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UniProtKB - P54756 (EPHA5_HUMAN)

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Protein

Ephrin type-A receptor 5

Gene

EPHA5

Organism
Homo sapiens (Human)
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 (By similarity).By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei707ATPPROSITE-ProRule annotation1
Active sitei800Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi681 – 689ATPPROSITE-ProRule annotation9

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

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

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
ReactomeiR-HSA-2682334 EPH-Ephrin signaling
R-HSA-3928663 EPHA-mediated growth cone collapse
R-HSA-3928665 EPH-ephrin mediated repulsion of cells
SignaLinkiP54756
SIGNORiP54756

Names & Taxonomyi

Protein namesi
Recommended name:
Ephrin type-A receptor 5 (EC:2.7.10.1)
Alternative name(s):
Brain-specific kinase
EPH homology kinase 1
Short name:
EHK-1
EPH-like kinase 7
Short name:
EK7
Short name:
hEK7
Gene namesi
Name:EPHA5
Synonyms:BSK, EHK1, HEK7, TYRO4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000145242.13
HGNCiHGNC:3389 EPHA5
MIMi600004 gene
neXtProtiNX_P54756

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 domaini25 – 573ExtracellularSequence analysisAdd BLAST549
Transmembranei574 – 594HelicalSequence analysisAdd BLAST21
Topological domaini595 – 1037CytoplasmicSequence analysisAdd BLAST443

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2044
OpenTargetsiENSG00000145242
PharmGKBiPA27821

Chemistry databases

ChEMBLiCHEMBL3987
GuidetoPHARMACOLOGYi1825

Polymorphism and mutation databases

BioMutaiEPHA5
DMDMi259016353

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000001681225 – 1037Ephrin type-A receptor 5Add BLAST1013

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi264N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi299N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi369N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi423N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi436N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi461N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei650Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei656Phosphotyrosine; by autocatalysisBy similarity1
Modified residuei833Phosphotyrosine; by autocatalysisSequence analysis1
Modified residuei982Phosphotyrosine; 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 (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP54756
MaxQBiP54756
PaxDbiP54756
PeptideAtlasiP54756
PRIDEiP54756
ProteomicsDBi56712
56713 [P54756-2]
56714 [P54756-3]
TopDownProteomicsiP54756-2 [P54756-2]

PTM databases

iPTMnetiP54756
PhosphoSitePlusiP54756

Expressioni

Tissue specificityi

Almost exclusively expressed in the nervous system in cortical neurons, cerebellar Purkinje cells and pyramidal neurons within the cortex and hippocampus. Display an increasing gradient of expression from the forebrain to hindbrain and spinal cord.2 Publications

Gene expression databases

BgeeiENSG00000145242
CleanExiHS_EPHA5
ExpressionAtlasiP54756 baseline and differential
GenevisibleiP54756 HS

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

BioGridi108358, 7 interactors
IntActiP54756, 2 interactors
MINTiP54756
STRINGi9606.ENSP00000273854

Chemistry databases

BindingDBiP54756

Structurei

Secondary structure

11037
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi61 – 65Combined sources5
Turni66 – 68Combined sources3
Beta strandi76 – 89Combined sources14
Beta strandi95 – 101Combined sources7
Beta strandi105 – 107Combined sources3
Beta strandi111 – 114Combined sources4
Beta strandi126 – 135Combined sources10
Helixi137 – 139Combined sources3
Beta strandi148 – 157Combined sources10
Helixi166 – 168Combined sources3
Beta strandi172 – 178Combined sources7
Beta strandi188 – 192Combined sources5
Beta strandi196 – 202Combined sources7
Beta strandi207 – 219Combined sources13
Beta strandi221 – 230Combined sources10
Helixi663 – 665Combined sources3
Helixi672 – 674Combined sources3
Beta strandi675 – 683Combined sources9
Beta strandi685 – 694Combined sources10
Beta strandi702 – 708Combined sources7
Helixi715 – 728Combined sources14
Beta strandi739 – 743Combined sources5
Beta strandi745 – 748Combined sources4
Beta strandi750 – 754Combined sources5
Helixi761 – 766Combined sources6
Turni767 – 770Combined sources4
Helixi774 – 793Combined sources20
Helixi803 – 805Combined sources3
Beta strandi806 – 808Combined sources3
Beta strandi814 – 816Combined sources3
Helixi842 – 844Combined sources3
Helixi847 – 852Combined sources6
Helixi857 – 873Combined sources17
Turni878 – 881Combined sources4
Helixi884 – 893Combined sources10
Helixi905 – 914Combined sources10
Helixi919 – 921Combined sources3
Helixi925 – 936Combined sources12

3D structure databases

ProteinModelPortaliP54756
SMRiP54756
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54756

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini60 – 238Eph LBDPROSITE-ProRule annotationAdd BLAST179
Domaini357 – 467Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST111
Domaini468 – 562Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST95
Domaini675 – 936Protein kinasePROSITE-ProRule annotationAdd BLAST262
Domaini965 – 1029SAMPROSITE-ProRule annotationAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1035 – 1037PDZ-bindingSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi220 – 354Cys-richAdd BLAST135

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
HOVERGENiHBG062180
InParanoidiP54756
KOiK05106
PhylomeDBiP54756
TreeFamiTF315608

Family and domain databases

CDDicd10483 EphR_LBD_A5, 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
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
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
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 (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P54756-1) [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 RRRPPSGGGD TPITPASLAG CYSAPRRAPL WTCLLLCAAL 
        60         70         80         90        100
RTLLASPSNE VNLLDSRTVM GDLGWIAFPK NGWEEIGEVD ENYAPIHTYQ 
       110        120        130        140        150
VCKVMEQNQN NWLLTSWISN EGASRIFIEL KFTLRDCNSL PGGLGTCKET 
       160        170        180        190        200
FNMYYFESDD QNGRNIKENQ YIKIDTIAAD ESFTELDLGD RVMKLNTEVR 
       210        220        230        240        250
DVGPLSKKGF YLAFQDVGAC IALVSVRVYY KKCPSVVRHL AVFPDTITGA 
       260        270        280        290        300
DSSQLLEVSG SCVNHSVTDE PPKMHCSAEG EWLVPIGKCM CKAGYEEKNG 
       310        320        330        340        350
TCQVCRPGFF KASPHIQSCG KCPPHSYTHE EASTSCVCEK DYFRRESDPP 
       360        370        380        390        400
TMACTRPPSA PRNAISNVNE TSVFLEWIPP ADTGGRKDVS YYIACKKCNS 
       410        420        430        440        450
HAGVCEECGG HVRYLPRQSG LKNTSVMMVD LLAHTNYTFE IEAVNGVSDL 
       460        470        480        490        500
SPGARQYVSV NVTTNQAAPS PVTNVKKGKI AKNSISLSWQ EPDRPNGIIL 
       510        520        530        540        550
EYEIKYFEKD QETSYTIIKS KETTITAEGL KPASVYVFQI RARTAAGYGV 
       560        570        580        590        600
FSRRFEFETT PVFAASSDQS QIPVIAVSVT VGVILLAVVI GVLLSGSCCE 
       610        620        630        640        650
CGCGRASSLC AVAHPSLIWR CGYSKAKQDP EEEKMHFHNG HIKLPGVRTY 
       660        670        680        690        700
IDPHTYEDPN QAVHEFAKEI EASCITIERV IGAGEFGEVC SGRLKLPGKR 
       710        720        730        740        750
ELPVAIKTLK VGYTEKQRRD FLGEASIMGQ FDHPNIIHLE GVVTKSKPVM 
       760        770        780        790        800
IVTEYMENGS LDTFLKKNDG QFTVIQLVGM LRGISAGMKY LSDMGYVHRD 
       810        820        830        840        850
LAARNILINS NLVCKVSDFG LSRVLEDDPE AAYTTRGGKI PIRWTAPEAI 
       860        870        880        890        900
AFRKFTSASD VWSYGIVMWE VVSYGERPYW EMTNQDVIKA VEEGYRLPSP 
       910        920        930        940        950
MDCPAALYQL MLDCWQKERN SRPKFDEIVN MLDKLIRNPS SLKTLVNASC 
       960        970        980        990       1000
RVSNLLAEHS PLGSGAYRSV GEWLEAIKMG RYTEIFMENG YSSMDAVAQV 
      1010       1020       1030 
TLEDLRRLGV TLVGHQKKIM NSLQEMKVQL VNGMVPL
Length:1,037
Mass (Da):114,803
Last modified:September 22, 2009 - v3
Checksum:i578C2F4D950DE419
GO
Isoform 2 (identifier: P54756-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     597-619: SCCECGCGRASSLCAVAHPSLIW → R

Show »
Length:1,015
Mass (Da):112,624
Checksum:i0C0121184BCE631E
GO
Isoform 3 (identifier: P54756-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: Missing.
     563-563: F → SV

Show »
Length:969
Mass (Da):107,699
Checksum:i3038A240682F6E84
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti11R → H in CAA64700 (PubMed:9191074).Curated1
Sequence conflicti87G → D in CAD97914 (PubMed:17974005).Curated1
Sequence conflicti506Y → H in CAA64700 (PubMed:9191074).Curated1
Sequence conflicti611A → V in CAD97914 (PubMed:17974005).Curated1
Sequence conflicti616S → I in CAA64700 (PubMed:9191074).Curated1
Sequence conflicti820G → E in CAD97914 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04213881N → T1 PublicationCorresponds to variant dbSNP:rs33932471Ensembl.1
Natural variantiVAR_042139235S → A1 PublicationCorresponds to variant dbSNP:rs55710198Ensembl.1
Natural variantiVAR_042140330E → Q1 PublicationCorresponds to variant dbSNP:rs56205382Ensembl.1
Natural variantiVAR_042141417R → Q in a lung adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs199614818Ensembl.1
Natural variantiVAR_042142503E → K in a lung large cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_045912506Y → C1 PublicationCorresponds to variant dbSNP:rs56074660Ensembl.1
Natural variantiVAR_042143582G → E in a lung adenocarcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1057520012Ensembl.1
Natural variantiVAR_042144672A → T1 PublicationCorresponds to variant dbSNP:rs36050417Ensembl.1
Natural variantiVAR_042145673S → T1 PublicationCorresponds to variant dbSNP:rs56359290Ensembl.1
Natural variantiVAR_042146856T → I in a lung squamous cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042147959H → R1 PublicationCorresponds to variant dbSNP:rs56312931Ensembl.1
Natural variantiVAR_0421481032N → S in a lung large cell carcinoma sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0391181 – 69Missing in isoform 3. 1 PublicationAdd BLAST69
Alternative sequenceiVSP_039119563F → SV in isoform 3. 1 Publication1
Alternative sequenceiVSP_002999597 – 619SCCEC…PSLIW → R in isoform 2. CuratedAdd BLAST23

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X95425 mRNA Translation: CAA64700.1
AC018683 Genomic DNA No translation available.
AC104137 Genomic DNA No translation available.
AC105923 Genomic DNA No translation available.
AC115223 Genomic DNA No translation available.
BX537946 mRNA Translation: CAD97914.1
L36644 mRNA Translation: AAA74245.1
CCDSiCCDS3513.1 [P54756-1]
CCDS3514.1 [P54756-2]
RefSeqiNP_001268694.1, NM_001281765.2
NP_001268695.1, NM_001281766.2
NP_001305690.1, NM_001318761.1 [P54756-3]
NP_004430.4, NM_004439.7 [P54756-1]
NP_872272.2, NM_182472.4 [P54756-2]
UniGeneiHs.654492

Genome annotation databases

EnsembliENST00000273854; ENSP00000273854; ENSG00000145242 [P54756-1]
ENST00000354839; ENSP00000346899; ENSG00000145242 [P54756-2]
GeneIDi2044
KEGGihsa:2044
UCSCiuc003hcy.5 human [P54756-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiEPHA5_HUMAN
AccessioniPrimary (citable) accession number: P54756
Secondary accession number(s): Q7Z3F2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: September 22, 2009
Last modified: July 18, 2018
This is version 184 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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