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Protein

Ephrin type-A receptor 5

Gene

Epha5

Organism
Rattus norvegicus (Rat)
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 (By similarity).By similarity3 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 sitei709 – 7091ATPPROSITE-ProRule annotation
Active sitei802 – 8021Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi683 – 6919ATPPROSITE-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
  • dendritic spine morphogenesis Source: UniProtKB
  • 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. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 5 (EC:2.7.10.1)
Alternative name(s):
EPH homology kinase 1
Short name:
EHK-1
Gene namesi
Name:Epha5
Synonyms:Ehk-1, Ekh1, Rek7
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620831. Epha5.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini27 – 575549ExtracellularSequence analysisAdd
BLAST
Transmembranei576 – 59621HelicalSequence analysisAdd
BLAST
Topological domaini597 – 1005409CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Chemistry

GuidetoPHARMACOLOGYi1825.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626By similarityAdd
BLAST
Chaini27 – 1005979Ephrin type-A receptor 5PRO_0000016814Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi266 – 2661N-linked (GlcNAc...)Sequence analysis
Glycosylationi301 – 3011N-linked (GlcNAc...)Sequence analysis
Glycosylationi371 – 3711N-linked (GlcNAc...)Sequence analysis
Glycosylationi425 – 4251N-linked (GlcNAc...)Sequence analysis
Glycosylationi438 – 4381N-linked (GlcNAc...)Sequence analysis
Glycosylationi463 – 4631N-linked (GlcNAc...)Sequence analysisVSP_003000
Modified residuei652 – 6521Phosphotyrosine; by autocatalysisBy similarity
Modified residuei658 – 6581Phosphotyrosine; by autocatalysisBy similarity
Modified residuei835 – 8351Phosphotyrosine; by autocatalysisSequence analysis
Modified residuei984 – 9841Phosphotyrosine; 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 (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP54757.
PRIDEiP54757.

PTM databases

iPTMnetiP54757.
PhosphoSiteiP54757.
SwissPalmiP54757.

Expressioni

Tissue specificityi

Almost exclusively expressed in the nervous system. Predominantly expressed in neurons.1 Publication

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000002793.

Structurei

3D structure databases

ProteinModelPortaliP54757.
SMRiP54757. Positions 62-237, 664-942.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini62 – 240179Eph LBDPROSITE-ProRule annotationAdd
BLAST
Domaini359 – 469111Fibronectin type-III 1PROSITE-ProRule annotationAdd
BLAST
Domaini470 – 56495Fibronectin type-III 2PROSITE-ProRule annotationAdd
BLAST
Domaini677 – 938262Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini967 – 100539SAMPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi222 – 356135Cys-richAdd
BLAST

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 2 fibronectin type-III domains.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SAM (sterile alpha motif) domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiP54757.
KOiK05106.
PhylomeDBiP54757.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
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.
[Graphical view]
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM01411. Ephrin_rec_like. 1 hit.
SM00060. FN3. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS01186. EGF_2. 1 hit.
PS51550. EPH_LBD. 1 hit.
PS50853. FN3. 2 hits.
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]

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P54757-1) [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
MRGSGPRGAG RRRTQGRGGG GDTPRVPASL AGCYSAPLKG PLWTCLLLCA
60 70 80 90 100
ALRTLLASPS NEVNLLDSRT VLGDLGWIAF PKNGWEEIGE VDENYAPIHT
110 120 130 140 150
YQVCKVMEQN QNNWLLTSWI SNEGASRIFI ELKFTLRDCN SLPGGLGTCK
160 170 180 190 200
ETFNMYYFES DDENGRNIKD NQYIKIDTIA ADESFTELDL GDRVMKLNTE
210 220 230 240 250
VRDVGPLSKK GFYLAFQDVG ACIALVSVRV YYKKCPSVVR HLAVFPDTIT
260 270 280 290 300
GADSSQLLEV SGSCVNHSVT DDPPKMHCSA EGEWLVPIGK CMCKAGYEEK
310 320 330 340 350
NGTCQVCRPG FFKASPHSQT CSKCPPHSYT HEEASTSCVC EKDYFRRESD
360 370 380 390 400
PPTMACTRPP SAPRNAISNV NETSVFLEWI PPADTGGGKD VSYYILCKKC
410 420 430 440 450
NSHAGVCEEC GGHVRYLPQQ IGLKNTSVMM ADPLAHTNYT FEIEAVNGVS
460 470 480 490 500
DLSPGTRQYV SVNVTTNQAA PSPVTNVKKG KIAKNSISLS WQEPDRPNGI
510 520 530 540 550
ILEYEIKYFE KDQETSYTII KSKETTITAE GLKPASVYVF QIRARTAAGY
560 570 580 590 600
GVFSRRFEFE TTPVFGASND QSQIPIIGVS VTVGVILLAV MIGFLLSGSC
610 620 630 640 650
CECGCGRASS LCAVAHPSLI WRCGYSKAKQ DPEEEKMHFH NGHIKLPGVR
660 670 680 690 700
TYIDPHTYED PTQAVHEFGK EIEASCITIE RVIGAGEFGE VCSGRLKLPG
710 720 730 740 750
KRELPVATKT LKVGYTEKQR RDFLSEASIM GQFDHPNIIH LEGVVTKSKP
760 770 780 790 800
VMIVTEYMEN GSLDTFLKKN DGQFTVIQLV GMLRGIAAGM KYLSDMGYVH
810 820 830 840 850
RDLAARNILI NSNLVCKVSD FGLSRVLEDD PEAAYTTRGG KIPIRWTAPE
860 870 880 890 900
AIAFRKFTSA SDVWSYGIVM WEVVSYGERP YWEMTNQDVI KAVEEGYRLP
910 920 930 940 950
SPMDCPAALY QLMLDCWQKD RNSRPKFDDI VNMLDKLIRN PSSLKTLVNA
960 970 980 990 1000
SSRVSTLLAE HGSLGSGAYR SVGEWLEATK MGRYTEIFME NGYSSMDAVA

QVTLE
Length:1,005
Mass (Da):111,007
Last modified:October 1, 1996 - v1
Checksum:i1AED42C99693C574
GO
Isoform 2 (identifier: P54757-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     306-357: VCRPGFFKASPHSQTCSKCPPHSYTHEEASTSCVCEKDYFRRESDPPTMACT → G

Show »
Length:954
Mass (Da):105,241
Checksum:iA576627951A20FE0
GO
Isoform 3 (identifier: P54757-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     358-470: RPPSAPRNAI...SVNVTTNQAA → T

Show »
Length:893
Mass (Da):98,956
Checksum:iCC3FC19A3DAD4F67
GO
Isoform 4 (identifier: P54757-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     358-470: RPPSAPRNAI...SVNVTTNQAA → T
     597-621: SGSCCECGCGRASSLCAVAHPSLIW → R

Show »
Length:869
Mass (Da):96,632
Checksum:i02B991C14388F987
GO
Isoform 5 (identifier: P54757-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     306-357: VCRPGFFKASPHSQTCSKCPPHSYTHEEASTSCVCEKDYFRRESDPPTMACT → G
     358-470: RPPSAPRNAI...SVNVTTNQAA → T
     597-621: SGSCCECGCGRASSLCAVAHPSLIW → R

Show »
Length:818
Mass (Da):90,866
Checksum:i78A72B1189C07F64
GO

Sequence cautioni

Isoform 3 : The sequence CAA55357 differs from that shown. Reason: Frameshift at several positions. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti170 – 1701D → E in CAA55357 (PubMed:7898646).Curated
Sequence conflicti566 – 5661G → A in CAA55357 (PubMed:7898646).Curated
Sequence conflicti578 – 5781G → A in CAA55357 (PubMed:7898646).Curated
Sequence conflicti669 – 6691G → A in CAA55357 (PubMed:7898646).Curated
Sequence conflicti708 – 7081T → I in CAA55357 (PubMed:7898646).Curated
Sequence conflicti979 – 9791T → I in CAA55357 (PubMed:7898646).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei306 – 35752VCRPG…TMACT → G in isoform 2 and isoform 5. 1 PublicationVSP_003001Add
BLAST
Alternative sequencei358 – 470113RPPSA…TNQAA → T in isoform 3, isoform 4 and isoform 5. 2 PublicationsVSP_003002Add
BLAST
Alternative sequencei597 – 62125SGSCC…PSLIW → R in isoform 4 and isoform 5. 1 PublicationVSP_003003Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X78689 mRNA. Translation: CAA55357.1. Frameshift.
PIRiPT0186.
S47489.
S49015.
S51603.
S51604.
RefSeqiNP_077343.1. NM_024367.1.
UniGeneiRn.24569.

Genome annotation databases

GeneIDi79208.
KEGGirno:79208.
UCSCiRGD:620831. rat. [P54757-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X78689 mRNA. Translation: CAA55357.1. Frameshift.
PIRiPT0186.
S47489.
S49015.
S51603.
S51604.
RefSeqiNP_077343.1. NM_024367.1.
UniGeneiRn.24569.

3D structure databases

ProteinModelPortaliP54757.
SMRiP54757. Positions 62-237, 664-942.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000002793.

Chemistry

GuidetoPHARMACOLOGYi1825.

PTM databases

iPTMnetiP54757.
PhosphoSiteiP54757.
SwissPalmiP54757.

Proteomic databases

PaxDbiP54757.
PRIDEiP54757.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi79208.
KEGGirno:79208.
UCSCiRGD:620831. rat. [P54757-1]

Organism-specific databases

CTDi2044.
RGDi620831. Epha5.

Phylogenomic databases

eggNOGiKOG0196. Eukaryota.
COG0515. LUCA.
HOGENOMiHOG000233856.
HOVERGENiHBG062180.
InParanoidiP54757.
KOiK05106.
PhylomeDBiP54757.

Enzyme and pathway databases

BRENDAi2.7.10.1. 5301.

Miscellaneous databases

PROiP54757.

Family and domain databases

Gene3Di1.10.150.50. 1 hit.
2.60.120.260. 1 hit.
2.60.40.10. 2 hits.
InterProiIPR027936. Eph_TM.
IPR001090. Ephrin_rcpt_lig-bd_dom.
IPR003961. FN3_dom.
IPR008979. Galactose-bd-like.
IPR009030. Growth_fac_rcpt_.
IPR013783. Ig-like_fold.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR001660. SAM.
IPR013761. SAM/pointed.
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.
[Graphical view]
PfamiPF14575. EphA2_TM. 1 hit.
PF01404. Ephrin_lbd. 1 hit.
PF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
PF00536. SAM_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000666. TyrPK_ephrin_receptor. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00615. EPH_lbd. 1 hit.
SM01411. Ephrin_rec_like. 1 hit.
SM00060. FN3. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF47769. SSF47769. 1 hit.
SSF49265. SSF49265. 1 hit.
SSF49785. SSF49785. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF57184. SSF57184. 2 hits.
PROSITEiPS01186. EGF_2. 1 hit.
PS51550. EPH_LBD. 1 hit.
PS50853. FN3. 2 hits.
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_RAT
AccessioniPrimary (citable) accession number: P54757
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 6, 2016
This is version 154 of the entry and version 1 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. 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.