EPHA7_RAT
ID EPHA7_RAT Reviewed; 998 AA.
AC P54759;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Ephrin type-A receptor 7;
DE EC=2.7.10.1;
DE AltName: Full=EPH homology kinase 3;
DE Short=EHK-3;
DE Flags: Precursor;
GN Name=Epha7; Synonyms=Ehk-3, Ehk3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RX PubMed=7731712;
RA Valenzuela D.M., Rojas E., Griffiths J.A., Compton D.L., Gisser M.,
RA Ip N.Y., Goldfarb M., Yancopoulos G.D.;
RT "Identification of full-length and truncated forms of Ehk-3, a novel member
RT of the Eph receptor tyrosine kinase family.";
RL Oncogene 10:1573-1580(1995).
RN [2]
RP FUNCTION IN APOPTOSIS.
RX PubMed=16983667; DOI=10.1002/jnr.21048;
RA Figueroa J.D., Benton R.L., Velazquez I., Torrado A.I., Ortiz C.M.,
RA Hernandez C.M., Diaz J.J., Magnuson D.S., Whittemore S.R., Miranda J.D.;
RT "Inhibition of EphA7 up-regulation after spinal cord injury reduces
RT apoptosis and promotes locomotor recovery.";
RL J. Neurosci. Res. 84:1438-1451(2006).
CC -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously GPI-
CC anchored ephrin-A family ligands residing on adjacent cells, leading to
CC contact-dependent bidirectional signaling into neighboring cells. The
CC signaling pathway downstream of the receptor is referred to as forward
CC signaling while the signaling pathway downstream of the ephrin ligand
CC is referred to as reverse signaling. Among GPI-anchored ephrin-A
CC ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their
CC interaction regulates brain development modulating cell-cell adhesion
CC and repulsion. Has a repellent activity on axons and is for instance
CC involved in the guidance of corticothalamic axons and in the proper
CC topographic mapping of retinal axons to the colliculus. May also
CC regulate brain development through a caspase(CASP3)-dependent
CC proapoptotic activity. Forward signaling may result in activation of
CC components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1
CC AND MAPK3 which are phosphorylated upon activation of EPHA7.
CC {ECO:0000269|PubMed:16983667}.
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 -!- 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 (By similarity).
CC Interacts (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain)
CC (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P54759-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P54759-2; Sequence=VSP_003012;
CC -!- TISSUE SPECIFICITY: Restricted to the nervous system.
CC -!- PTM: Phosphorylated. {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform Long]: More widely expressed in the embryo.
CC -!- MISCELLANEOUS: [Isoform Short]: Lacks the kinase domain. {ECO:0000305}.
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; U21954; AAA86830.1; -; mRNA.
DR EMBL; U21955; AAA86831.1; -; mRNA.
DR RefSeq; NP_599158.1; NM_134331.1. [P54759-1]
DR RefSeq; XP_006238026.1; XM_006237964.3.
DR AlphaFoldDB; P54759; -.
DR SMR; P54759; -.
DR BioGRID; 251168; 2.
DR IntAct; P54759; 3.
DR STRING; 10116.ENSRNOP00000009899; -.
DR GlyGen; P54759; 2 sites.
DR iPTMnet; P54759; -.
DR PhosphoSitePlus; P54759; -.
DR PaxDb; P54759; -.
DR PRIDE; P54759; -.
DR GeneID; 171287; -.
DR KEGG; rno:171287; -.
DR UCSC; RGD:70957; rat. [P54759-1]
DR CTD; 2045; -.
DR RGD; 70957; Epha7.
DR VEuPathDB; HostDB:ENSRNOG00000007030; -.
DR eggNOG; KOG0196; Eukaryota.
DR HOGENOM; CLU_000288_141_0_1; -.
DR InParanoid; P54759; -.
DR OMA; ETDYNTG; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; P54759; -.
DR TreeFam; TF315608; -.
DR BRENDA; 2.7.10.1; 5301.
DR Reactome; R-RNO-2682334; EPH-Ephrin signaling.
DR Reactome; R-RNO-3928663; EPHA-mediated growth cone collapse.
DR Reactome; R-RNO-3928665; EPH-ephrin mediated repulsion of cells.
DR PRO; PR:P54759; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000007030; Expressed in frontal cortex and 16 other tissues.
DR Genevisible; P54759; RN.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0031594; C:neuromuscular junction; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:RGD.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008046; F:axon guidance receptor activity; ISS:UniProtKB.
DR GO; GO:0045499; F:chemorepellent activity; ISS:UniProtKB.
DR GO; GO:0005003; F:ephrin receptor activity; NAS:RGD.
DR GO; GO:0046875; F:ephrin receptor binding; IDA:RGD.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
DR GO; GO:0019838; F:growth factor binding; ISO:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR GO; GO:0048755; P:branching morphogenesis of a nerve; ISS:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0050919; P:negative chemotaxis; ISS:UniProtKB.
DR GO; GO:0048671; P:negative regulation of collateral sprouting; ISO:RGD.
DR GO; GO:0051964; P:negative regulation of synapse assembly; ISO:RGD.
DR GO; GO:0072178; P:nephric duct morphogenesis; ISO:RGD.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0022407; P:regulation of cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0043281; P:regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0050730; P:regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0099175; P:regulation of postsynapse organization; ISO:RGD.
DR GO; GO:0031952; P:regulation of protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0031290; P:retinal ganglion cell axon guidance; ISO:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd10485; EphR_LBD_A7; 1.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR034283; EphA7_rcpt_lig-bd.
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; PF00536; SAM_1; 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; 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 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; ATP-binding; Cell membrane;
KW Developmental protein; Glycoprotein; Kinase; Membrane; Neurogenesis;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..998
FT /note="Ephrin type-A receptor 7"
FT /id="PRO_0000016820"
FT TOPO_DOM 28..555
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 556..576
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 577..998
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..210
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 331..441
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 442..537
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 633..894
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 923..987
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT MOTIF 996..998
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT ACT_SITE 758
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 639..647
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 665
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 608
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 614
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 791
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 940
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT CARBOHYD 343
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 410
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 600..610
FT /note="FKFPGTKTYID -> SLVTNEHLSVL (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:7731712"
FT /id="VSP_003012"
SQ SEQUENCE 998 AA; 111953 MW; A7A82A698924876C CRC64;
MVVQTRYPSW IILCYIWLLG FAHTGEAQAA KEVLLLDSKA QQTELEWISS PPSGWEEISG
LDENYTPIRT YQVCQVMEPN QNNWLRTNWI SKGNAQRIFV ELKFTLRDCN SLPGVLGTCK
ETFNLYYYET DYDTGRNIRE NLYVKIDTIA ADESFTQGDL GERKMKLNTE VREIGPLSKK
GFYLAFQDVG ACIALVSVKV YYKKCWSIIE NLAVFPDTVT GSEFSSLVEV RGTCVSSAEE
EAENSPRMHC SAEGEWLVPI GKCICKAGYQ QKGDTCEPCG RRFYKSSSQD LQCSRCPTHS
FSDREGSSRC ECEDGYYRAP SDPPYVACTR PPSAPQNLIF NINQTTVSLE WSPPADNGGR
NDVTYRILCK RCSWEQGECV PCGSNIGYMP QQTGLEDNYV TVMDLLAHAN YTFEVEAVNG
VSDLSRSQRL FAAVSITTGQ AAPSQVSGVM KERVLQRSVE LSWQEPEHPN GVITEYEIKY
YEKDQRERTY STLKTKSTSA SINNLKPGTV YVFQIRAFTA AGYGNYSPRL DVATLEEASG
KMFEATAVSS EQNPVIIIAV VAVAGTIILV FMVFGFIIGR RHCGYSKADQ EGDEELYFHF
KFPGTKTYID PETYEDPNRA VHQFAKELDA SCIKIERVIG AGEFGEVCSG RLKLPGKRDV
AVAIKTLKVG YTEKQRRDFL CEASIMGQFD HPNVVHLEGV VTRGKPVMIV IEFMENGALD
AFLRKHDGQF TVIQLVGMLR GIAAGMRYLA DMGYVHRDLA ARNILVNSNL VCKVSDFGLS
RVIEDDPEAV YTTTGGKIPV RWTAPEAIQY RKFTSASDVW SYGIVMWEVM SYGERPYWDM
SNQDVIKAIE EGYRLPAPMD CPAGLHQLML DCWQKERAER PKFEQIVGIL DKMIRNPSSL
KTPLGTCSRP ISPLLDQSTP DFTAFCSVGE WLQAIKMERY KDNFTAAGYN SLESVARMTI
DDVMSLGITL VGHQKKIMSS IQTMRAQMLH LHGTGIQV
