EPHA4 EPH receptor A4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EPHA4provided by HGNC
Official Full Name: EPH receptor A4provided by HGNC
Primary source: HGNC:HGNC:3388
See related: Ensembl:ENSG00000116106 MIM:602188
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EK8; SEK; HEK8; TYRO1
Summary: 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]
Expression: Broad expression in brain (RPKM 16.1), testis (RPKM 9.3) and 17 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q36.1

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
109.20211119	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (221418027..221574202, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (222282747..222438922, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Exosomal miR-106b-5p derived from melanoma cell promotes primary melanocytes epithelial-mesenchymal transition through targeting EphA4.
Title: Exosomal miR-106b-5p derived from melanoma cell promotes primary melanocytes epithelial-mesenchymal transition through targeting EphA4.
A cancer mutation promotes EphA4 oligomerization and signaling by altering the conformation of the SAM domain.
Title: A cancer mutation promotes EphA4 oligomerization and signaling by altering the conformation of the SAM domain.
EphA4 regulates Abeta production via BACE1 expression in neurons.
Title: EphA4 regulates Aβ production via BACE1 expression in neurons.
Ephrin Receptor A4 Expression Enhances Migration, Invasion and Neurotropism in Pancreatic Ductal Adenocarcinoma Cells.
Title: Ephrin Receptor A4 Expression Enhances Migration, Invasion and Neurotropism in Pancreatic Ductal Adenocarcinoma Cells.
EPHA4 signaling might function to maintain homeostasis of vascular smooth muscle cell contractility and BP in a fine-tuning capacity, for which estrogen is an effective modifier.
Title: EPHA4 regulates vascular smooth muscle cell contractility and is a sex-specific hypertension risk gene in individuals with type 2 diabetes.
Overall, these findings implicate EphA4 as a novel mediator of cortical tissue damage and neuroinflammation following traumatic brain injury.
Title: Peripheral loss of EphA4 ameliorates TBI-induced neuroinflammation and tissue damage.
MiR-145 exerted a protective effects in cell viability in the OGD model by downregulating EPHA4, which suggested their potential roles in ischemic stroke.
Title: MiR-145 protected the cell viability of human cerebral cortical neurons after oxygen-glucose deprivation by downregulating EPHA4.
blockage of EphA4/ephrin signaling between neuron and microglia decreased in oxygen-glucose deprivation and reperfusion -induced injury by promoting alternative activation of microglia via RhoA/ROCK2 signaling.
Title: Neuronal EphA4 Regulates OGD/R-Induced Apoptosis by Promoting Alternative Activation of Microglia.
our data revealed a strong association between high EPHA4 expression and advanced tumor stage, aggressive BLBC molecular subtype and poor prognosis. Importantly, we found significant co-expression of EPHA4 and the TGFbeta receptor type-2 (TGFbetaR2) in breast cancer subtypes associated with increased tumor relapse and drug resistance.
Title: Transforming Growth Factor-beta Regulation of Ephrin Type-A Receptor 4 Signaling in Breast Cancer Cellular Migration.
Taken together, these results identify EphA4 as a new entry receptor for Kaposi's sarcoma-associated herpesvirus.
Title: Ephrin Receptor A4 is a New Kaposi's Sarcoma-Associated Herpesvirus Virus Entry Receptor.

Submit: New GeneRIF Correction See all GeneRIFs (50)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy. GeneReviews: Not available
Genome-wide SNP associations with rubella-specific cytokine responses in measles-mumps-rubella vaccine recipients. GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-24374 (e-PCR)
- UniSTS:99864

RH70277 (e-PCR)
- UniSTS:32538

RH78262 (e-PCR)
- UniSTS:18225

MARC_49122-49123:1117732036:1 (e-PCR)
- UniSTS:477489

EPHA4_1970 (e-PCR)
- UniSTS:280656

RH12531 (e-PCR)
- UniSTS:76116

RH93447 (e-PCR)
- UniSTS:84331

A004S26 (e-PCR)
- UniSTS:73092

RH46518 (e-PCR)
- UniSTS:62385

NoName (e-PCR)
- UniSTS:484284

STS-T47772 (e-PCR)
- UniSTS:54495

Homology

Homologs of the EPHA4 gene: The EPHA4 gene is conserved in chimpanzee, Rhesus monkey, dog, mouse, rat, chicken, zebrafish, C.elegans, and frog.
Orthologs from Annotation Pipeline: 380 organisms have orthologs with human gene EPHA4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DH domain binding	IDA Inferred from Direct Assay more info	PubMed
enables GPI-linked ephrin receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables PH domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables amyloid-beta binding	TAS Traceable Author Statement more info	PubMed
enables ephrin receptor binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables kinase activity	IGI Inferred from Genetic Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine/tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables transmembrane-ephrin receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables transmembrane-ephrin receptor activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in adherens junction organization	IEA Inferred from Electronic Annotation more info
involved_in adult walking behavior	IEA Inferred from Electronic Annotation more info
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amyloid-beta	ISS Inferred from Sequence or Structural Similarity more info
involved_in cochlea development	IEA Inferred from Electronic Annotation more info
involved_in corticospinal tract morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in ephrin receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in fasciculation of motor neuron axon	ISS Inferred from Sequence or Structural Similarity more info
involved_in fasciculation of sensory neuron axon	ISS Inferred from Sequence or Structural Similarity more info
involved_in glial cell migration	IEA Inferred from Electronic Annotation more info
involved_in motor neuron axon guidance	ISS Inferred from Sequence or Structural Similarity more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in negative regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of axon regeneration	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of cellular response to hypoxia	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of epithelial to mesenchymal transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of long-term synaptic potentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of proteolysis involved in cellular protein catabolic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in nephric duct morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in neuron projection fasciculation	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron projection guidance	ISS Inferred from Sequence or Structural Similarity more info
involved_in peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of JUN kinase activity	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of Rho guanyl-nucleotide exchange factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of amyloid-beta formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of dendrite morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in positive regulation of protein tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein stabilization	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of GTPase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of astrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of axonogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of dendritic spine morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of modification of synaptic structure	ISS Inferred from Sequence or Structural Similarity more info
involved_in synapse pruning	IEA Inferred from Electronic Annotation more info
involved_in transmembrane receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in Schaffer collateral - CA1 synapse	IEA Inferred from Electronic Annotation more info
located_in adherens junction	IEA Inferred from Electronic Annotation more info
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in axon terminus	IEA Inferred from Electronic Annotation more info
located_in axonal growth cone	IEA Inferred from Electronic Annotation more info
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in dendritic shaft	ISS Inferred from Sequence or Structural Similarity more info
is_active_in dendritic spine	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in dendritic spine	ISS Inferred from Sequence or Structural Similarity more info
located_in early endosome membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in filopodium	IEA Inferred from Electronic Annotation more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in integral component of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in integral component of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in integral component of postsynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in integral component of presynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrial outer membrane	IEA Inferred from Electronic Annotation more info
located_in neuromuscular junction	IEA Inferred from Electronic Annotation more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in perikaryon	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic density membrane	IEA Inferred from Electronic Annotation more info
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: ephrin type-A receptor 4

Names: EPH-like kinase 8; TYRO1 protein tyrosine kinase; receptor protein-tyrosine kinase HEK8; tyrosine-protein kinase TYRO1; tyrosine-protein kinase receptor SEK

NP_001291465.1

EC 2.7.10.1

NP_001291466.1

EC 2.7.10.1

NP_001350677.1

EC 2.7.10.1

NP_004429.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001304536.2 → NP_001291465.1 ephrin type-A receptor 4 isoform a precursor

See identical proteins and their annotated locations for NP_001291465.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Variants 1 and 2 both encode the same isoform (a).

Source sequence(s)

AC010899, AK290306, BC105000, BM676153

Consensus CDS

CCDS2447.1

UniProtKB/Swiss-Prot

P54764

UniProtKB/TrEMBL

A0A024R452

Related

ENSP00000386829.1, ENST00000409938.5

Conserved Domains (5) summary

cd09545
Location:911 → 981

SAM_EPH-A4; SAM domain of EPH-A4 subfamily of tyrosine kinase receptors

cd10482
Location:30 → 203

EphR_LBD_A4; Ligand Binding Domain of Ephrin type-A Receptor 4

cd00063
Location:441 → 532

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05066
Location:616 → 882

PTKc_EphR_A; Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors

pfam14575
Location:562 → 618

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
NM_001304537.2 → NP_001291466.1 ephrin type-A receptor 4 isoform b

See identical proteins and their annotated locations for NP_001291466.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant (1). The resulting isoform (b) has a shorter and distinct N-terminus compared to isoform a.

Source sequence(s)

AC010899, AK300772, BC105000, BM676153, DA451606

UniProtKB/Swiss-Prot

P54764

Conserved Domains (7) summary

cd09545
Location:860 → 930

SAM_EPH-A4; SAM domain of EPH-A4 subfamily of tyrosine kinase receptors

smart00454
Location:864 → 924

SAM; Sterile alpha motif

cd10473
Location:3 → 152

EphR_LBD_A; Ligand Binding Domain of Ephrin type-A Receptors

cd00063
Location:390 → 481

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05066
Location:565 → 831

PTKc_EphR_A; Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors

pfam07714
Location:570 → 827

Pkinase_Tyr; Protein tyrosine kinase

pfam14575
Location:511 → 565

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
NM_001363748.2 → NP_001350677.1 ephrin type-A receptor 4 isoform c precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and 3' coding sequence compared to variant (1). The resulting isoform (c) has a shorter and distinct C-terminus compared to isoform a.

Source sequence(s)

AC010899, AC079834

Consensus CDS

CCDS86924.1

Related

ENSP00000386276.1, ENST00000409854.5

Conserved Domains (5) summary

cd10482
Location:30 → 203

EphR_LBD_A4; Ligand Binding Domain of Ephrin type-A Receptor 4

cd00063
Location:441 → 532

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05066
Location:616 → 882

PTKc_EphR_A; Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors

pfam14575
Location:562 → 618

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain

cl15755
Location:911 → 949

SAM_superfamily; SAM (Sterile alpha motif )
NM_004438.5 → NP_004429.1 ephrin type-A receptor 4 isoform a precursor

See identical proteins and their annotated locations for NP_004429.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 both encode the same isoform (a).

Source sequence(s)

AC010899, BC105000, BM676153, DA451606

Consensus CDS

CCDS2447.1

UniProtKB/Swiss-Prot

P54764

UniProtKB/TrEMBL

A0A024R452

Related

ENSP00000281821.2, ENST00000281821.7

Conserved Domains (5) summary

cd09545
Location:911 → 981

SAM_EPH-A4; SAM domain of EPH-A4 subfamily of tyrosine kinase receptors

cd10482
Location:30 → 203

EphR_LBD_A4; Ligand Binding Domain of Ephrin type-A Receptor 4

cd00063
Location:441 → 532

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd05066
Location:616 → 882

PTKc_EphR_A; Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors

pfam14575
Location:562 → 618

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain