EPHA5_RAT
ID EPHA5_RAT Reviewed; 1005 AA.
AC P54757;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Ephrin type-A receptor 5;
DE EC=2.7.10.1;
DE AltName: Full=EPH homology kinase 1;
DE Short=EHK-1;
DE Flags: Precursor;
GN Name=Epha5; Synonyms=Ehk-1, Ekh1, Rek7;
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 1; 2; 3; 4 AND 5).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=7504232;
RA Maisonpierre P.C., Barrezueta N.X., Yancopoulos G.D.;
RT "Ehk-1 and Ehk-2: two novel members of the Eph receptor-like tyrosine
RT kinase family with distinctive structures and neuronal expression.";
RL Oncogene 8:3277-3288(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=7898646; DOI=10.1016/0306-4522(94)90014-0;
RA Taylor V., Miescher G.C., Pfarr S., Honegger P., Breitschopf H.,
RA Lassmann H., Steck A.J.;
RT "Expression and developmental regulation of Ehk-1, a neuronal Elk-like
RT receptor tyrosine kinase in brain.";
RL Neuroscience 63:163-178(1994).
RN [3]
RP FUNCTION IN AXON GUIDANCE, AND SUBCELLULAR LOCATION.
RX PubMed=7748564; DOI=10.1016/0896-6273(95)90335-6;
RA Winslow J.W., Moran P., Valverde J., Shih A., Yuan J.Q., Wong S.C.,
RA Tsai S.P., Goddard A., Henzel W.J., Hefti F., Beck K.D., Caras I.W.;
RT "Cloning of AL-1, a ligand for an Eph-related tyrosine kinase receptor
RT involved in axon bundle formation.";
RL Neuron 14:973-981(1995).
RN [4]
RP FUNCTION IN SYNAPTIC PLASTICITY, AND TISSUE SPECIFICITY.
RX PubMed=9698392; DOI=10.1006/mcne.1998.0696;
RA Gao W.Q., Shinsky N., Armanini M.P., Moran P., Zheng J.L.,
RA Mendoza-Ramirez J.L., Phillips H.S., Winslow J.W., Caras I.W.;
RT "Regulation of hippocampal synaptic plasticity by the tyrosine kinase
RT receptor, REK7/EphA5, and its ligand, AL-1/Ephrin-A5.";
RL Mol. Cell. Neurosci. 11:247-259(1998).
RN [5]
RP FUNCTION IN SYNAPTOGENESIS, EFNA5 LIGAND-BINDING, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION.
RX PubMed=20824214; DOI=10.1371/journal.pone.0012486;
RA Akaneya Y., Sohya K., Kitamura A., Kimura F., Washburn C., Zhou R.,
RA Ninan I., Tsumoto T., Ziff E.B.;
RT "Ephrin-A5 and EphA5 interaction induces synaptogenesis during early
RT hippocampal development.";
RL PLoS ONE 5:E12486-E12486(2010).
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 most probably constitutes the cognate/functional ligand
CC for EPHA5. Functions as an axon guidance molecule during development
CC and may be involved in the development of the retinotectal, entorhino-
CC hippocampal and hippocamposeptal pathways. Together with EFNA5 plays
CC also a role in synaptic plasticity in adult brain through regulation of
CC synaptogenesis. In addition to its function in the nervous system, the
CC interaction of EPHA5 with EFNA5 mediates communication between
CC pancreatic islet cells to regulate glucose-stimulated insulin secretion
CC (By similarity). {ECO:0000250, ECO:0000269|PubMed:20824214,
CC ECO:0000269|PubMed:7748564, ECO:0000269|PubMed:9698392}.
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 SAM domain) with SAMD5 (via SAM domain) (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q60629}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20824214,
CC ECO:0000269|PubMed:7748564}; Single-pass type I membrane protein
CC {ECO:0000255}. Cell projection, axon {ECO:0000269|PubMed:20824214,
CC ECO:0000269|PubMed:7748564}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P54756}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P54757-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P54757-2; Sequence=VSP_003001;
CC Name=3;
CC IsoId=P54757-3; Sequence=VSP_003002;
CC Name=4;
CC IsoId=P54757-4; Sequence=VSP_003002, VSP_003003;
CC Name=5;
CC IsoId=P54757-5; Sequence=VSP_003001, VSP_003002, VSP_003003;
CC -!- TISSUE SPECIFICITY: Almost exclusively expressed in the nervous system.
CC Predominantly expressed in neurons. {ECO:0000269|PubMed:9698392}.
CC -!- PTM: Phosphorylated. Phosphorylation is stimulated by the ligand EFNA5.
CC Dephosphorylation upon stimulation by glucose, inhibits EPHA5 forward
CC signaling and results in insulin secretion (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION: [Isoform 3]:
CC Sequence=CAA55357.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X78689; CAA55357.1; ALT_FRAME; mRNA.
DR PIR; PT0186; PT0186.
DR PIR; S47489; S47489.
DR PIR; S49015; S49015.
DR PIR; S51603; S51603.
DR PIR; S51604; S51604.
DR RefSeq; NP_077343.1; NM_024367.1.
DR AlphaFoldDB; P54757; -.
DR SMR; P54757; -.
DR STRING; 10116.ENSRNOP00000002793; -.
DR BindingDB; P54757; -.
DR ChEMBL; CHEMBL4739679; -.
DR GuidetoPHARMACOLOGY; 1825; -.
DR GlyGen; P54757; 6 sites.
DR iPTMnet; P54757; -.
DR PhosphoSitePlus; P54757; -.
DR SwissPalm; P54757; -.
DR jPOST; P54757; -.
DR PaxDb; P54757; -.
DR PRIDE; P54757; -.
DR GeneID; 79208; -.
DR KEGG; rno:79208; -.
DR UCSC; RGD:620831; rat. [P54757-1]
DR CTD; 2044; -.
DR RGD; 620831; Epha5.
DR eggNOG; KOG0196; Eukaryota.
DR InParanoid; P54757; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; P54757; -.
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:P54757; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005912; C:adherens junction; ISO:RGD.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0071944; C:cell periphery; ISO:RGD.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005791; C:rough endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005003; F:ephrin receptor activity; IDA:UniProtKB.
DR GO; GO:0005004; F:GPI-linked ephrin receptor activity; ISS:UniProtKB.
DR GO; GO:0019838; F:growth factor binding; IPI:ARUK-UCL.
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; ISS:UniProtKB.
DR GO; GO:0019933; P:cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; ISO:RGD.
DR GO; GO:1904322; P:cellular response to forskolin; ISO:RGD.
DR GO; GO:0060997; P:dendritic spine morphogenesis; IDA:UniProtKB.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; ISS:UniProtKB.
DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:MGI.
DR GO; GO:0048666; P:neuron development; ISO:RGD.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0061178; P:regulation of insulin secretion involved in cellular response to glucose stimulus; ISS:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
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; 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; 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 Pfam; PF14575; EphA2_TM; 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; SM00060; FN3; 2.
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; 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; ATP-binding; Cell membrane; Cell projection;
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..26
FT /evidence="ECO:0000250"
FT CHAIN 27..1005
FT /note="Ephrin type-A receptor 5"
FT /id="PRO_0000016814"
FT TOPO_DOM 27..575
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 576..596
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 597..1005
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 62..240
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 359..469
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 470..564
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 677..938
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 967..1005
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 802
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 683..691
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 709
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 652
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 658
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 835
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 984
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 438
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 463
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT /id="VSP_003000"
FT VAR_SEQ 306..357
FT /note="VCRPGFFKASPHSQTCSKCPPHSYTHEEASTSCVCEKDYFRRESDPPTMACT
FT -> G (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:7504232"
FT /id="VSP_003001"
FT VAR_SEQ 358..470
FT /note="RPPSAPRNAISNVNETSVFLEWIPPADTGGGKDVSYYILCKKCNSHAGVCEE
FT CGGHVRYLPQQIGLKNTSVMMADPLAHTNYTFEIEAVNGVSDLSPGTRQYVSVNVTTNQ
FT AA -> T (in isoform 3, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:7504232,
FT ECO:0000303|PubMed:7898646"
FT /id="VSP_003002"
FT VAR_SEQ 597..621
FT /note="SGSCCECGCGRASSLCAVAHPSLIW -> R (in isoform 4 and
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:7504232"
FT /id="VSP_003003"
FT CONFLICT 170
FT /note="D -> E (in Ref. 2; CAA55357)"
FT /evidence="ECO:0000305"
FT CONFLICT 566
FT /note="G -> A (in Ref. 2; CAA55357)"
FT /evidence="ECO:0000305"
FT CONFLICT 578
FT /note="G -> A (in Ref. 2; CAA55357)"
FT /evidence="ECO:0000305"
FT CONFLICT 669
FT /note="G -> A (in Ref. 2; CAA55357)"
FT /evidence="ECO:0000305"
FT CONFLICT 708
FT /note="T -> I (in Ref. 2; CAA55357)"
FT /evidence="ECO:0000305"
FT CONFLICT 979
FT /note="T -> I (in Ref. 2; CAA55357)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1005 AA; 111007 MW; 1AED42C99693C574 CRC64;
MRGSGPRGAG RRRTQGRGGG GDTPRVPASL AGCYSAPLKG PLWTCLLLCA ALRTLLASPS
NEVNLLDSRT VLGDLGWIAF PKNGWEEIGE VDENYAPIHT YQVCKVMEQN QNNWLLTSWI
SNEGASRIFI ELKFTLRDCN SLPGGLGTCK ETFNMYYFES DDENGRNIKD NQYIKIDTIA
ADESFTELDL GDRVMKLNTE VRDVGPLSKK GFYLAFQDVG ACIALVSVRV YYKKCPSVVR
HLAVFPDTIT GADSSQLLEV SGSCVNHSVT DDPPKMHCSA EGEWLVPIGK CMCKAGYEEK
NGTCQVCRPG FFKASPHSQT CSKCPPHSYT HEEASTSCVC EKDYFRRESD PPTMACTRPP
SAPRNAISNV NETSVFLEWI PPADTGGGKD VSYYILCKKC NSHAGVCEEC GGHVRYLPQQ
IGLKNTSVMM ADPLAHTNYT FEIEAVNGVS DLSPGTRQYV SVNVTTNQAA PSPVTNVKKG
KIAKNSISLS WQEPDRPNGI ILEYEIKYFE KDQETSYTII KSKETTITAE GLKPASVYVF
QIRARTAAGY GVFSRRFEFE TTPVFGASND QSQIPIIGVS VTVGVILLAV MIGFLLSGSC
CECGCGRASS LCAVAHPSLI WRCGYSKAKQ DPEEEKMHFH NGHIKLPGVR TYIDPHTYED
PTQAVHEFGK EIEASCITIE RVIGAGEFGE VCSGRLKLPG KRELPVATKT LKVGYTEKQR
RDFLSEASIM GQFDHPNIIH LEGVVTKSKP VMIVTEYMEN GSLDTFLKKN DGQFTVIQLV
GMLRGIAAGM KYLSDMGYVH RDLAARNILI NSNLVCKVSD FGLSRVLEDD PEAAYTTRGG
KIPIRWTAPE AIAFRKFTSA SDVWSYGIVM WEVVSYGERP YWEMTNQDVI KAVEEGYRLP
SPMDCPAALY QLMLDCWQKD RNSRPKFDDI VNMLDKLIRN PSSLKTLVNA SSRVSTLLAE
HGSLGSGAYR SVGEWLEATK MGRYTEIFME NGYSSMDAVA QVTLE
