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Protein

Ephrin type-A receptor 5

Gene

Epha5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei546 – 5461ATPPROSITE-ProRule annotation
Active sitei639 – 6391Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi520 – 5289ATPPROSITE-ProRule annotation

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
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Biological processi

Neurogenesis

Keywords - Ligandi

ATP-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:99654. Epha5.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein Sequence analysis
  • Cell projectionaxon By similarity
  • Cell projectiondendrite By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini27 – 412386ExtracellularSequence analysisAdd
BLAST
Transmembranei413 – 43321HelicalSequence analysisAdd
BLAST
Topological domaini434 – 876443CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626By similarityAdd
BLAST
Chaini27 – 876850Ephrin type-A receptor 5PRO_0000016813Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi266 – 2661N-linked (GlcNAc...)Sequence analysis
Glycosylationi301 – 3011N-linked (GlcNAc...)Sequence analysis
Modified residuei489 – 4891Phosphotyrosine; by autocatalysisBy similarity
Modified residuei495 – 4951Phosphotyrosine; by autocatalysisBy similarity
Modified residuei672 – 6721Phosphotyrosine; by autocatalysisSequence analysis
Modified residuei821 – 8211Phosphotyrosine; by autocatalysisBy similarity

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.
PhosphoSiteiQ60629.

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).2 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.1 Publication

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 interactions.
STRINGi10090.ENSMUSP00000060646.

Structurei

3D structure databases

ProteinModelPortaliQ60629.
SMRiQ60629. Positions 59-397, 469-870.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini62 – 240179Eph LBDPROSITE-ProRule annotationAdd
BLAST
Domaini306 – 40095Fibronectin type-IIIPROSITE-ProRule annotationAdd
BLAST
Domaini514 – 775262Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini804 – 86865SAMPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi874 – 8763PDZ-bindingSequence analysis

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.PROSITE-ProRule annotation
Contains 1 Eph LBD (Eph ligand-binding) domain.PROSITE-ProRule annotation
Contains 1 fibronectin type-III domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.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

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 1 hit.
InterProiIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR001426. Tyr_kinase_rcpt_V_CS.
[Graphical view]
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 1 hit.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS01186. 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.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti532 – 5321R → C in AAA17038 (PubMed:8145300).Curated
Sequence conflicti697 – 6971S → A in AAA17038 (PubMed:8145300).Curated
Sequence conflicti855 – 8551Q → QK in AAA17038 (PubMed:8145300).Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ60629.
SMRiQ60629. Positions 59-397, 469-870.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ60629. 2 interactions.
STRINGi10090.ENSMUSP00000060646.

PTM databases

iPTMnetiQ60629.
PhosphoSiteiQ60629.

Proteomic databases

MaxQBiQ60629.
PaxDbiQ60629.
PRIDEiQ60629.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2044.
MGIiMGI:99654. Epha5.

Phylogenomic databases

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00760000118975.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiQ60629.
KOiK05106.
TreeFamiTF315363.

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.

Miscellaneous databases

ChiTaRSiEpha5. mouse.
PROiQ60629.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029245.
CleanExiMM_EPHA5.
ExpressionAtlasiQ60629. baseline and differential.
GenevisibleiQ60629. MM.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 1 hit.
InterProiIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR001426. Tyr_kinase_rcpt_V_CS.
[Graphical view]
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM00060. FN3. 1 hit.
SM00454. SAM. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS01186. 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.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEPHA5_MOUSE
AccessioniPrimary (citable) accession number: Q60629
Secondary accession number(s): E9QPV2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 19, 2011
Last modified: September 7, 2016
This is version 161 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.