EPA4B_XENLA
ID EPA4B_XENLA Reviewed; 985 AA.
AC Q91694;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Ephrin type-A receptor 4-B;
DE EC=2.7.10.1;
DE AltName: Full=Pagliaccio;
DE AltName: Full=Tyrosine-protein kinase receptor PAG;
DE Flags: Precursor;
GN Name=epha4-b; Synonyms=pag;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Neural crest;
RX PubMed=7918105; DOI=10.1016/0925-4773(94)90072-8;
RA Winning R.S., Sargent T.D.;
RT "Pagliaccio, a member of the Eph family of receptor tyrosine kinase genes,
RT has localized expression in a subset of neural crest and neural tissues in
RT Xenopus laevis embryos.";
RL Mech. Dev. 46:219-229(1994).
CC -!- FUNCTION: Receptor tyrosine kinase which binds membrane-bound ephrin
CC family ligands residing on adjacent cells, leading to contact-dependent
CC bidirectional signaling into neighboring cells. The signaling pathway
CC downstream of the receptor is referred to as forward signaling while
CC the signaling pathway downstream of the ephrin ligand is referred to as
CC reverse signaling. Highly promiscuous, it has the unique property among
CC Eph receptors to bind and to be physiologically activated by both GPI-
CC anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1
CC and EFNB3. Upon activation by ephrin ligands, modulates cell morphology
CC and integrin-dependent cell adhesion through regulation of the Rac, Rap
CC and Rho GTPases activity. Plays an important role in the development of
CC the nervous system controlling different steps of axonal guidance
CC including the establishment of the corticospinal projections (By
CC 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 -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Early endosome {ECO:0000250}.
CC Note=Clustered upon activation and targeted to early endosome.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Localized expression in a subset of neural crest
CC and neural tissues in embryos.
CC -!- DEVELOPMENTAL STAGE: Present transiently in visceral arch 3. Also
CC expressed in the forebrain, rhombomeres R3 and R5 of the hindbrain and
CC in the pronephros.
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; L26099; AAA64464.1; -; mRNA.
DR PIR; I51549; I51549.
DR AlphaFoldDB; Q91694; -.
DR SMR; Q91694; -.
DR BRENDA; 2.7.10.1; 6725.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
DR CDD; cd10482; EphR_LBD_A4; 1.
DR CDD; cd00063; FN3; 2.
DR CDD; cd09545; SAM_EPH-A4; 1.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034270; EphA4_rcpt_lig-bd.
DR InterPro; IPR030602; EphA4_SAM.
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; 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; PF00041; fn3; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF07647; SAM_2; 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; SM00220; S_TKc; 1.
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 2: Evidence at transcript level;
KW ATP-binding; Cell adhesion; Cell membrane; Developmental protein; Endosome;
KW Glycoprotein; Kinase; Membrane; Neurogenesis; Nucleotide-binding;
KW Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..985
FT /note="Ephrin type-A receptor 4-B"
FT /id="PRO_0000016811"
FT TOPO_DOM 21..547
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 548..569
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 570..985
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..209
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 328..438
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 439..536
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 620..881
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 910..974
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT MOTIF 983..985
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 745
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 626..634
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 652
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 595
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 601
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 778
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 927
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 407
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 985 AA; 109730 MW; B6CFD128ACB64DF0 CRC64;
MAGIVHGILF CGLFGLCWAV TGSRIYPASE VTLLDSRSVQ GELGWIASPL EGGWEEVSIM
DEKNTPIRTY QVCNVMESSQ NNWLRTDWIP RSGAQRVYVE IKFTLRDCNS LPGVMGTCKE
TFNLYYYESN NDKERFIRET QYVKIDTIAA DESFTQVDIG DRIMKLNTEV RDVGPLSKKG
FYLAFQDVGA CIALVSVRVF YKKCPLTVRN LAQFPDTITG SDTSSLVEVR GSCVDNSEEK
DVPKMYCGAD GEWLVPIGNC LCNAGFEEHN GGCQACKVGY YKALSTDAAC SKCPPHSYAL
REGSTSCTCD RGYFRADTDP ASMPCTRPPS APQNLISNVN ETSVNLEWSP PQNSGGRPDV
SYNLVCKRCG SDLTRCSPCG SGVHYSPQQN GLKTTKVSIN DLQAHTNYTF EVWAINGVSK
QNPEQDQAVS VTVTTNQAAP STVTQIQPKE ITRHSVSLTW PEPERANGVI LEYEVKYYEK
DQNERSYRIV KTASRSADIK GLNPLTGYVF HVRARTAAGY GEFSGPFEFT TNTVPSPMIG
EGTSPTVLLV SVAGSIVLVV ILIAAFVISR RRSKYSKAKQ EADEEKHLNQ GVKTYVDPFT
YEDPNQAVRE FAKEIDASCI KIEKVIGVGE FGEVCSGRLK VPGKREIYVA IKTLKAGYTD
KQRRDFLSEA SIMGQFDHPN IIHLEGVVTK CKPVMIITEY MENGSLDAFL RKNDGRFTVI
QLVGMLRGIG SGMKYLSDMS YVHRDLAARN ILVNSNLVCK VSDFGMSRVL EDDPEAAYTT
RGGKIPIRWT APEAIAYRKF TSASDVWSYG IVMWEVMSYG ERPYWDMSNQ DVIKAIEEGY
RLPPPMDCPI ALHQLMLDCW QKDRSDRPKF GQIVSMLDKL IRNPNSLKRT GLENSRTNTA
LLDPSSPEWS QVASVLDWLQ ASKWKRYKDN FTAAGYTSLE AVVHVNQDDL TRIGISSPSH
QNKILSSVQG MRTQLQQMQG RMVPV
