSTT SLSVSWSIPP PQQSRVWKYE VTYRKKGDSN SYNVRRTEGF SVTLDDLAPD TTYLVQVQAL TQEGQGAGSK VHEFQTLSPE GSGNLAVIGG VAVGVVLLLV LAGVGFFIHR RRKNQRARQS PEDVYFSKSE QLKPLKTYVD PHTYEDPNQA VLKFTTEIHP SCVTRQKVIG AGEFGEVYKG MLKTSSGKKE VPVAIKTLKA GYTEKQRVDF LGEAGIMGQF SHHNIIRLEG VISKYKPMMI ITEYMENGAL DKFLREKDGE FSVLQLVGML RGIAAGMKYL ANMNYVHRDL AARNILVNSN LVCKVSDFGL SRVLEDDPEA TYTTSGGKIP IRWTAPEAIS YRKFTSASDV WSFGIVMWEV MTYGERPYWE LSNHEVMKAI NDGFRLPTPM DCPSAIYQLM MQCWQQERAR RPKFADIVSI LDKLIRAPDS LKTLADFDPR VSIRLPSTSG SEGVPFRTVS EWLESIKMQQ YTEHFMAAGY TAIEKVVQMT NDDIKRIGVR LPGHQKRIAY SLLGLKDQVN TVGIPI