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 | EVMP confidence score 0.88 |
Supporting publications (n) 24 | Transmembrane count 1 | Protein classification Cancer-related genesEnzymesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins |
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.70High >= 0.60Medium >= 0.40Low >= 0.30Basic Information
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
1
Ensembl
Entrez Gene Symbol
Gene Synonym (2)
Hek8TYRO1
Gene Description
EPH receptor A4
Chromosome
2
Position
221418027-221574202
Supporting publications (n)
24
EVMP confidence score
0.88
Fluorescence & Localization
Cell SpecificNeutrophilsBlood Cell Specificneutrophil
Function & Pathway
Protein Function (5)
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Kinases:Tyr protein kinases
Cellular Component (19)
- GO:0005737 cytoplasm
- GO:0005741 mitochondrial outer membrane
- GO:0005886 plasma membrane
- GO:0005912 adherens junction
- GO:0009986 cell surface
- GO:0030175 filopodium
- GO:0030424 axon
- GO:0030425 dendrite
- GO:0031594 neuromuscular junction
- GO:0031901 early endosome membrane
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Molecular Function (13)
- GO:0001540 amyloid-beta binding
- GO:0004672 protein kinase activity
- GO:0004713 protein tyrosine kinase activity
- GO:0005004 GPI-linked ephrin receptor activity
- GO:0005005 transmembrane-ephrin receptor activity
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0016301 kinase activity
- GO:0042731 PH domain binding
- GO:0042802 identical protein binding
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Biological Process (3)
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 | Yes | ||||
| extracellular | extracellular | OmniPath | Yes | ||||
| intracellular | intracellular | LOCATE | Yes | ||||
| intracellular | intracellular | ComPPI | Yes | ||||
| intracellular | intracellular | GO_Intercell | Yes | ||||
| intracellular | intracellular | UniProt_location | Yes | ||||
| intracellular | intracellular | OmniPath | Yes | ||||
| cell_surface_ligand | cell_surface_ligand | connectomeDB2020 | Yes | Yes | |||
| cell_surface_ligand | cell_surface_ligand | Baccin2019 | Yes | Yes | |||
| cell_surface_ligand | cell_surface_ligand | OmniPath | Yes | Yes |
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 |
|---|---|---|---|---|---|---|---|---|
| EFNA1 | P20827 | EPHA4 | P54764 | Yes | Yes | iTALKICELLNETSIGNORCellPhoneDB_CellinkerSignaLink3DIPLit-BM-17HPMR_talklrCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDRamilowski2015_Baccin2019DLRP_talklrWangRamilowski2015HPMR_LRdbCellPhoneDBHPRD_talklrBaccin2019CellinkerSTRING_talklrEMBRACECellCallCellTalkDBFantom5_LRdbHPMR_CellinkerconnectomeDB2020SPIKE_LCLRdb | connectomeDB2020:9330863Lit-BM-17:19836338connectomeDB2020:8755474ICELLNET:24003208Lit-BM-17:10366629HPRD:8755474Cellinker:15114347DIP:19836338SIGNOR:9330863LRdb:11114742CellChatDB:15114347ICELLNET:15114347SignaLink3:9576626SignaLink3:23331499SIGNOR:9576626Baccin2019:9330863SPIKE_LC:16189514 | |
| EFNA5 | P52803 | EPHA4 | P54764 | Yes | Yes | iTALKICELLNETSIGNORHINTCellPhoneDB_CellinkerSignaLink3DIPHPMR_talklrHPMRCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDIntActDLRP_talklrRamilowski2015_Baccin2019WangRamilowski2015HPMR_LRdbCellPhoneDBHPRD_talklrBaccin2019CellinkerSTRING_talklrEMBRACECellCallCellTalkDBFantom5_LRdbHPMR_CellinkerconnectomeDB2020LRdb | Cellinker:15114347HINT:19836338IntAct:23812375Baccin2019:9330863connectomeDB2020:8755474SignaLink3:8755474SignaLink3:18988627DIP:23812375LRdb:11114742CellChatDB:15114347SignaLink3:23331499HINT:23959867connectomeDB2020:9330863HINT:33961781HINT:23812375HPMR:9330863ICELLNET:24003208IntAct:19836338HPRD:8755474SIGNOR:9330863DIP:19836338ICELLNET:15114347SignaLink3:9576626 | |
| EPHA4 | P54764 | NGEF | Q8N5V2 | Yes | Yes | PhosphoPointHPRDSignaLink3WangSPIKE_LC | SignaLink3:23331499HPRD:11336673SignaLink3:11336673SignaLink3:21071413SPIKE_LC:16189514 | |
| EFNA4 | P52798 | EPHA4 | P54764 | Yes | Yes | iTALKICELLNETHINTCellPhoneDB_CellinkerSignaLink3DIPCellChatDBHPRD_LRdbDLRP_CellinkertalklrHPRDRamilowski2015_Baccin2019DLRP_talklrRamilowski2015CellPhoneDBHPRD_talklrBaccin2019CellinkerEMBRACECellCallCellTalkDBFantom5_LRdbconnectomeDB2020LRdb | ICELLNET:24003208Cellinker:15114347DIP:19836338HPRD:10366629LRdb:11114742HINT:19836338CellChatDB:15114347ICELLNET:15114347SignaLink3:23331499SignaLink3:9267020Baccin2019:10366629connectomeDB2020:10366629HINT:33961781 | |
| EPHA4 | P54764 | ARHGF | O94989 | Yes | Yes | PhosphoPointHPRDSignaLink3WangSPIKE_LC | SignaLink3:23331499SignaLink3:12775584HPRD:12775584SPIKE_LC:16189514 | |
| EPHA4 | P54764 | FYN | P06241 | Yes | Yes | PhosphoPointHPRDSignaLink3WangSPIKE_LC | SignaLink3:23331499SignaLink3:12084815HPRD:12084815SPIKE_LC:16713569 | |
| EPHA4 | P54764 | GHR | P10912 | Yes | Yes | SIGNOR | SIGNOR:28686668 | |
| EPHA4 | P54764 | STA5B | P51692 | Yes | Yes | SIGNOR | SIGNOR:28686668 | |
| EPHA4 | P54764 | JAK2 | O60674 | Yes | Yes | SIGNOR | SIGNOR:28686668 | |
| EFNA2 | O43921 | EPHA4 | P54764 | Yes | Yes | iTALKICELLNETSIGNORHINTCellPhoneDB_CellinkerDIPLit-BM-17HPMR_talklrCellChatDBDLRP_CellinkertalklrIntActDLRP_talklrRamilowski2015_Baccin2019WangRamilowski2015HPMR_LRdbCellPhoneDBBaccin2019CellinkerSTRING_talklrEMBRACECellCallCellTalkDBFantom5_LRdbHPMR_CellinkerconnectomeDB2020LRdb | connectomeDB2020:9330863Lit-BM-17:19836338ICELLNET:24003208IntAct:19836338SIGNOR:9330863Cellinker:15114347DIP:19836338LRdb:11114742HINT:19836338CellChatDB:15114347ICELLNET:15114347Baccin2019:9330863 |
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Protein Complex Composition (4)
4 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| EIF3AEIF3BEIF3FEIF3HEIF3JEIF4A1EIF4A2EIF4EEIF4G1EIF4G2EIF4G3EPHA4NCBP1PABPC1UBC | O00303O15372O43432O75822P06730P0CG48P11940P54764P55884P60842P78344Q04637Q09161Q14152Q14240 | 1:1:1:1:1:1:1:1:1:1:1:1:1:1:1 | NetworkBlastCompleat | Compleat:HC8104 | ||
| EFNA2EPHA4 | O43921P54764 | 1:1 | PDB | PDB:2wo3 | ||
| EPHA4 | P54764 | 2 | PDB | PDB:5jr2PDB:2wo1PDB:4w4zPDB:4bk4PDB:3ckhPDB:4w50 | ||
| EFNB3EPHA4 | P54764Q15768 | 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 & Domains
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 Relevance
Disease Involvement
Cancer-related genes
Related Diseases
Biomarker
Terminated
Drugs
Antibody
Interaction Protein (4)
ENSG00000108947ENSG00000133216ENSG00000184349ENSG00000243364
Interaction Count
4
Interaction Dataset
intact_biogrid
Supporting Publications24
| PMID | Title | Related sentences |
|---|---|---|
| 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 related sentences available |
| 36635400 | Proteomic profiling of urinary small extracellular vesicles in children with pneumonia: a pilot study. | No related sentences available |
| 37686366 | Identification of a Non-Invasive Urinary Exosomal Biomarker for Diabetic Nephropathy Using Data-Independent Acquisition Proteomics. | No related sentences 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 related sentences available |
| 38225453 | Deep proteomic analysis of obstetric antiphospholipid syndrome by DIA-MS of extracellular vesicle enriched fractions. | No related sentences available |
| 39022990 | Placenta-derived mesenchymal stem cells promote diabetic wound healing via exosomal protein interaction networks. | No related sentences available |
| 39290459 | Urinary extracellular vesicles as a monitoring tool for renal damage in patients not meeting criteria for chronic kidney disease. | No related sentences 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 related sentences available |
| 40098346 | Toward Identification of Markers for Brain-Derived Extracellular Vesicles in Cerebrospinal Fluid: A Large-Scale, Unbiased Analysis Using Proximity Extension Assays. | No related sentences available |