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EPHA4 EPH receptor A4 [ Homo sapiens (human) ]

Gene ID: 2043, updated on 6-Jan-2019

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

Genomic context

See EPHA4 in Genome Data Viewer
Location:
2q36.1
Exon count:
19
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 2 NC_000002.12 (221418027..221574202, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (222282747..222437010, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373896 Neighboring gene uncharacterized LOC107985989 Neighboring gene uncharacterized LOC107985988 Neighboring gene uncharacterized LOC107985990 Neighboring gene transmembrane protein 256 pseudogene 2 Neighboring gene uncharacterized LOC105373897 Neighboring gene uncharacterized LOC105373899 Neighboring gene ribosomal protein L23 pseudogene 5 Neighboring gene uncharacterized LOC105373898

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy.
NHGRI GWA Catalog
Genome-wide SNP associations with rubella-specific cytokine responses in measles-mumps-rubella vaccine recipients.
NHGRI GWA Catalog

Pathways from BioSystems

  • Axon guidance, organism-specific biosystem (from KEGG)
    Axon guidance, organism-specific biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
  • Axon guidance, conserved biosystem (from KEGG)
    Axon guidance, conserved biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
  • Axon guidance, organism-specific biosystem (from REACTOME)
    Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
  • Developmental Biology, organism-specific biosystem (from REACTOME)
    Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
  • EPH-Ephrin signaling, organism-specific biosystem (from REACTOME)
    EPH-Ephrin signaling, organism-specific biosystemDuring the development process cell migration and adhesion are the main forces involved in morphing the cells into critical anatomical structures. The ability of a cell to migrate to its correct dest...
  • EPH-ephrin mediated repulsion of cells, organism-specific biosystem (from REACTOME)
    EPH-ephrin mediated repulsion of cells, organism-specific biosystemDespite high-affinity multimeric interaction between EPHs and ephrins (EFNs), the cellular response to EPH-EFN engagement is usually repulsion between the two cells and signal termination. These repu...
  • EPHA forward signaling, organism-specific biosystem (from Pathway Interaction Database)
    EPHA forward signaling, organism-specific biosystem
    EPHA forward signaling
  • EPHA-mediated growth cone collapse, organism-specific biosystem (from REACTOME)
    EPHA-mediated growth cone collapse, organism-specific biosystemEPH/Ephrin signaling is coupled to Rho family GTPases such as Rac, Rho and Cdc42 that connect bidirectional receptor-ligand interactions to changes in the actin cytoskeleton (Noren & Pasquale 2004, G...
  • EphrinA-EPHA pathway, organism-specific biosystem (from Pathway Interaction Database)
    EphrinA-EPHA pathway, organism-specific biosystem
    EphrinA-EPHA pathway
  • Gene regulatory network modelling somitogenesis, organism-specific biosystem (from WikiPathways)
    Gene regulatory network modelling somitogenesis, organism-specific biosystemReaction scheme of the proposed gene regulatory network (GRN). The scheme details the full GRN for one cell and part of a neighboring cell for those reactions that involve ligand-receptor interactio...
  • Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
    Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
DH domain binding IDA
Inferred from Direct Assay
more info
PubMed 
GPI-linked ephrin receptor activity ISS
Inferred from Sequence or Structural Similarity
more info
 
PH domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
amyloid-beta binding TAS
Traceable Author Statement
more info
PubMed 
ephrin receptor binding IEA
Inferred from Electronic Annotation
more info
 
identical protein binding IEA
Inferred from Electronic Annotation
more info
 
kinase activity IGI
Inferred from Genetic Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein tyrosine kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
transmembrane receptor protein tyrosine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transmembrane-ephrin receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transmembrane-ephrin receptor activity ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
adult walking behavior IEA
Inferred from Electronic Annotation
more info
 
axon guidance IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cell adhesion IEA
Inferred from Electronic Annotation
more info
 
cellular response to amyloid-beta ISS
Inferred from Sequence or Structural Similarity
more info
 
corticospinal tract morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
ephrin receptor signaling pathway IGI
Inferred from Genetic Interaction
more info
PubMed 
ephrin receptor signaling pathway TAS
Traceable Author Statement
more info
 
fasciculation of motor neuron axon ISS
Inferred from Sequence or Structural Similarity
more info
 
fasciculation of sensory neuron axon ISS
Inferred from Sequence or Structural Similarity
more info
 
glial cell migration IEA
Inferred from Electronic Annotation
more info
 
motor neuron axon guidance ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of axon regeneration ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of long-term synaptic potentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of neuron projection development ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of proteolysis involved in cellular protein catabolic process IGI
Inferred from Genetic Interaction
more info
PubMed 
nephric duct morphogenesis IEA
Inferred from Electronic Annotation
more info
 
neuron projection fasciculation ISS
Inferred from Sequence or Structural Similarity
more info
 
neuron projection guidance ISS
Inferred from Sequence or Structural Similarity
more info
 
peptidyl-tyrosine phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of JUN kinase activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of Rho guanyl-nucleotide exchange factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of amyloid-beta formation IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of dendrite morphogenesis IEA
Inferred from Electronic Annotation
more info
 
positive regulation of protein tyrosine kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
protein autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
protein stabilization IGI
Inferred from Genetic Interaction
more info
PubMed 
regulation of GTPase activity ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of astrocyte differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of axonogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of dendritic spine morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of modification of synaptic structure ISS
Inferred from Sequence or Structural Similarity
more info
 
synapse pruning IEA
Inferred from Electronic Annotation
more info
 
transmembrane receptor protein tyrosine kinase signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Component Evidence Code Pubs
Golgi apparatus IEA
Inferred from Electronic Annotation
more info
 
Schaffer collateral - CA1 synapse IEA
Inferred from Electronic Annotation
more info
 
axon ISS
Inferred from Sequence or Structural Similarity
more info
 
axon terminus IEA
Inferred from Electronic Annotation
more info
 
axonal growth cone IEA
Inferred from Electronic Annotation
more info
 
cell junction IEA
Inferred from Electronic Annotation
more info
 
cell surface IEA
Inferred from Electronic Annotation
more info
 
cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 
dendrite ISS
Inferred from Sequence or Structural Similarity
more info
 
dendritic shaft ISS
Inferred from Sequence or Structural Similarity
more info
 
dendritic spine IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
dendritic spine ISS
Inferred from Sequence or Structural Similarity
more info
 
early endosome membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
 
filopodium IEA
Inferred from Electronic Annotation
more info
 
glutamatergic synapse IEA
Inferred from Electronic Annotation
more info
 
integral component of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
integral component of plasma membrane ISS
Inferred from Sequence or Structural Similarity
more info
 
integral component of postsynaptic membrane IEA
Inferred from Electronic Annotation
more info
 
integral component of presynaptic membrane IEA
Inferred from Electronic Annotation
more info
 
mitochondrial outer membrane IEA
Inferred from Electronic Annotation
more info
 
neuromuscular junction IEA
Inferred from Electronic Annotation
more info
 
neuron projection IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
perikaryon IEA
Inferred from Electronic Annotation
more info
 
plasma membrane NAS
Non-traceable Author Statement
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
postsynaptic density IEA
Inferred from Electronic Annotation
more info
 
receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 

General protein information

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
NP_001291466.1
NP_004429.1
XP_005246431.1

NCBI Reference Sequences (RefSeq)

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)

  1. NM_001304536.1NP_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:911981
    SAM_EPH-A4; SAM domain of EPH-A4 subfamily of tyrosine kinase receptors
    cd10482
    Location:30203
    EphR_LBD_A4; Ligand Binding Domain of Ephrin type-A Receptor 4
    cd00063
    Location:441532
    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:616882
    PTKc_EphR_A; Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors
    pfam14575
    Location:562616
    EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
  2. NM_001304537.1NP_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:860930
    SAM_EPH-A4; SAM domain of EPH-A4 subfamily of tyrosine kinase receptors
    smart00454
    Location:864924
    SAM; Sterile alpha motif
    cd10473
    Location:3152
    EphR_LBD_A; Ligand Binding Domain of Ephrin type-A Receptors
    cd00063
    Location:390481
    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:565831
    PTKc_EphR_A; Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors
    pfam07714
    Location:570827
    Pkinase_Tyr; Protein tyrosine kinase
    pfam14575
    Location:511565
    EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
  3. NM_001363748.1NP_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
    Conserved Domains (5) summary
    cd10482
    Location:30203
    EphR_LBD_A4; Ligand Binding Domain of Ephrin type-A Receptor 4
    cd00063
    Location:441532
    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:616882
    PTKc_EphR_A; Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors
    pfam14575
    Location:562616
    EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
    cl15755
    Location:911949
    SAM_superfamily; SAM (Sterile alpha motif )
  4. NM_004438.5NP_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, ENST00000281821.6
    Conserved Domains (5) summary
    cd09545
    Location:911981
    SAM_EPH-A4; SAM domain of EPH-A4 subfamily of tyrosine kinase receptors
    cd10482
    Location:30203
    EphR_LBD_A4; Ligand Binding Domain of Ephrin type-A Receptor 4
    cd00063
    Location:441532
    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:616882
    PTKc_EphR_A; Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors
    pfam14575
    Location:562616
    EphA2_TM; Ephrin type-A receptor 2 transmembrane domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p12 Primary Assembly

    Range
    221418027..221574202 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005246374.3XP_005246431.1  ephrin type-A receptor 4 isoform X1

    UniProtKB/TrEMBL
    E9PG71
    Related
    ENSP00000386276.1, ENST00000409854.5
    Conserved Domains (5) summary
    cd10482
    Location:30203
    EphR_LBD_A4; Ligand Binding Domain of Ephrin type-A Receptor 4
    cd00063
    Location:441532
    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:616882
    PTKc_EphR_A; Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors
    pfam14575
    Location:562616
    EphA2_TM; Ephrin type-A receptor 2 transmembrane domain
    cl15755
    Location:911949
    SAM_superfamily; SAM (Sterile alpha motif )
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