ID A0A6J0B1H8_VICPA Unreviewed; 995 AA.
AC A0A6J0B1H8;
DT 07-OCT-2020, integrated into UniProtKB/TrEMBL.
DT 07-OCT-2020, sequence version 1.
DT 28-JAN-2026, entry version 26.
DE RecName: Full=Ephrin type-B receptor 4 {ECO:0000256|ARBA:ARBA00070273};
DE EC=2.7.10.1 {ECO:0000256|ARBA:ARBA00011902};
DE AltName: Full=Hepatoma transmembrane kinase {ECO:0000256|ARBA:ARBA00076055};
GN Name=EPHB4 {ECO:0000313|RefSeq:XP_015107454.1};
OS Vicugna pacos (Alpaca) (Lama pacos).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Tylopoda; Camelidae; Vicugna.
OX NCBI_TaxID=30538 {ECO:0000313|Proteomes:UP001652581, ECO:0000313|RefSeq:XP_015107454.1};
RN [1] {ECO:0000313|RefSeq:XP_015107454.1}
RP IDENTIFICATION.
RG RefSeq;
RL Submitted (AUG-2025) to UniProtKB.
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 it is involved in the regulation
CC of cell adhesion and 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.
CC {ECO:0000256|ARBA:ARBA00059980}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] +
CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000256|ARBA:ARBA00051243};
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. Interacts with RASA1;
CC the interaction depends on EPHB4 tyrosine-phosphorylation.
CC {ECO:0000256|ARBA:ARBA00065958}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004251};
CC Single-pass type I membrane protein {ECO:0000256|ARBA:ARBA00004251}.
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DR RefSeq; XP_015107454.1; XM_015251968.3.
DR AlphaFoldDB; A0A6J0B1H8; -.
DR FunCoup; A0A6J0B1H8; 1225.
DR GeneID; 102535893; -.
DR CTD; 2050; -.
DR InParanoid; A0A6J0B1H8; -.
DR OrthoDB; 4062651at2759; -.
DR Proteomes; UP001652581; Chromosome 18.
DR GO; GO:0030425; C:dendrite; IEA:TreeGrafter.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IEA:TreeGrafter.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-ARBA.
DR GO; GO:0007411; P:axon guidance; IEA:TreeGrafter.
DR CDD; cd10474; EphR_LBD_B4; 1.
DR CDD; cd00063; FN3; 2.
DR CDD; cd05065; PTKc_EphR_B; 1.
DR CDD; cd09554; SAM_EPH-B4; 1.
DR FunFam; 1.10.150.50:FF:000001; Ephrin type-A receptor 5; 1.
DR FunFam; 2.10.50.10:FF:000001; Ephrin type-A receptor 5; 1.
DR FunFam; 3.30.200.20:FF:000001; Ephrin type-A receptor 5; 1.
DR FunFam; 2.60.40.10:FF:000059; Ephrin type-A receptor 6; 1.
DR FunFam; 1.10.510.10:FF:000015; Ephrin type-B receptor 2; 1.
DR FunFam; 2.60.120.260:FF:000071; Ephrin type-B receptor 4; 1.
DR FunFam; 2.60.40.10:FF:000787; ephrin type-B receptor 4; 1.
DR FunFam; 2.60.40.1770:FF:000003; ephrin type-B receptor 4; 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; 3.30.200.20; Phosphorylase Kinase, domain 1; 1.
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; IPR037636; EPH-B4_SAM.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034290; EphB4_rcpt_lig-bd.
DR InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom.
DR InterPro; IPR050449; Ephrin_rcpt_TKs.
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 PANTHER; PTHR46877; EPH RECEPTOR A5; 1.
DR PANTHER; PTHR46877:SF19; RECEPTOR PROTEIN-TYROSINE KINASE; 1.
DR Pfam; PF14575; EphA2_TM; 1.
DR Pfam; PF25599; Ephrin_CRD; 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; 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; SSF57184; Growth factor receptor domain; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR SUPFAM; SSF47769; SAM/Pointed domain; 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 4: Predicted;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PIRSR:PIRSR000666-
KW 2}; Cell membrane {ECO:0000256|ARBA:ARBA00022475};
KW Disulfide bond {ECO:0000256|ARBA:ARBA00023157,
KW ECO:0000256|PIRSR:PIRSR000666-3};
KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW Kinase {ECO:0000256|ARBA:ARBA00022777};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741,
KW ECO:0000256|PIRSR:PIRSR000666-2};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW Receptor {ECO:0000256|ARBA:ARBA00023170,
KW ECO:0000313|RefSeq:XP_015107454.1};
KW Reference proteome {ECO:0000313|Proteomes:UP001652581};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|SAM:SignalP};
KW Transferase {ECO:0000256|ARBA:ARBA00022679};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW ECO:0000256|SAM:Phobius};
KW Tyrosine-protein kinase {ECO:0000256|ARBA:ARBA00023137}.
FT SIGNAL 1..15
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 16..995
FT /note="Ephrin type-B receptor 4"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5026672942"
FT TRANSMEM 546..571
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 17..202
FT /note="Eph LBD"
FT /evidence="ECO:0000259|PROSITE:PS51550"
FT DOMAIN 323..432
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000259|PROSITE:PS50853"
FT DOMAIN 436..537
FT /note="Fibronectin type-III"
FT /evidence="ECO:0000259|PROSITE:PS50853"
FT DOMAIN 623..907
FT /note="Protein kinase"
FT /evidence="ECO:0000259|PROSITE:PS50011"
FT DOMAIN 915..979
FT /note="SAM"
FT /evidence="ECO:0000259|PROSITE:PS50105"
FT REGION 974..995
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 748
FT /note="Proton acceptor"
FT /evidence="ECO:0000256|PIRSR:PIRSR000666-1"
FT BINDING 629..637
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000666-2"
FT BINDING 655
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR000666-2,
FT ECO:0000256|PROSITE-ProRule:PRU10141"
FT DISULFID 61..184
FT /evidence="ECO:0000256|PIRSR:PIRSR000666-3"
FT DISULFID 97..107
FT /evidence="ECO:0000256|PIRSR:PIRSR000666-3"
SQ SEQUENCE 995 AA; 109317 MW; 903C0B56F336B709 CRC64;
MELRALLCWA SLAAALEETL LNTKLETADL KWVTFPQEEG QWEELSGLDE EQHSVRTYEV
CDMQRAPGVA HWLRTGWVPR RGAVHVYATL RFTMLECLSL PQAGRSCKET FTVFYFESDA
DTATAHTPAW MENPYIKVDT VAAEHLTRKR PGAEATGKVN IKTLRLGPLT KAGFYLAFQD
QGACMALLSL HLFYKKCAQL TVNLTRFPET VPRELVVPVA GSCVADAVPG RGPSPSLYCR
EDGQWAEQPV TGCSCAQGFE AAEGNTRCRA CAQGTFKPLS GEGSCQPCPA NSHSNTIGSP
ICQCRIGYFR ARTDPRGAPC TTPPSAPRSV VPRLNGSSLR LEWSAPLESG GREDLTYALR
CRECRPGGSC TPCGGDLTFD PGPRDLVEPW VAIRGLRPDF TYTFEVTALN GVSSLASGPV
PFEAVNVTTD REVPPPVSDI RVTRSSPSSL SLAWAVPRAP SGAVLDYEVK YHEKPAPSLP
EQGAEGPSSV RFLKTSENRA ELRGLKRGAS YLVQVRARSE AGYGPFGQEH HSQTQLDENE
SWREQLALIA GTAVVGVVLV LVVVVIAVLC LRKQSNGREA EYSDKHGQYL IGHGTKVYID
PFTYEDPNEA VREFAKEIDV SYVKIEEVIG AGEFGEVCRG RLKAPGKKES CVAIKTLKGG
YTERQRREFL SEASIMGQFE HPNIIRLEGV VTNSVPVMIL TEFMENGALD SFLRLNDGQF
TVIQLVGMLR GIASGMRYLA EMSYVHRDLA ARNILVNSNL VCKVSDFGLS RFLEENSSDP
TYTSSLGGKI PIRWTAPEAI AFRKFTSASD AWSYGIVMWE VMSFGERPYW DMSNQDVINA
IEQDYRLPPP PDCPTSLHQL MLDCWQKDRN ARPRFPQVVS ALDKMIRNPA SLKIVARENG
GASHPLLDQR QPHYSAFGSV GEWLRAIKMG RYEESFAAAG FGSFELVSQI STEDLLRIGV
TLAGHQKKIL ASVQHMKSQA KPGAPGGSAA PAPQY
//
