EPHB2_CHICK
ID EPHB2_CHICK Reviewed; 1004 AA.
AC P28693;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 3.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Ephrin type-B receptor 2;
DE EC=2.7.10.1;
DE AltName: Full=EPH-like kinase 5;
DE Short=EK5;
DE Short=cEK5;
DE Contains:
DE RecName: Full=EphB2/CTF1 {ECO:0000250|UniProtKB:P54763};
DE Contains:
DE RecName: Full=EphB2/CTF2 {ECO:0000250|UniProtKB:P54763};
DE Flags: Precursor;
GN Name=EPHB2; Synonyms=CEK5;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC TISSUE=Embryo;
RX PubMed=1664238; DOI=10.1091/mbc.2.7.523;
RA Pasquale E.B.;
RT "Identification of chicken embryo kinase 5, a developmentally regulated
RT receptor-type tyrosine kinase of the Eph family.";
RL Cell Regul. 2:523-534(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Brain;
RX PubMed=8510926;
RA Sajjadi F.G., Pasquale E.B.;
RT "Five novel avian Eph-related tyrosine kinases are differentially
RT expressed.";
RL Oncogene 8:1807-1813(1993).
CC -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously
CC transmembrane ephrin-B family ligands residing on adjacent cells,
CC leading to contact-dependent bidirectional signaling into neighboring
CC cells. The signaling pathway downstream of the receptor is referred to
CC as forward signaling while the signaling pathway downstream of the
CC ephrin ligand is referred to as reverse signaling. Functions in axon
CC guidance during development. In addition to axon guidance, also
CC regulates dendritic spines development and maturation and stimulates
CC the formation of excitatory synapses (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- SUBUNIT: Heterotetramer upon binding of the ligand. The heterotetramer
CC is composed of an ephrin dimer and a receptor dimer. Oligomerization is
CC probably required to induce biological responses (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC P28693; P00520: Abl1; Xeno; NbExp=5; IntAct=EBI-6725885, EBI-914519;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Cell projection, axon {ECO:0000250}.
CC Cell projection, dendrite {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long; Synonyms=CEK5+;
CC IsoId=P28693-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P28693-2; Sequence=VSP_003018;
CC -!- TISSUE SPECIFICITY: Wide tissue distribution throughout development and
CC sustained expression in adult brain. The longer form (CEK5+) is
CC specifically expressed in the central nervous system.
CC -!- PTM: Ligand binding induces cleavage by matrix metalloproteinases
CC (MMPs) such as MMP7/MMP9, producing an EphB2/N-terminal fragment (NTF)
CC and a C-terminal long fragment (EphB2-LF). EphB2-LF is further cleaved
CC by MMPs, producing EphB2/CTF1 which is further cleaved by the
CC PS1/gamma-secretase producing EphB2/CTF2.
CC {ECO:0000250|UniProtKB:P54763}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA48667.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M62325; AAA48667.1; ALT_INIT; mRNA.
DR PIR; A56599; A56599.
DR RefSeq; NP_996834.1; NM_206951.3.
DR PDB; 1SGG; NMR; -; A=924-998.
DR PDBsum; 1SGG; -.
DR AlphaFoldDB; P28693; -.
DR BMRB; P28693; -.
DR SMR; P28693; -.
DR BioGRID; 676759; 1.
DR IntAct; P28693; 3.
DR STRING; 9031.ENSGALP00000007541; -.
DR iPTMnet; P28693; -.
DR PaxDb; P28693; -.
DR GeneID; 396513; -.
DR KEGG; gga:396513; -.
DR CTD; 2048; -.
DR VEuPathDB; HostDB:geneid_396513; -.
DR eggNOG; KOG0196; Eukaryota.
DR InParanoid; P28693; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; P28693; -.
DR BRENDA; 2.7.10.1; 1306.
DR EvolutionaryTrace; P28693; -.
DR PRO; PR:P28693; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0007413; P:axonal fasciculation; ISS:UniProtKB.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; IBA:GO_Central.
DR GO; GO:0060996; P:dendritic spine development; ISS:UniProtKB.
DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0051965; P:positive regulation of synapse assembly; ISS:UniProtKB.
DR GO; GO:0021963; P:spinothalamic tract morphogenesis; IDA:CACAO.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10477; EphR_LBD_B2; 1.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034238; EphB2_rcpt_lig-bd.
DR InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR011641; Tyr-kin_ephrin_A/B_rcpt-like.
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 Pfam; PF14575; EphA2_TM; 1.
DR Pfam; PF01404; Ephrin_lbd; 1.
DR Pfam; PF07699; Ephrin_rec_like; 1.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 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 SUPFAM; SSF57184; SSF57184; 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 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Cell projection; Developmental protein; Disulfide bond; Glycoprotein;
KW Kinase; Membrane; Neurogenesis; Nucleotide-binding; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1004
FT /note="Ephrin type-B receptor 2"
FT /id="PRO_0000016829"
FT CHAIN 537..1004
FT /note="EphB2/CTF1"
FT /evidence="ECO:0000250|UniProtKB:P54763"
FT /id="PRO_0000445965"
FT CHAIN 563..1004
FT /note="EphB2/CTF2"
FT /evidence="ECO:0000250|UniProtKB:P54763"
FT /id="PRO_0000445966"
FT TOPO_DOM 20..544
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 545..565
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 566..1004
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 21..203
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 325..435
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 436..531
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 639..902
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 931..995
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT MOTIF 1002..1004
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 764
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 645..653
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 671
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 536..537
FT /note="Cleavage; by a metalloproteinase"
FT /evidence="ECO:0000250|UniProtKB:P54763"
FT SITE 562..563
FT /note="Cleavage; by gamma-secretase/PS1"
FT /evidence="ECO:0000250|UniProtKB:P54763"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 429
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 478
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 483
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 63..185
FT /evidence="ECO:0000250"
FT DISULFID 98..108
FT /evidence="ECO:0000250"
FT VAR_SEQ 591..606
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:1664238,
FT ECO:0000303|PubMed:8510926"
FT /id="VSP_003018"
FT HELIX 936..942
FT /evidence="ECO:0007829|PDB:1SGG"
FT HELIX 946..948
FT /evidence="ECO:0007829|PDB:1SGG"
FT HELIX 949..955
FT /evidence="ECO:0007829|PDB:1SGG"
FT HELIX 962..965
FT /evidence="ECO:0007829|PDB:1SGG"
FT HELIX 968..974
FT /evidence="ECO:0007829|PDB:1SGG"
FT HELIX 981..995
FT /evidence="ECO:0007829|PDB:1SGG"
SQ SEQUENCE 1004 AA; 111963 MW; 8D26213970ECC6E0 CRC64;
MGPLWFCCLP LALLPLLAAV EETLMDSTTA TAELGWMVHP PSGWEEVSGY DENMNTIRTY
QVCNVFESSQ NNWLRTKYIR RRGAHRIHVE MKFSVRDCSS IPNVPGSCKE TFNLYYYESD
FDSATKTFPN WMENPWMKVD TIAADESFSQ VDLGGRVMKI NTEVRSFGPV SKNGFYLAFQ
DYGGCMSLIA VRVFYRKCPR VIQNGAVFQE TLSGAESTSL VAARGTCISN AEEVDVPIKL
YCNGDGEWLV PIGRCMCRPG YESVENGTVC RGCPSGTFKA SQGDEGCVHC PINSRTTSEG
ATNCVCRNGY YRADADPVDM PCTTIPSAPQ AVISSVNETS LMLEWTPPRD SGGREDLVYN
IICKSCGSGR GACTRCGDNV QFAPRQLGLT EPRIYISDLL AHTQYTFEIQ AVNGVTDQSP
FSPQFASVNI TTNQAAPSAV SIMHQVSRTV DSITLSWSQP DQPNGVILDY ELQYYEKNLS
ELNSTAVKSP TNTVTVQNLK AGTIYVFQVR ARTVAGYGRY SGKMYFQTMT EAEYQTSVQE
KLPLIIGSSA AGLVFLIAVV VIIIVCNRRR GFERADSEYT DKLQHYTSGH STYRGPPPGL
GVRLFVMTPG MKIYIDPFTY EDPNEAVREF AKEIDISCVK IEQVIGAGEF GEVCSGHLKL
PGKREIFVAI KTLKSGYTEK QRRDFLSEAS IMGQFDHPNV IHLEGVVTKS SPVMIITEFM
ENGSLDSFLR QNDGQFTVIQ LVGMLRGIAA GMKYLADMNY VHRDLAARNI LVNSNLVCKV
SDFGLSRFLE DDTSDPTYTS ALGGKIPIRW TAPEAIQYRK FTSASDVWSY GIVMWEVMSY
GERPYWDMTN QDVINAIEQD YRLPPPMDCP NALHQLMLDC WQKDRNHRPK FGQIVNTLDK
MIRNPNSLKA MAPLSSGVNL PLLDRTIPDY TSFNTVDEWL DAIKMSQYKE SFASAGFTTF
DIVSQMTVED ILRVGVTLAG HQKKILNSIQ VMRAQMNQIQ SVEV
