EPHB2_HUMAN » Ephrin type-B receptor 2

EPHB2_HUMAN » Ephrin type-B receptor 2
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Topology in Plasma membrane
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EPHB2_HUMAN » Ephrin type-B receptor 2 » Developmentally-regulated Eph-related tyrosine kinase;ELK-related tyrosine kinase;EPH tyrosine kinase 3;EPH-like kinase 5;EK5; hEK5; Renal carcinoma antigen NY-REN-47;Tyrosine-protein kinase TYRO5;Tyrosine-protein kinase receptor EPH-3;
Hydrophobic Thickness 31.6 ± 2.2 Å
Tilt Angle 8 ± 6°
ΔGtransfer -42.1 kcal/mol
ΔGfold -16.9 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 543-565 (543-568)
Pathways

Axon guidance (KEGG)

Developmental Biology (Reactome)

PDB 3zfm (604-898), 1f0m (908-985), 1b4f (A/B...=908-985), 2qbx (A/B=20-196)
OPM none
Complexes

EFNB2:EPHB2_MOUSE

EPHB2:EPHB2_HUMAN

Interactions

ADA17, Complex: ADA17:EPHB2, PubMed

ALK, Complex: EPHB2:ALK, PubMed

BCL2, Complex: BCL2:EPHB2, PubMed

EFNB1, Complex: EFNB1:EPHB2, PubMed

EFNB2, Complex: EFNB2:EPHB2, PDBID: 1kgy

EPHB2, Complex: Homodimer of ephrin type-b receptor 2, PDBID: 2QBX

RYK, Complex: EPHB2:RYK, PubMed

SDC2, Complex: SDC2:EPHB2, PubMed

Domains

AA: 21-197, PDBID: 2QBX, Subunit A, Seq Identity:100%, Ephrin receptor ligand binding domain

AA: 261-304, Putative ephrin-receptor like

AA: 326-421, PDBID: 4BK4, Subunit A, Seq Identity:51%, Fibronectin type III domain

AA: 434-520, PDBID: 2DJS, Subunit A, Seq Identity:55%, Fibronectin type III domain

AA: 544-618, PDBID: 3ZFM, Subunit A, Seq Identity:100%, Ephrin type-A receptor 2 transmembrane domain

AA: 621-880, PDBID: 1JPA, Subunit A, Seq Identity:100%, Protein tyrosine kinase

AA: 911-975, PDBID: 1B4F, Subunit H, Seq Identity:100%, SAM domain (Sterile alpha motif)

UniProt annotation for EPHB2_HUMAN » Ephrin type-B receptor 2
FUNCTION: Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor.

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 (By similarity). Interacts (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain) (By similarity). Interacts with ARHGEF15; mediates ARHGEF15 phosphorylation, ubiquitination and degradation by the proteasome. Interacts with AQP1; involved in endolymph production in the inner ear.

TISSUE SPECIFICITY: Brain, heart, lung, kidney, placenta, pancreas, liver and skeletal muscle. Preferentially expressed in fetal brain.

DISEASE: Prostate cancer (PC) OMIM: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. entry may be involved in disease pathogenesis. EPHB2 mutations have been found in a prostate cancer cell line derived from a brain metastasis.

UniProt features for EPHB2_HUMAN » Ephrin type-B receptor 2
SIGNAL 1 18 Potential.
CHAIN 19 1055 Ephrin type-B receptor 2.
DOMAIN 20 202 Eph LBD.
DOMAIN 325 426 Fibronectin type-III 1.
DOMAIN 432 527 Fibronectin type-III 2.
DOMAIN 621 884 Protein kinase.
DOMAIN 913 977 SAM.
MOTIF 984 986 PDZ-binding (in isoform 2) (Potential).
ACT_SITE 746 746 Proton acceptor (By similarity).
DISULFID 62 184
DISULFID 97 107
Amino Acid Sequence for EPHB2_HUMAN » Ephrin type-B receptor 2
MALRRLGAAL LLLPLLAAVE ETLMDSTTAT AELGWMVHPP SGWEEVSGYD ENMNTIRTYQ VCNVFESSQN NWLRTKFIRR RGAHRIHVEM KFSVRDCSSI PSVPGSCKET FNLYYYEADF DSATKTFPNW MENPWVKVDT IAADESFSQV DLGGRVMKIN TEVRSFGPVS RSGFYLAFQD YGGCMSLIAV RVFYRKCPRI IQNGAIFQET LSGAESTSLV AARGSCIANA EEVDVPIKLY CNGDGEWLVP IGRCMCKAGF EAVENGTVCR GCPSGTFKAN QGDEACTHCP INSRTTSEGA TNCVCRNGYY RADLDPLDMP CTTIPSAPQA VISSVNETSL MLEWTPPRDS GGREDLVYNI ICKSCGSGRG ACTRCGDNVQ YAPRQLGLTE PRIYISDLLA HTQYTFEIQA VNGVTDQSPF SPQFASVNIT TNQAAPSAVS IMHQVSRTVD SITLSWSQPD QPNGVILDYE LQYYEKELSE YNATAIKSPT NTVTVQGLKA GAIYVFQVRA RTVAGYGRYS GKMYFQTMTE AEYQTSIQEK LPLIIGSSAA GLVFLIAVVV IAIVCNRRGF ERADSEYTDK LQHYTSGHMT PGMKIYIDPF TYEDPNEAVR EFAKEIDISC VKIEQVIGAG EFGEVCSGHL KLPGKREIFV AIKTLKSGYT EKQRRDFLSE ASIMGQFDHP NVIHLEGVVT KSTPVMIITE FMENGSLDSF LRQNDGQFTV IQLVGMLRGI AAGMKYLADM NYVHRDLAAR NILVNSNLVC KVSDFGLSRF LEDDTSDPTY TSALGGKIPI RWTAPEAIQY RKFTSASDVW SYGIVMWEVM SYGERPYWDM TNQDVINAIE QDYRLPPPMD CPSALHQLML DCWQKDRNHR PKFGQIVNTL DKMIRNPNSL KAMAPLSSGI NLPLLDRTIP DYTSFNTVDE WLEAIKMGQY KESFANAGFT SFDVVSQMMM EDILRVGVTL AGHQKKILNS IQVMRAQMNQ IQSVEGQPLA RRPRATGRTK RCQPRDVTKK TCNSNDGKKK GMGKKKTDPG RGREIQGIFF KEDSHKESND CSCGG