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Protein

Ephrin type-A receptor 5

Gene

Epha5

Organism
Mus musculus (Mouse)
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 most probably constitutes the cognate/functional ligand for EPHA5. Functions as an axon guidance molecule during development and may be involved in the development of the retinotectal, entorhino-hippocampal and hippocamposeptal pathways. Together with EFNA5 plays also a role in synaptic plasticity in adult brain through regulation of synaptogenesis. In addition to its function in the nervous system, the interaction of EPHA5 with EFNA5 mediates communication between pancreatic islet cells to regulate glucose-stimulated insulin secretion.2 Publications

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei546ATPPROSITE-ProRule annotation1
Active sitei639Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi520 – 528ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • ephrin receptor activity Source: UniProtKB
  • GPI-linked ephrin receptor activity Source: UniProtKB

GO - Biological processi

  • axon guidance Source: UniProtKB
  • cAMP-mediated signaling Source: UniProtKB
  • cellular response to follicle-stimulating hormone stimulus Source: MGI
  • cellular response to forskolin Source: MGI
  • ephrin receptor signaling pathway Source: UniProtKB
  • hippocampus development Source: UniProtKB
  • negative regulation of cell adhesion Source: MGI
  • positive regulation of CREB transcription factor activity Source: UniProtKB
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of GTPase activity Source: UniProtKB
  • regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
Biological processNeurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 3474
ReactomeiR-MMU-2682334 EPH-Ephrin signaling
R-MMU-3928663 EPHA-mediated growth cone collapse
R-MMU-3928665 EPH-ephrin mediated repulsion of cells

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 5 (EC:2.7.10.1)
Alternative name(s):
Brain-specific kinase
CEK-7
EPH homology kinase 1
Short name:
EHK-1
Gene namesi
Name:Epha5
Synonyms:Bsk, Ehk1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:99654 Epha5

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 domaini27 – 412ExtracellularSequence analysisAdd BLAST386
Transmembranei413 – 433HelicalSequence analysisAdd BLAST21
Topological domaini434 – 876CytoplasmicSequence analysisAdd BLAST443

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26By similarityAdd BLAST26
ChainiPRO_000001681327 – 876Ephrin type-A receptor 5Add BLAST850

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi266N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi301N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei489Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei495Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei672Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei821Phosphotyrosine; by autocatalysisBy similarity1

Post-translational modificationi

Phosphorylated. Phosphorylation is stimulated by the ligand EFNA5. Dephosphorylation upon stimulation by glucose, inhibits EPHA5 forward signaling and results in insulin secretion.2 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ60629
PaxDbiQ60629
PRIDEiQ60629

PTM databases

iPTMnetiQ60629
PhosphoSitePlusiQ60629
SwissPalmiQ60629

Expressioni

Tissue specificityi

Specifically expressed in the brain. Highly expressed in hippocampus, tenia tecta, indusium griseum and piriform cortex. The highest level of expression is found in the CA3 region of the hippocampus and the pyramidal cell layer of the piriform cortex. In addition, elevated levels of expression are also found in amygdala, medial septum, nucleus of the diagonal band, and in olfactory bulb. Expressed in pancreatic islet cells (at protein level). Expressed in myogenic progenitor cells (PubMed:27446912).3 Publications

Developmental stagei

Within the developing nervous system, the expression is very dynamic. At E16.5 expressed predominantly in the primordial cortex of the telencephalon. Besides the midbrain it is also expressed in the hypothalamus, and the neurohypophysis. Non neuronal expression domains include the ectoderm of the branchial arches, the ectoderm and mesenchyme surrounding the dorsal root ganglia, the intervertebral disks, maxillary and mandibulary mesenchymal elements as well as the nasal mesenchyme and ectoderm. In myogenic progenitor cells, expressed at least as early as E11.5 until adulthood (PubMed:27446912).2 Publications

Gene expression databases

BgeeiENSMUSG00000029245
CleanExiMM_EPHA5
ExpressionAtlasiQ60629 baseline and differential
GenevisibleiQ60629 MM

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
RetP35546-25EBI-1267609,EBI-5548911

Protein-protein interaction databases

IntActiQ60629, 2 interactors
STRINGi10090.ENSMUSP00000060646

Structurei

3D structure databases

ProteinModelPortaliQ60629
SMRiQ60629
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini62 – 240Eph LBDPROSITE-ProRule annotationAdd BLAST179
Domaini306 – 400Fibronectin type-IIIPROSITE-ProRule annotationAdd BLAST95
Domaini514 – 775Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini804 – 868SAMPROSITE-ProRule annotationAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi874 – 876PDZ-bindingSequence analysis3

Sequence similaritiesi

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0196 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00760000118975
HOGENOMiHOG000233856
HOVERGENiHBG062180
InParanoidiQ60629
KOiK05106
TreeFamiTF315363

Family and domain databases

CDDicd10483 EphR_LBD_A5, 1 hit
cd00063 FN3, 1 hit
Gene3Di2.60.120.260, 1 hit
2.60.40.10, 1 hit
InterProiView protein in InterPro
IPR027936 Eph_TM
IPR034277 EphA5_rcpt_lig-bd
IPR001090 Ephrin_rcpt_lig-bd_dom
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR008979 Galactose-bd-like_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
IPR008266 Tyr_kinase_AS
IPR020635 Tyr_kinase_cat_dom
IPR001426 Tyr_kinase_rcpt_V_CS
PfamiView protein in Pfam
PF14575 EphA2_TM, 1 hit
PF01404 Ephrin_lbd, 1 hit
PF00041 fn3, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF00536 SAM_1, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00615 EPH_lbd, 1 hit
SM00060 FN3, 1 hit
SM00454 SAM, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF47769 SSF47769, 1 hit
SSF49265 SSF49265, 1 hit
SSF49785 SSF49785, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01186 EGF_2, 1 hit
PS51550 EPH_LBD, 1 hit
PS50853 FN3, 1 hit
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

Sequencei

Sequence statusi: Complete.

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

Q60629-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRGSGPRGAG HRRTQGRGGG DDTPRVPASL AGCYSAPLKG PLWTCLLLCA
60 70 80 90 100
ALRTLLASPS NEVNLLDSRT VMGDLGWIAF PKNGWEEIGE VDENYAPIHT
110 120 130 140 150
YQVCKVMEQN QNNWLLTSWI SNEGASRIFI ELKFTLRDCN SLPGGLGTCK
160 170 180 190 200
ETFNMYYFES DDENGRSIKE NQYIKIDTIA ADESFTELDL GDRVMKLNTE
210 220 230 240 250
VRDVGPLSKK GFYLAFQDVG ACIALVSVRV YYKKCPSVVR HLAIFPDTIT
260 270 280 290 300
GADSSQLLEV SGSCVNHSVT DDPPKMHCSA EGEWLVPIGK CMCKAGYEEK
310 320 330 340 350
NGTCQAPSPV TNVKKGKIAK NSISLSWQEP DRPNGIILEY EIKYFEKDQE
360 370 380 390 400
TSYTIIKSKE TSITAEGLKP ASVYVFQIRA RTAAGYGVFS RRFEFETTPV
410 420 430 440 450
SVAASNDQSQ IPIIAVSVTV GVILLAVMIG FLLSGSCCDC GCGRASSLCA
460 470 480 490 500
VAHPSLIWRC GYSKAKQDPE EEKMHFHNGH IKLPGVRTYI DPHTYEDPNQ
510 520 530 540 550
AVHEFAKEIE ASCITIERVI GAGEFGEVCS GRLKLPGKRE LPVAIKTLKV
560 570 580 590 600
GYTEKQRRDF LGEASIMGQF DHPNIIHLEG VVTKSKPVMI VTEYMENGSL
610 620 630 640 650
DTFLKKNDGQ FTVIQLVGML RGIAAGMKYL SDMGYVHRDL AARNILINSN
660 670 680 690 700
LVCKVSDFGL SRVLEDDPEA AYTTRGGKIP IRWTAPEAIA FRKFTSSSDV
710 720 730 740 750
WSYGIVMWEV VSYGERPYWE MTNQDVIKAV EEGYRLPSPM DCPAALYQLM
760 770 780 790 800
LDCWQKDRNS RPKFDEIVNM LDKLIRNPSS LKTLVNASSR VSTLLAEHGS
810 820 830 840 850
LGSGAYRSVG EWLEAIKMGR YTEIFMENGY SSMDAVAQVT LEDLRRLGVT
860 870
LVGHQKKIMS SLQEMKVQMV NGMVPV
Length:876
Mass (Da):97,056
Last modified:October 19, 2011 - v2
Checksum:iD6539F74DCB6B763
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti532R → C in AAA17038 (PubMed:8145300).Curated1
Sequence conflicti697S → A in AAA17038 (PubMed:8145300).Curated1
Sequence conflicti855Q → QK in AAA17038 (PubMed:8145300).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U07357 mRNA Translation: AAA17038.1
AC101956 Genomic DNA No translation available.
AC114638 Genomic DNA No translation available.
AC129220 Genomic DNA No translation available.
AC132597 Genomic DNA No translation available.
CCDSiCCDS19376.1
PIRiI48967
RefSeqiNP_031963.2, NM_007937.3
UniGeneiMm.137991
Mm.438006

Genome annotation databases

EnsembliENSMUST00000053733; ENSMUSP00000060646; ENSMUSG00000029245
GeneIDi13839
KEGGimmu:13839
UCSCiuc008xwv.3 mouse

Similar proteinsi

Entry informationi

Entry nameiEPHA5_MOUSE
AccessioniPrimary (citable) accession number: Q60629
Secondary accession number(s): E9QPV2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 19, 2011
Last modified: May 23, 2018
This is version 171 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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