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Protein

Ephrin type-A receptor 7

Gene

Epha7

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A 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. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 AND MAPK3 which are phosphorylated upon activation of EPHA7.1 Publication

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei665ATPPROSITE-ProRule annotation1
Active sitei758Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi639 – 647ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • axon guidance receptor activity Source: UniProtKB
  • chemorepellent activity Source: UniProtKB
  • ephrin receptor activity Source: RGD
  • ephrin receptor binding Source: RGD
  • GPI-linked ephrin receptor activity Source: UniProtKB
  • protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Kinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processApoptosis, Neurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 5301
ReactomeiR-RNO-2682334 EPH-Ephrin signaling
R-RNO-3928663 EPHA-mediated growth cone collapse
R-RNO-3928665 EPH-ephrin mediated repulsion of cells

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 7 (EC:2.7.10.1)
Alternative name(s):
EPH homology kinase 3
Short name:
EHK-3
Gene namesi
Name:Epha7
Synonyms:Ehk-3, Ehk3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi70957 Epha7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 555ExtracellularSequence analysisAdd BLAST528
Transmembranei556 – 576HelicalSequence analysisAdd BLAST21
Topological domaini577 – 998CytoplasmicSequence analysisAdd BLAST422

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000001682028 – 998Ephrin type-A receptor 7Add BLAST971

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi343N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi410N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei608Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei614Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei791Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei940Phosphotyrosine; by autocatalysisSequence analysis1

Post-translational modificationi

Phosphorylated.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP54759
PRIDEiP54759

PTM databases

iPTMnetiP54759
PhosphoSitePlusiP54759

Expressioni

Tissue specificityi

Restricted to the nervous system.

Gene expression databases

BgeeiENSRNOG00000007030
GenevisibleiP54759 RN

Interactioni

Subunit structurei

Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses (By similarity). Interacts (via PDZ-binding motif) with GRIP1 and PICK1 (via PDZ domain) (By similarity).By similarity

GO - Molecular functioni

  • chemorepellent activity Source: UniProtKB
  • ephrin receptor binding Source: RGD

Protein-protein interaction databases

IntActiP54759, 3 interactors
STRINGi10116.ENSRNOP00000009899

Structurei

3D structure databases

ProteinModelPortaliP54759
SMRiP54759
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 210Eph LBDPROSITE-ProRule annotationAdd BLAST179
Domaini331 – 441Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST111
Domaini442 – 537Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST96
Domaini633 – 894Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini923 – 987SAMPROSITE-ProRule annotationAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi996 – 998PDZ-bindingSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi192 – 328Cys-richAdd BLAST137

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118975
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiP54759
KOiK05108
OMAiTRHPSWI
OrthoDBiEOG091G00W0
PhylomeDBiP54759
TreeFamiTF315608

Family and domain databases

CDDicd10485 EphR_LBD_A7, 1 hit
cd00063 FN3, 2 hits
Gene3Di2.60.120.260, 1 hit
2.60.40.10, 2 hits
InterProiView protein in InterPro
IPR027936 Eph_TM
IPR034283 EphA7_rcpt_lig-bd
IPR001090 Ephrin_rcpt_lig-bd_dom
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR008979 Galactose-bd-like_sf
IPR009030 Growth_fac_rcpt_cys_sf
IPR013783 Ig-like_fold
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR001660 SAM
IPR013761 SAM/pointed_sf
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
IPR011641 Tyr-kin_ephrin_A/B_rcpt-like
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR016257 Tyr_kinase_ephrin_rcpt
IPR001426 Tyr_kinase_rcpt_V_CS
PfamiView protein in Pfam
PF14575 EphA2_TM, 1 hit
PF01404 Ephrin_lbd, 1 hit
PF00041 fn3, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PF00536 SAM_1, 1 hit
PIRSFiPIRSF000666 TyrPK_ephrin_receptor, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00615 EPH_lbd, 1 hit
SM01411 Ephrin_rec_like, 1 hit
SM00060 FN3, 2 hits
SM00454 SAM, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF49265 SSF49265, 1 hit
SSF49785 SSF49785, 1 hit
SSF56112 SSF56112, 1 hit
SSF57184 SSF57184, 1 hit
PROSITEiView protein in PROSITE
PS01186 EGF_2, 1 hit
PS51550 EPH_LBD, 1 hit
PS50853 FN3, 2 hits
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00109 PROTEIN_KINASE_TYR, 1 hit
PS00790 RECEPTOR_TYR_KIN_V_1, 1 hit
PS00791 RECEPTOR_TYR_KIN_V_2, 1 hit
PS50105 SAM_DOMAIN, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P54759-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVVQTRYPSW IILCYIWLLG FAHTGEAQAA KEVLLLDSKA QQTELEWISS
60 70 80 90 100
PPSGWEEISG LDENYTPIRT YQVCQVMEPN QNNWLRTNWI SKGNAQRIFV
110 120 130 140 150
ELKFTLRDCN SLPGVLGTCK ETFNLYYYET DYDTGRNIRE NLYVKIDTIA
160 170 180 190 200
ADESFTQGDL GERKMKLNTE VREIGPLSKK GFYLAFQDVG ACIALVSVKV
210 220 230 240 250
YYKKCWSIIE NLAVFPDTVT GSEFSSLVEV RGTCVSSAEE EAENSPRMHC
260 270 280 290 300
SAEGEWLVPI GKCICKAGYQ QKGDTCEPCG RRFYKSSSQD LQCSRCPTHS
310 320 330 340 350
FSDREGSSRC ECEDGYYRAP SDPPYVACTR PPSAPQNLIF NINQTTVSLE
360 370 380 390 400
WSPPADNGGR NDVTYRILCK RCSWEQGECV PCGSNIGYMP QQTGLEDNYV
410 420 430 440 450
TVMDLLAHAN YTFEVEAVNG VSDLSRSQRL FAAVSITTGQ AAPSQVSGVM
460 470 480 490 500
KERVLQRSVE LSWQEPEHPN GVITEYEIKY YEKDQRERTY STLKTKSTSA
510 520 530 540 550
SINNLKPGTV YVFQIRAFTA AGYGNYSPRL DVATLEEASG KMFEATAVSS
560 570 580 590 600
EQNPVIIIAV VAVAGTIILV FMVFGFIIGR RHCGYSKADQ EGDEELYFHF
610 620 630 640 650
KFPGTKTYID PETYEDPNRA VHQFAKELDA SCIKIERVIG AGEFGEVCSG
660 670 680 690 700
RLKLPGKRDV AVAIKTLKVG YTEKQRRDFL CEASIMGQFD HPNVVHLEGV
710 720 730 740 750
VTRGKPVMIV IEFMENGALD AFLRKHDGQF TVIQLVGMLR GIAAGMRYLA
760 770 780 790 800
DMGYVHRDLA ARNILVNSNL VCKVSDFGLS RVIEDDPEAV YTTTGGKIPV
810 820 830 840 850
RWTAPEAIQY RKFTSASDVW SYGIVMWEVM SYGERPYWDM SNQDVIKAIE
860 870 880 890 900
EGYRLPAPMD CPAGLHQLML DCWQKERAER PKFEQIVGIL DKMIRNPSSL
910 920 930 940 950
KTPLGTCSRP ISPLLDQSTP DFTAFCSVGE WLQAIKMERY KDNFTAAGYN
960 970 980 990
SLESVARMTI DDVMSLGITL VGHQKKIMSS IQTMRAQMLH LHGTGIQV
Note: More widely expressed in the embryo.
Length:998
Mass (Da):111,953
Last modified:October 1, 1996 - v1
Checksum:iA7A82A698924876C
GO
Isoform Short (identifier: P54759-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     600-610: FKFPGTKTYID → SLVTNEHLSVL

Note: Lacks the kinase domain.
Show »
Length:998
Mass (Da):111,848
Checksum:iB87536EA0D7CB919
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003012600 – 610FKFPGTKTYID → SLVTNEHLSVL in isoform Short. 1 PublicationAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U21954 mRNA Translation: AAA86830.1
U21955 mRNA Translation: AAA86831.1
RefSeqiNP_599158.1, NM_134331.1 [P54759-1]
XP_006238026.1, XM_006237964.3
UniGeneiRn.10181

Genome annotation databases

EnsembliENSRNOT00000009899; ENSRNOP00000009899; ENSRNOG00000007030 [P54759-1]
GeneIDi171287
KEGGirno:171287
UCSCiRGD:70957 rat [P54759-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiEPHA7_RAT
AccessioniPrimary (citable) accession number: P54759
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: May 23, 2018
This is version 169 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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