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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-JUN-2019, entry version 141.
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.
SMR; Q91845; -.
PRIDE; Q91845; -.
GeneID; 779062; -.
KEGG; xla:779062; -.
CTD; 779062; -.
Xenbase; XB-GENE-6253098; epha4.
KO; K05105; -.
OrthoDB; 933071at2759; -.
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; 1.10.150.50; -; 1.
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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WP1004: Kit Receptor Signaling Pathway
WP258: TGF-beta Receptor Signaling Pathway
WP774: Kit Receptor Signaling Pathway
WP2197: Endothelin
WP926: TGF-beta Receptor Signaling Pathway
WP57: Signal Transduction of S1P Receptor
WP94: Signaling of Hepatocyte Growth Factor Receptor
WP1249: EPO Receptor Signaling
WP1918: Signaling by Robo receptor
WP274: B Cell Receptor Signaling Pathway
WP1046: Signaling of Hepatocyte Growth Factor Receptor
WP313: Signaling of Hepatocyte Growth Factor Receptor
WP810: Signaling of Hepatocyte Growth Factor Receptor
WP1112: EPO Receptor Signaling
WP1493: Carbon assimilation C4 pathway
WP23: B Cell Receptor Signaling Pathway
WP590: Cardiovascular Signaling
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Related Genes :
[Epha4 Sek Sek1] Ephrin type-A receptor 4 (EC 2.7.10.1) (Tyrosine-protein kinase receptor MPK-3) (Tyrosine-protein kinase receptor SEK-1)
[EPHA4 HEK8 SEK TYRO1] Ephrin type-A receptor 4 (EC 2.7.10.1) (EPH-like kinase 8) (EK8) (hEK8) (Tyrosine-protein kinase TYRO1) (Tyrosine-protein kinase receptor SEK)
[Epha2 Eck Myk2 Sek2] Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK) (Tyrosine-protein kinase receptor MPK-5) (Tyrosine-protein kinase receptor SEK-2)
[Ephb2 Epth3 Nuk Sek3] Ephrin type-B receptor 2 (EC 2.7.10.1) (Neural kinase) (Nuk receptor tyrosine kinase) (Tyrosine-protein kinase receptor EPH-3) (Tyrosine-protein kinase receptor SEK-3) [Cleaved into: EphB2/CTF1; EphB2/CTF2]
[EPHA2 ECK] Ephrin type-A receptor 2 (EC 2.7.10.1) (Epithelial cell kinase) (Tyrosine-protein kinase receptor ECK)
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[EPHB4 HTK MYK1 TYRO11] Ephrin type-B receptor 4 (EC 2.7.10.1) (Hepatoma transmembrane kinase) (Tyrosine-protein kinase TYRO11)
[NTRK1 MTC TRK TRKA] High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1) (TRK1-transforming tyrosine kinase protein) (Tropomyosin-related kinase A) (Tyrosine kinase receptor) (Tyrosine kinase receptor A) (Trk-A) (gp140trk) (p140-TrkA)
[Ephb1 Elk Epth2] Ephrin type-B receptor 1 (EC 2.7.10.1) (ELK) (Tyrosine-protein kinase receptor EPH-2)
[Epha7 Ebk Ehk3 Mdk1] Ephrin type-A receptor 7 (EC 2.7.10.1) (Developmental kinase 1) (mDK-1) (EPH homology kinase 3) (EHK-3) (Embryonic brain kinase) (EBK)
[EPHA4 CEK8] Ephrin type-A receptor 4 (EC 2.7.10.1) (EPH-like kinase 8) (EK8) (cEK8)
[DDR1 CAK EDDR1 NEP NTRK4 PTK3A RTK6 TRKE] Epithelial discoidin domain-containing receptor 1 (Epithelial discoidin domain receptor 1) (EC 2.7.10.1) (CD167 antigen-like family member A) (Cell adhesion kinase) (Discoidin receptor tyrosine kinase) (HGK2) (Mammary carcinoma kinase 10) (MCK-10) (Protein-tyrosine kinase 3A) (Protein-tyrosine kinase RTK-6) (TRK E) (Tyrosine kinase DDR) (Tyrosine-protein kinase CAK) (CD antigen CD167a)
[Ntrk1 Trk Trka] High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1) (Slow nerve growth factor receptor) (p140-TrkA) (Trk-A)
[Tek Hyk Tie-2 Tie2] Angiopoietin-1 receptor (EC 2.7.10.1) (Endothelial tyrosine kinase) (HYK) (STK1) (Tunica interna endothelial cell kinase) (Tyrosine kinase with Ig and EGF homology domains-2) (Tyrosine-protein kinase receptor TEK) (Tyrosine-protein kinase receptor TIE-2) (mTIE2) (p140 TEK) (CD antigen CD202b)
[kdrl flk flk-1 flk1 flka kdr kdra vegfr2 vegfr4 vegr2 si:ch211-276g21.4] Vascular endothelial growth factor receptor kdr-like (EC 2.7.10.1) (Fetal liver kinase 1) (FLK-1) (Kinase insert domain receptor-A) (Kinase insert domain receptor-like) (Protein-tyrosine kinase receptor flk-1) (Vascular endothelial growth factor receptor 4) (VEGFR-4)
[EPHA2] Ephrin type-A receptor 2 (EC 2.7.10.1)
[] Genome polyprotein [Cleaved into: Leader protease (Lpro) (EC 3.4.22.46); Protein VP0 (VP4-VP2); Protein VP4 (P1A) (Virion protein 4); Protein VP2 (P1B) (Virion protein 2); Protein VP3 (P1C) (Virion protein 3); Protein VP1 (P1D) (Virion protein 1); Protein 2A (P2A) (P52); Protein 2B (P2B); Protein 2C (P2C) (EC 3.6.1.15); Protein 3A (P3A); Protein 3B-1 (P3B-1) (Genome-linked protein VPg1); Protein 3B-2 (P3B-2) (Genome-linked protein VPg2); Protein 3B-3 (P3B-3) (Genome-linked protein VPg3); Protease 3C (EC 3.4.22.28) (Picornain 3C) (P3C) (Protease P20B); RNA-directed RNA polymerase 3D-POL (P3D-POL) (EC 2.7.7.48) (P56A)]
[NTRK2 TRKB] BDNF/NT-3 growth factors receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 2) (TrkB tyrosine kinase) (Trk-B)
[FLT4 VEGFR3] Vascular endothelial growth factor receptor 3 (VEGFR-3) (EC 2.7.10.1) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4)
[Flt4 Flt-4 Vegfr3] Vascular endothelial growth factor receptor 3 (VEGFR-3) (EC 2.7.10.1) (Fms-like tyrosine kinase 4) (FLT-4) (Tyrosine-protein kinase receptor FLT4)
[ERBB4 HER4] Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) (Tyrosine kinase-type cell surface receptor HER4) (p180erbB4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)]
[Ros1 Ros Ros-1] Proto-oncogene tyrosine-protein kinase ROS (EC 2.7.10.1) (Proto-oncogene c-Ros) (Proto-oncogene c-Ros-1) (Receptor tyrosine kinase c-ros oncogene 1) (c-Ros receptor tyrosine kinase)
[Fgfr4 Fgfr-4 Mpk-11] Fibroblast growth factor receptor 4 (FGFR-4) (EC 2.7.10.1) (Protein-tyrosine kinase receptor MPK-11) (CD antigen CD334)
[Ntrk1] High affinity nerve growth factor receptor (EC 2.7.10.1) (Neurotrophic tyrosine kinase receptor type 1)
[Ephb1] Ephrin type-B receptor 1 (EC 2.7.10.1)
[Or22b AN12 DOR22A.2 dor67 Or22A.2 CG4231] Odorant receptor 22b
[FLT3 CD135 FLK2 STK1] Receptor-type tyrosine-protein kinase FLT3 (EC 2.7.10.1) (FL cytokine receptor) (Fetal liver kinase-2) (FLK-2) (Fms-like tyrosine kinase 3) (FLT-3) (Stem cell tyrosine kinase 1) (STK-1) (CD antigen CD135)
[Erbb4 Mer4] Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)]

Bibliography :