Home
GeneCards Guide
Suite
- MalaCards
- GeneALaCart
- GeneDecks
- GeneIP
- GeneLoc
Terms and Conditions
- Terms of Use
- 3rd Party Notice
About Us
User Feedback
Mirror sites

Set Analyses:

Generates a file of GeneCards annotations for your list of genes

Advanced Search

Search By

Section (entire)

for

All GeneCards Within gene subset (to enable gene prioritization):
or upload a file of gene symbols

Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

EPHA4 Gene

protein-coding GIFtS: 68
GCID: GC02M222248

EPH receptor A4

(Previous name: EphA4 )
(Previous symbol: TYRO1)

Explore 20 diseases affiliated with
EPHA4 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
EPH Receptor A4¹ ²		EC 2.7.10.1³ ⁸
TYRO1¹ ² ³		EphA4¹
Tyrosine-Protein Kinase Receptor SEK² ³		Hek8¹
Tyrosine-Protein Kinase TYRO1² ³		Ephrin Type-A Receptor 4²
EK8² ³		Receptor Protein-Tyrosine Kinase HEK8²
HEK8² ³		TYRO1 Protein Tyrosine Kinase²
SEK² ³		HEK8² ³
EPH-Like Kinase 8² ³		EC 2.7.10⁸

External Ids:	HGNC: 3388¹	Entrez Gene: 2043²	Ensembl: ENSG00000116106⁷	OMIM: 602188⁵	UniProtKB: P54764³

Export aliases for EPHA4 gene to outside databases

Previous GC identifers: GC02M220313 GC02M221011 GC02M222492 GC02M222108 GC02M221990 GC02M214137

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for EPHA4:

This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors

have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH

subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2

fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their

extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. (provided by RefSeq,

Jul 2008)

UniProtKB/Swiss-Prot: EPHA4_HUMAN, P54764

Function: Receptor tyrosine kinase which binds membrane-bound ephrin 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. Highly promiscuous, it has the unique property among Eph receptors to bind and to be

physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3.

Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation

of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling

different steps of axonal guidance including the establishment of the corticospinal projections. May also control the

segregation of motor and sensory axons during neuromuscular circuit development. Beside its role in axonal guidance

plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates

NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, plays also a role in repair after

injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation.

Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for

instance the development of the thymic epithelium

Gene Wiki entry for EPHA4 (EPH receptor A4)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000002.11 NC_018913.1 NT_005403.17

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the EPHA4 gene promoter:
Nkx3-1 Sox5 Nkx3-1 v4 STAT1 Nkx3-1 v1 Nkx3-1 v2 FOXC1 STAT3 Nkx3-1 v3
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: EPHA4 promoter sequence

Search SABiosciences Chromatin IP Primers for EPHA4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat EPHA4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q36.1 Ensembl cytogenetic band: 2q36.1 HGNC cytogenetic band: 2q36.3

EPHA4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
EPHA4 gene location

GeneLoc information about chromosome 2 GeneLoc Exon Structure

GeneLoc location for GC02M222248: view genomic region (about GC identifiers)

Start:	222,282,747 bp from pter	End:	222,438,922 bp from pter
Size:	156,176 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: EPHA4_HUMAN, P54764 (See protein sequence)

Recommended Name: Ephrin type-A receptor 4 precursor

Size: 986 amino acids; 109860 Da

Subunit: 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. Interacts (phosphorylated at position

Tyr-602) with FYN. Interacts with CDK5, CDK5R1 and NGEF; upon activation by EFNA1 induces NGEF phosphorylation by the

kinase CDK5. Interacts with CHN1; effector of EPHA4 in axon guidance linking EPHA4 activation to RAC1 regulation (By

similarity). Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation

of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases

Subcellular location: Cell membrane; Single-pass type I membrane protein (By similarity). Cell projection, axon (By

similarity). Cell projection, dendrite (By similarity). Cell junction, synapse, postsynaptic cell membrane,

postsynaptic density (By similarity). Early endosome (By similarity). Note=Clustered upon activation and targeted to

early endosome (By similarity)

5 PDB 3D structures from and Proteopedia for EPHA4:

2WO1 (3D)

2WO2 (3D)

2WO3 (3D)

3CKH (3D)

3GXU (3D)

Secondary accessions: Q2M380

Explore the universe of human proteins at neXtProt for EPHA4: NX_P54764

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P54764

4/53 DME Specific Peptides for EPHA4 (P54764) (see all 53)

MSNQDVI

KERFIRE

PVMIITE

RDLAARN

EPHA4 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_004429.1

ENSEMBL proteins:

ENSP00000386276 ENSP00000386829 ENSP00000408145 ENSP00000395917 ENSP00000401405

ENSP00000391517 ENSP00000410158 ENSP00000444085 ENSP00000404089 ENSP00000281821

ENSP00000375923

Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant EPHA4 Protein
	R&D Systems Recombinant & Natural Proteins for EPHA4
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells Browse OriGene Protein Over-expression Lysates OriGene Custom Protein Services for EPHA4
	GenScript Custom Purified and Recombinant Proteins Services for EPHA4
	Novus Biologicals EPHA4 Proteins
	Sino Biological Recombinant Protein for EPHA4
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for EPHA4

Gene Ontology (GO): 5/17 cellular component terms (GO ID links to tree view) (see all 17): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	ISS	--
GO:0005741	mitochondrial outer membrane	IEA	--
GO:0005783	endoplasmic reticulum	IEA	--
GO:0005794	Golgi apparatus	IEA	--
GO:0005887	integral to plasma membrane	ISS	--

EPHA4 for ontologies About GeneDecksing

EPHA4 Antibody Products:

	Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	R&D Systems Antibodies for EPHA4
	Cell Signaling Technology (CST) Antibodies for EPHA4
	Browse OriGene Antibodies OriGene Custom Antibody Services for EPHA4
	GenScript Custom Superior Antibodies Services for EPHA4
	Novus Biologicals EPHA4 Antibodies
	Abcam antibodies for EPHA4
	Uscn Antibodies for EPHA4
	ThermoFisher Antibody for EPHA4

Assay Products for EPHA4:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems Multiplex/Array Assay Kits & Reagents for EPHA4
	GenScript Custom Assay Services for EPHA4
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for EPHA4

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

EPHA4 for domains About GeneDecksing

5/15 InterPro domains/families (see all 15):

IPR017441 Protein_kinase_ATP_BS

IPR013761 SAM/pointed

IPR001660 SAM

IPR011510 SAM_2

IPR001245 Ser-Thr/Tyr_kinase_cat_dom

Graphical View of Domain Structure for InterPro Entry P54764

ProtoNet protein and cluster: P54764

5/6 Blocks protein families (see all 6):

IPB001090 Ephrin receptor

IPB001426 Receptor tyrosine kinase

IPB001660 Sterile alpha motif SAM

IPB003962 Fibronectin type III repeat signature

IPB008266 Tyrosine protein kinase

UniProtKB/Swiss-Prot: EPHA4_HUMAN, P54764

Domain: The protein kinase domain mediates interaction with NGEF (By similarity)

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

Similarity: Contains 1 Eph LBD (Eph ligand-binding) domain

Similarity: Contains 2 fibronectin type-III domains

Similarity: Contains 1 protein kinase domain

Similarity: Contains 1 SAM (sterile alpha motif) domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: