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Ephrin type-A receptor 4-A (EC 2 7 10 1) (Tyrosine-protein kinase receptor SEK-1) (xSEK-1)

 EPA4A_XENLA             Reviewed;         986 AA.
Q91845;
30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
01-NOV-1996, sequence version 1.
05-DEC-2018, entry version 138.
RecName: Full=Ephrin type-A receptor 4-A;
EC=2.7.10.1;
AltName: Full=Tyrosine-protein kinase receptor SEK-1;
Short=xSEK-1;
Flags: Precursor;
Name=epha4-a; Synonyms=sek1;
Xenopus laevis (African clawed frog).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Amphibia; Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus;
Xenopus.
NCBI_TaxID=8355;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=8575301;
Xu Q., Alldus G., Holder N., Wilkinson D.G.;
"Expression of truncated Sek-1 receptor tyrosine kinase disrupts the
segmental restriction of gene expression in the Xenopus and zebrafish
hindbrain.";
Development 121:4005-4016(1995).
-!- FUNCTION: Receptor tyrosine kinase which binds membrane-bound
ephrin 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. Highly
promiscuous, it has the unique property among Eph receptors to
bind and to be physiologically activated by both GPI-anchored
ephrin-A and transmembrane ephrin-B ligands including EFNA1 and
EFNB3. Upon activation by ephrin ligands, modulates cell
morphology and integrin-dependent cell adhesion through regulation
of the Rac, Rap and Rho GTPases activity. Plays an important role
in the development of the nervous system controlling different
steps of axonal guidance including the establishment of the
corticospinal projections (By similarity). {ECO:0000250}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-
tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136,
Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216;
EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass
type I membrane protein {ECO:0000250}. Early endosome
{ECO:0000250}. Note=Clustered upon activation and targeted to
early endosome. {ECO:0000250}.
-!- DEVELOPMENTAL STAGE: Expression occurs in R3, R5 and transiently
at lower levels in R2.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
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EMBL; X91191; CAA62601.1; -; mRNA.
RefSeq; NP_001090183.1; NM_001096714.1.
UniGene; Xl.57159; -.
ProteinModelPortal; Q91845; -.
SMR; Q91845; -.
PRIDE; Q91845; -.
GeneID; 779062; -.
KEGG; xla:779062; -.
CTD; 779062; -.
Xenbase; XB-GENE-6253098; epha4.
HOVERGEN; HBG062180; -.
KO; K05105; -.
BRENDA; 2.7.10.1; 6725.
GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
GO; GO:0005005; F:transmembrane-ephrin receptor activity; ISS:UniProtKB.
GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
CDD; cd10482; EphR_LBD_A4; 1.
CDD; cd00063; FN3; 2.
Gene3D; 2.60.120.260; -; 1.
Gene3D; 2.60.40.10; -; 2.
InterPro; IPR027936; Eph_TM.
InterPro; IPR034270; EphA4_rcpt_lig-bd.
InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom.
InterPro; IPR003961; FN3_dom.
InterPro; IPR036116; FN3_sf.
InterPro; IPR008979; Galactose-bd-like_sf.
InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR001660; SAM.
InterPro; IPR013761; SAM/pointed_sf.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR011641; Tyr-kin_ephrin_A/B_rcpt-like.
InterPro; IPR008266; Tyr_kinase_AS.
InterPro; IPR020635; Tyr_kinase_cat_dom.
InterPro; IPR016257; Tyr_kinase_ephrin_rcpt.
InterPro; IPR001426; Tyr_kinase_rcpt_V_CS.
Pfam; PF14575; EphA2_TM; 1.
Pfam; PF01404; Ephrin_lbd; 1.
Pfam; PF00041; fn3; 2.
Pfam; PF07714; Pkinase_Tyr; 1.
Pfam; PF07647; SAM_2; 1.
PIRSF; PIRSF000666; TyrPK_ephrin_receptor; 1.
PRINTS; PR00109; TYRKINASE.
SMART; SM00615; EPH_lbd; 1.
SMART; SM01411; Ephrin_rec_like; 1.
SMART; SM00060; FN3; 2.
SMART; SM00220; S_TKc; 1.
SMART; SM00454; SAM; 1.
SMART; SM00219; TyrKc; 1.
SUPFAM; SSF47769; SSF47769; 1.
SUPFAM; SSF49265; SSF49265; 1.
SUPFAM; SSF49785; SSF49785; 1.
SUPFAM; SSF56112; SSF56112; 1.
SUPFAM; SSF57184; SSF57184; 1.
PROSITE; PS01186; EGF_2; 1.
PROSITE; PS51550; EPH_LBD; 1.
PROSITE; PS50853; FN3; 2.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PROSITE; PS00790; RECEPTOR_TYR_KIN_V_1; 1.
PROSITE; PS00791; RECEPTOR_TYR_KIN_V_2; 1.
PROSITE; PS50105; SAM_DOMAIN; 1.
2: Evidence at transcript level;
ATP-binding; Cell adhesion; Cell membrane; Developmental protein;
Endosome; Glycoprotein; Kinase; Membrane; Neurogenesis;
Nucleotide-binding; Phosphoprotein; Receptor; Repeat; Signal;
Transferase; Transmembrane; Transmembrane helix;
Tyrosine-protein kinase.
SIGNAL 1 20 {ECO:0000255}.
CHAIN 21 986 Ephrin type-A receptor 4-A.
/FTId=PRO_0000016810.
TOPO_DOM 21 547 Extracellular. {ECO:0000255}.
TRANSMEM 548 569 Helical. {ECO:0000255}.
TOPO_DOM 570 986 Cytoplasmic. {ECO:0000255}.
DOMAIN 30 209 Eph LBD. {ECO:0000255|PROSITE-
ProRule:PRU00883}.
DOMAIN 328 438 Fibronectin type-III 1.
{ECO:0000255|PROSITE-ProRule:PRU00316}.
DOMAIN 439 536 Fibronectin type-III 2.
{ECO:0000255|PROSITE-ProRule:PRU00316}.
DOMAIN 620 881 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
DOMAIN 911 975 SAM. {ECO:0000255|PROSITE-
ProRule:PRU00184}.
NP_BIND 626 634 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOTIF 984 986 PDZ-binding. {ECO:0000255}.
COMPBIAS 191 325 Cys-rich.
ACT_SITE 745 745 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10028}.
BINDING 652 652 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 595 595 Phosphotyrosine; by autocatalysis.
{ECO:0000250}.
MOD_RES 601 601 Phosphotyrosine; by autocatalysis.
{ECO:0000250}.
MOD_RES 778 778 Phosphotyrosine; by autocatalysis.
{ECO:0000255}.
MOD_RES 928 928 Phosphotyrosine; by autocatalysis.
{ECO:0000255}.
CARBOHYD 340 340 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 407 407 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
SEQUENCE 986 AA; 109841 MW; C34F4078DB3F025F 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 SDLTRCRPCG SGVHYSPQQN GLKTTKVSIT DLQAHTNYTF EVWSINGVSK
QNPGQDQAVS VTVTTNQAAP STVTQIQPKD ITRHSVSLTW PEPERPNGVI LEYEVKYYEK
DQNERTYRIV KTTSRSADIK GLNPLTAYVF HVRARTAAGY GEFSGPFEFT TNTVPSPMIG
EGASPTVLLV SVAGSIVLVV ILIAAFVISR RRSKYSKAKQ EADEEKHLNQ GVKTYVDPFT
YEDPNQAVRE FAKEIDASCI KIEKVIGVGE FGEVCSGRLK VPGKREIYVA IKTLKAGYTD
KQRRDFLSEA SIMGQFDHPN IIHLEGVVTK CKPVMIITEY MENGSLDAFL RKNDGRFTVI
QLVGILRGIG SGMKYLSDMS YVHRDLAARN ILVNSNLVCK VSDFGMSRVL EDDPEAAYTT
RGGKIPIRWT APEAIAYRKF TSASDVWSYG IVMWEVMSYG ERPYWDMSNQ DVIKAIEEGY
RLPPPMDCPI ALHQLMLDCW QKERSDRPKF GQIVSMLDKL IRNPNSLKRT GLDNSSRTNT
TLLDPSSPEW SQVASVLDWL QAIKMERYKD NFTAAGYTSL EAVVHVNQDD LTRIGISSPS
HQNKILSSVQ GMRTQMQQIQ GRMVPV


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