ID EPB4B_DANRE Reviewed; 976 AA.
AC O73878; B3DIW7; F1QR66;
DT 05-JUN-2019, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 2.
DT 27-MAR-2024, entry version 173.
DE RecName: Full=Ephrin type-B receptor 4b {ECO:0000250|UniProtKB:P54760};
DE EC=2.7.10.1 {ECO:0000255|PROSITE-ProRule:PRU00159};
DE AltName: Full=Eph receptor B4b {ECO:0000312|ZFIN:ZDB-GENE-990415-65};
DE AltName: Full=Eph-like receptor tyrosine kinase rtk8 {ECO:0000312|EMBL:CAA06302.1};
DE Flags: Precursor;
GN Name=ephb4b {ECO:0000312|ZFIN:ZDB-GENE-990415-65};
GN Synonyms=rtk8 {ECO:0000303|PubMed:27747378};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=27747378; DOI=10.1007/s004270050082;
RA Cooke J.E., Xu Q., Wilson S.W., Holder N.;
RT "Characterisation of five novel zebrafish Eph-related receptor tyrosine
RT kinases suggests roles in patterning the neural plate.";
RL Dev. Genes Evol. 206:515-531(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION.
RX PubMed=9765210; DOI=10.1101/gad.12.19.3096;
RA Durbin L., Brennan C., Shiomi K., Cooke J., Barrios A., Shanmugalingam S.,
RA Guthrie B., Lindberg R., Holder N.;
RT "Eph signaling is required for segmentation and differentiation of the
RT somites.";
RL Genes Dev. 12:3096-3109(1998).
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. Together with its
CC cognate ligand/functional ligand EFNB2 is involved in the regulation of
CC cell adhesion and cell migration, and plays a central role in heart
CC morphogenesis, angiogenesis and blood vessel remodeling and
CC permeability. EPHB4-mediated forward signaling controls cellular
CC repulsion and segregation from EFNB2-expressing cells (By similarity).
CC Involved in somitogenesis (PubMed:9765210).
CC {ECO:0000250|UniProtKB:P54760, ECO:0000269|PubMed:9765210}.
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:PRU00159};
CC -!- INTERACTION:
CC O73878; O73874: efnb2a; NbExp=2; IntAct=EBI-42473330, EBI-42473274;
CC O73878; Q90Z31: efnb3; NbExp=2; IntAct=EBI-42473330, EBI-42477337;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P54760};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P54760}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; AJ005029; CAA06302.1; -; mRNA.
DR EMBL; CU694439; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FO904964; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC163275; AAI63275.1; -; mRNA.
DR RefSeq; NP_571492.1; NM_131417.1.
DR AlphaFoldDB; O73878; -.
DR SMR; O73878; -.
DR IntAct; O73878; 2.
DR STRING; 7955.ENSDARP00000088414; -.
DR PaxDb; 7955-ENSDARP00000088414; -.
DR DNASU; 30691; -.
DR GeneID; 30691; -.
DR KEGG; dre:30691; -.
DR AGR; ZFIN:ZDB-GENE-990415-65; -.
DR CTD; 30691; -.
DR ZFIN; ZDB-GENE-990415-65; ephb4b.
DR eggNOG; KOG0196; Eukaryota.
DR InParanoid; O73878; -.
DR OMA; YCYRRRV; -.
DR OrthoDB; 1614410at2759; -.
DR PhylomeDB; O73878; -.
DR TreeFam; TF315608; -.
DR Reactome; R-DRE-2682334; EPH-Ephrin signaling.
DR Reactome; R-DRE-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-DRE-3928665; EPH-ephrin mediated repulsion of cells.
DR PRO; PR:O73878; -.
DR Proteomes; UP000000437; Chromosome 23.
DR Bgee; ENSDARG00000027112; Expressed in anterior neural keel and 49 other cell types or tissues.
DR ExpressionAtlas; O73878; baseline and differential.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005003; F:ephrin receptor activity; IEA:InterPro.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0070121; P:Kupffer's vesicle development; IMP:ZFIN.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0001756; P:somitogenesis; IMP:UniProtKB.
DR CDD; cd00063; FN3; 2.
DR CDD; cd05065; PTKc_EphR_B; 1.
DR Gene3D; 2.60.40.1770; ephrin a2 ectodomain; 1.
DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1.
DR Gene3D; 2.60.40.10; Immunoglobulins; 2.
DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 1.
DR InterPro; IPR027936; Eph_TM.
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; 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; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016257; Tyr_kinase_ephrin_rcpt.
DR PANTHER; PTHR46877; EPH RECEPTOR A5; 1.
DR PANTHER; PTHR46877:SF11; EPHRIN TYPE-B RECEPTOR 2; 1.
DR Pfam; PF14575; EphA2_TM; 1.
DR Pfam; PF01404; Ephrin_lbd; 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; SM01411; Ephrin_rec_like; 1.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49265; Fibronectin type III; 1.
DR SUPFAM; SSF49785; Galactose-binding domain-like; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR SUPFAM; SSF47769; SAM/Pointed domain; 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; PS50105; SAM_DOMAIN; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Disulfide bond; Kinase; Membrane;
KW Nucleotide-binding; Receptor; Reference proteome; Repeat; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..976
FT /note="Ephrin type-B receptor 4b"
FT /evidence="ECO:0000255"
FT /id="PRO_5004160543"
FT TOPO_DOM 24..541
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 542..562
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 563..976
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 25..204
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 326..434
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 438..529
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 613..897
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 906..970
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT ACT_SITE 738
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 619..627
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 645
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DISULFID 69..186
FT /evidence="ECO:0000250|UniProtKB:P54760"
FT DISULFID 103..113
FT /evidence="ECO:0000250|UniProtKB:P54760"
FT CONFLICT 173..174
FT /note="KK -> LF (in Ref. 1; CAA06302)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="S -> C (in Ref. 1; CAA06302)"
FT /evidence="ECO:0000305"
FT CONFLICT 299
FT /note="F -> S (in Ref. 1; CAA06302 and 3; AAI63275)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="P -> S (in Ref. 1; CAA06302 and 3; AAI63275)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 976 AA; 108231 MW; 76F34B36F820B2E1 CRC64;
MDRVCWIMAL SWFWMVSTGL VSAEEEVLMN TKLETSDLRW TIYPSGDPEW EEMSGLDEEG
NSVRTFQVCP MDSSVSHWLR TRFIPRHGAS QVYVEIRFTM MECSAMPASF RTCKETFNLY
YYQSDEDTAS ATHPAWMENP YSKVDTVAAD FLLRRGGERK SNVKTVRVGP LSKKGFYLAF
QTQGACMALL SVRVFFKKCP AVSRAFSSFP ETLPHSLVQQ AEGVCVDNSA PTGQSTAPPT
MFCGEDGQWV GPPSSTCACK PGYEPVDSDR CRACGLGQYK ASVGGSLCRV CPDNSNTHFA
GSSLCVCRPG YHRATSDLPD SACTKPPSAP RSIIYQINDT VVTLEWSEPL DRGGRSDLSY
SVECMHCRGS LCVQCADSIT YRPGQMGVPG RRVIIRGLLP HTTYTFTVLA QNGVSAVSHT
SPASSSVNIT TSRDVAVPVS GIRRIKASES SVSISWTVPP QTQHSIQDYQ LRYSLKGQDD
GWQYVSSRSS SVVLNDLSRA SQYQVQVRAR TAAGYGHFSS AVSISTLPDD EESPSRLMLT
GVLVAIGLLI LIAVVIVAVF CFRRSTRRRD PDPDKSGQFL MGQGIKVYID PFTYEDPNEA
VREFAKEIDV SFVKIEEVIG AGEFGEVCRG RLKVPGKKEN YVAIKTLKGG YTDKQRRDFL
SEASIMGQFQ HPNIIHLEGV ITASCPVMIL TEYMENGALD SFLRLNDGQF TPIQLVGMLR
GIASGMKYLS EMSFVHRDLA ARNILVNSNL VCKVSDFGLS RFLTENSSDP TYTSSLGGKI
PIRWTAPEAI AFRKFTSASD VWSYGIVMWE VMSFGERPYW DMSNQDVINA IEQDYRLPPP
PECPASLHQL MLDCWQKERS SRPRFCAIVS ALDRLIRNPA SLKITGRIPD GPSHPLLDQR
APPPLSHCSS VADWLRAIKM ERYEDAFMQA GFTAIQHITH ISTEDLLRIG VTLAGHQKKI
LSSVQTLRIH GGSLRY
//
