Protein detail

EPHA4

Ephrin type-A receptor 4 (EC 2.7.10.1) (EPH-like kinase 8) (EK8) (hEK8) (Tyrosine-protein kinase TYRO1) (Tyrosine-protein kinase receptor SEK)

Entry name EPHA4	UniProt ID P54764	EVMP confidence score 0.63
Supporting publications (n) 24	Transmembrane count 1	Protein classification Cancer-related genesEnzymesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

Protein Names

Ephrin type-A receptor 4 (EC 2.7.10.1) (EPH-like kinase 8) (EK8) (hEK8) (Tyrosine-protein kinase TYRO1) (Tyrosine-protein kinase receptor SEK)

Protein Class (5)

Cancer-related genesEnzymesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins

Protein Function (5)

Predicted intracellular proteins
ENZYME proteins:Transferases
Enzymes
Cancer-related genes:Candidate cancer biomarkers
Kinases:Tyr protein kinases

Transmembrane

548..569; Helical

Transmembrane Count

Ensembl

ENSG00000116106

Entrez Gene Symbol

EPHA4

Gene Synonym (2)

Hek8TYRO1

Gene Description

EPH receptor A4

Chromosome

Position

221418027-221574202

Supporting publications (n)

EVMP confidence score

0.63

Fluorescence & Localization2

Cell SpecificNeutrophilsBlood Cell Specificneutrophil

Function & Pathway8

Protein Function (5)

Predicted intracellular proteins
ENZYME proteins:Transferases
Enzymes
Cancer-related genes:Candidate cancer biomarkers
Kinases:Tyr protein kinases

Cellular Component (19)

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Molecular Function (13)

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Biological Process (3)

KEGG

hsa04360 Axon guidance

Reactome (7)

Canonical Pathways (2)

M247 Pid insulin glucose pathway
M7955 Sig insulin receptor pathway in cardiac myocytes

Mediation Categories (4)

Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationReceptor-signaling mediation

Relations & Evidence88

Enzyme-Mediated Modification (1)

1 record.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
EPHA4	PTPRO	Q16827	Y	602	phosphorylation	KEA	KEA:11136979

Ligand-Receptor Signaling (70)

70 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
extracellular	extracellular	HPMR	No	No	No	Yes	No
extracellular	extracellular	OmniPath	No	No	No	Yes	No
intracellular	intracellular	LOCATE	No	No	No	Yes	No
intracellular	intracellular	ComPPI	No	No	No	Yes	No
intracellular	intracellular	GO_Intercell	No	No	No	Yes	No
intracellular	intracellular	UniProt_location	No	No	No	Yes	No
intracellular	intracellular	OmniPath	No	No	No	Yes	No
cell_surface_ligand	cell_surface_ligand	connectomeDB2020	Yes	No	No	Yes	No
cell_surface_ligand	cell_surface_ligand	Baccin2019	Yes	No	No	Yes	No
cell_surface_ligand	cell_surface_ligand	OmniPath	Yes	No	No	Yes	No

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Regulatory Interaction Network (12)

12 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
EFNB3	Q15768	EPHA4	P54764	Yes	Yes	No	iTALKICELLNETSIGNORHINTCellPhoneDB_CellinkerDIPHPMR_talklrCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDIntActDLRP_talklrRamilowski2015_Baccin2019WangRamilowski2015HPMR_LRdbCellPhoneDBHPRD_talklrBioGRIDBaccin2019CellinkerSTRING_talklrEMBRACECellTalkDBFantom5_LRdbHPMR_CellinkerconnectomeDB2020LRdb	HINT:9484836 connectomeDB2020:12383247 Cellinker:12383247 Cellinker:9484836 Cellinker:15114347 IntAct:23812375 BioGRID:9484836 Baccin2019:12649481 Baccin2019:12383247 DIP:23812375 connectomeDB2020:9484836 CellChatDB:15114347 HPRD:9484836 Cellinker:12649481 Baccin2019:9484836 LRdb:12094214 HINT:33961781 HPRD:12383247 HINT:23812375 ICELLNET:24003208 SIGNOR:9330863 ICELLNET:15114347
EFNA3	P52797	EPHA4	P54764	Yes	Yes	No	iTALKICELLNETSIGNORCellPhoneDB_CellinkerHPMR_talklrCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDRamilowski2015_Baccin2019DLRP_talklrWangRamilowski2015HPMR_LRdbCellPhoneDBHPRD_talklrBaccin2019CellinkerSTRING_talklrEMBRACECellCallCellTalkDBFantom5_LRdbHPMR_CellinkerconnectomeDB2020LRdb	HPRD:12496762 ICELLNET:24003208 connectomeDB2020:12496762 SIGNOR:9330863 Cellinker:15114347 LRdb:11114742 ICELLNET:15114347 CellChatDB:15114347Baccin2019:933086312496762connectomeDB2020:9330863

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Protein Complex Composition (4)

4 records.

Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs
EIF3A EIF3B EIF3F EIF3H EIF3J EIF4A1 EIF4A2 EIF4E EIF4G1 EIF4G2 EIF4G3 EPHA4 NCBP1 PABPC1 UBC	O00303 O15372 O43432 O75822 P06730 P0CG48 P11940 P54764 P55884 P60842 P78344 Q04637 Q09161 Q14152 Q14240	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC8104
EFNA2 EPHA4	O43921 P54764	1:1	PDB	PDB:2wo3
EPHA4	P54764	2	PDB	PDB:5jr2PDB:2wo1PDB:4w4zPDB:4bk4PDB:3ckhPDB:4w50
EFNB3 EPHA4	P54764 Q15768	2:2	PDB	PDB:4bkf

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
PRotein Organic Solvent Precipitation；Differential Ultracentrifugation	Mass spectrometry	1	32384937

Sequence, Structure & Domains14

Sequences

Length

986

Mass

109,860

Sequence

MAGIFYFALFSCLFGICDAVTGSRVYPANEVTLLDSRSVQGELGWIASPLEGGWEEVSIMDEKNTPIRTYQVCNVMEPSQNNWLRTDWITREGAQRVYIEIKFTLRDCNSLPGVMGTCKETFNLYYYESDNDKERFIRENQFVKIDTIAADESFTQVDIGDRIMKLNTEIRDVGPLSKKGFYLAFQDVGACIALVSVRVFYKKCPLTVRNLAQFPDTITGADTSSLVEVRGSCVNNSEEKDVPKMYCGADGEWLVPIGNCLCNAGHEERSGECQACKIGYYKALSTDATCAKCPPHSYSVWEGATSCTCDRGFFRADNDAASMPCTRPPSAPLNLISNVNETSVNLEWSSPQNTGGRQDISYNVVCKKCGAGDPSKCRPCGSGVHYTPQQNGLKTTKVSITDLLAHTNYTFEIWAVNGVSKYNPNPDQSVSVTVTTNQAAPSSIALVQAKEVTRYSVALAWLEPDRPNGVILEYEVKYYEKDQNERSYRIVRTAARNTDIKGLNPLTSYVFHVRARTAAGYGDFSEPLEVTTNTVPSRIIGDGANSTVLLVSVSGSVVLVVILIAAFVISRRRSKYSKAKQEADEEKHLNQGVRTYVDPFTYEDPNQAVREFAKEIDASCIKIEKVIGVGEFGEVCSGRLKVPGKREICVAIKTLKAGYTDKQRRDFLSEASIMGQFDHPNIIHLEGVVTKCKPVMIITEYMENGSLDAFLRKNDGRFTVIQLVGMLRGIGSGMKYLSDMSYVHRDLAARNILVNSNLVCKVSDFGMSRVLEDDPEAAYTTRGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVIKAIEEGYRLPPPMDCPIALHQLMLDCWQKERSDRPKFGQIVNMLDKLIRNPNSLKRTGTESSRPNTALLDPSSPEFSAVVSVGDWLQAIKMDRYKDNFTAAGYTTLEAVVHVNQEDLARIGITAITHQNKILSSVQAMRTQMQQMHGRMVPV

Alternative Products

Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P54764-1; Sequence=Displayed; Name=2; IsoId=P54764-2; Sequence=VSP_056016

Alternative Sequence

1..53; MAGIFYFALFSCLFGICDAVTGSRVYPANEVTLLDSRSVQGELGWIASPLEGG -> MK (in isoform 2)

3D Structural Models

Turn

40..42; 373..375; 538..540

Helix

36..38; 108..110; 139..141; 426..428

Beta Strand

29..35; 46..53; 55..60; 62..65; 66..72; 77..79; 82..85; 93..96; 97..105; 114..116; 119..130; 131..133; 142..149; 154..159; 162..173; 178..190; 192..203; 207..209; 212..214; 226..230; 237..248; 257..262; 266..269; 272..275; 304..306; 333..340; 343..349; 361..368; 385..388; 390..393; 395..401; 405..416; 418..423; 429..435; 447..452; 457..461; 473..483; 489..500; 508..517; 528..531

3D Structure

NMR spectroscopy (1); X-ray crystallography (16)

Domain & Motif Annotations

Motif

984..986; PDZ-binding

Domain (CC)

The protein kinase domain mediates interaction with NGEF.

Domain (FT)

30..209; Eph LBD; 328..439; Fibronectin type-III 1; 440..537; Fibronectin type-III 2; 621..882; Protein kinase; 911..975; SAM

Protein Families (3)

Protein kinase superfamily
Tyr protein kinase family
Ephrin receptor subfamily

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.

Clinical Relevance8

Disease Involvement

Cancer-related genes

Related Diseases

Solid tumour/cancer

Biomarker

Terminated

Drugs

VANDETANIB

Antibody

CAB028368

Interaction Protein (4)

ENSG00000108947ENSG00000133216ENSG00000184349ENSG00000243364

Interaction Count

Interaction Dataset

intact_biogrid

Supporting Publications24

PMID	Title	Abstract
32795414	Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.	Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers.
34889606	Surface Nanosieving Polyether Sulfone Particles with Graphene Oxide Encapsulation for the Negative Isolation toward Extracellular Vesicles.	No abstract available
36635400	Proteomic profiling of urinary small extracellular vesicles in children with pneumonia: a pilot study.	No abstract available
37686366	Identification of a Non-Invasive Urinary Exosomal Biomarker for Diabetic Nephropathy Using Data-Independent Acquisition Proteomics.	No abstract available
38136601	Identification of Central Nervous System Oncologic Disease Biomarkers in EVs from Cerebrospinal Fluid (CSF) of Pediatric Patients: A Pilot Neuro-Proteomic Study.	No abstract available
38225453	Deep proteomic analysis of obstetric antiphospholipid syndrome by DIA-MS of extracellular vesicle enriched fractions.	No abstract available
39022990	Placenta-derived mesenchymal stem cells promote diabetic wound healing via exosomal protein interaction networks.	No abstract available
39290459	Urinary extracellular vesicles as a monitoring tool for renal damage in patients not meeting criteria for chronic kidney disease.	No abstract available
39949490	CRISPR-dCas9 Activation of TSG-6 in MSCs Modulates the Cargo of MSC-Derived Extracellular Vesicles and Attenuates Inflammatory Responses in Human Intervertebral Disc Cells In Vitro.	No abstract available
40098346	Toward Identification of Markers for Brain-Derived Extracellular Vesicles in Cerebrospinal Fluid: A Large-Scale, Unbiased Analysis Using Proximity Extension Assays.	No abstract available

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