EPHA3 EPH receptor A3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EPHA3provided by HGNC
Official Full Name: EPH receptor A3provided by HGNC
Primary source: HGNC:HGNC:3387
See related: Ensembl:ENSG00000044524 MIM:179611; AllianceGenome:HGNC:3387
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: EK4; ETK; HEK; ETK1; HEK4; TYRO4
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. This gene encodes a protein that binds ephrin-A ligands. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Jul 2008]
Expression: Broad expression in prostate (RPKM 12.7), gall bladder (RPKM 11.9) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p11.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (89107621..89482134)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (89183660..89558507)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (89156771..89531284)

Chromosome 3 - NC_000003.12 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?

The Ephrin tyrosine kinase a3 (EphA3) is a novel mediator of RAGE-prompted motility of breast cancer cells.
Title: The Ephrin tyrosine kinase a3 (EphA3) is a novel mediator of RAGE-prompted motility of breast cancer cells.
Intranasal Delivery of Temozolomide-Conjugated Gold Nanoparticles Functionalized with Anti-EphA3 for Glioblastoma Targeting.
Title: Intranasal Delivery of Temozolomide-Conjugated Gold Nanoparticles Functionalized with Anti-EphA3 for Glioblastoma Targeting.
EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer.
Title: EPHA3 Contributes to Epigenetic Suppression of PTEN in Radioresistant Head and Neck Cancer.
Critical role of EphA3 in cancer and current state of EphA3 drug therapeutics.
Title: Critical role of EphA3 in cancer and current state of EphA3 drug therapeutics.
Sam68 Promotes the Progression of Human Breast Cancer through inducing Activation of EphA3.
Title: Sam68 Promotes the Progression of Human Breast Cancer through inducing Activation of EphA3.
EphA3 promotes the proliferation of NPC cells through negatively regulating the ability of FOG2.
Title: EphA3 promotes the proliferation of NPC cells through negatively regulating the ability of FOG2.
Increased EphA3 expression is an independent prognostic factor for a poor outcome and decreased survival in prostate cancer patients treated with radical prostatectomy.EphA3 expression in the prostate cancer was correlated with the pathological stage, bladder and rectal invasion, distant metastasis.
Title: The prognosis value of EphA3 and the androgen receptor in prostate cancer treated with radical prostatectomy.
Hypermethylation of a CpG island within the EPHA3 promoter provides a possible mechanism for loss of EphA3 expression and was associated with lymph node metastasis and TNM stage in colorectal cancer.
Title: EphA3 Downregulation by Hypermethylation Associated with Lymph Node Metastasis and TNM Stage in Colorectal Cancer.
EphA3 is a target of miR-340, and ectopic expression of EphA3 can promote the migration and invasion of cervical cancer cells, whereas restoration of EphA3 in miR-340-overexpressing cervical cancer cells reversed the suppressive effects of miR-340.
Title: MiR-340 suppresses the metastasis by targeting EphA3 in cervical cancer.
EphA3 mediated the tumor invasiveness and migration in radioresistant head and neck cancer cell lines and epithelial mesenchymal transition- related protein expression. Inhibition of EphA3 enhanced radiosensitivity in the AMC HN 3R cell line in vitro and in vivo study.
Title: EphA3 maintains radioresistance in head and neck cancers through epithelial mesenchymal transition.

Submit: New GeneRIF Correction See all GeneRIFs (49)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of chronic periodontitis in a general German population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analyses of nonsyndromic cleft lip with or without cleft palate identify six new risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

RH93446 (e-PCR)
- UniSTS:90882

SHGC-79129 (e-PCR)
- UniSTS:100895

D3S1101 (e-PCR)
- UniSTS:146837

RH121633 (e-PCR)
- UniSTS:134315

RH123819 (e-PCR)
- UniSTS:136140

D3S2366 (e-PCR)
- UniSTS:61653

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables GPI-linked ephrin receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables boss receptor activity	IEA Inferred from Electronic Annotation more info
enables brain-derived neurotrophic factor receptor activity	IEA Inferred from Electronic Annotation more info
enables ephrin receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables epidermal growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables fibroblast growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables hepatocyte growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables insulin receptor activity	IEA Inferred from Electronic Annotation more info
enables insulin-like growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables macrophage colony-stimulating factor receptor activity	IEA Inferred from Electronic Annotation more info
enables placental growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables platelet-derived growth factor alpha-receptor activity	IEA Inferred from Electronic Annotation more info
enables platelet-derived growth factor beta-receptor activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase collagen receptor activity	IEA Inferred from Electronic Annotation more info
enables stem cell factor receptor activity	IEA Inferred from Electronic Annotation more info
enables transmembrane-ephrin receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables vascular endothelial growth factor receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Kit signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in brain-derived neurotrophic factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in cell migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to retinoic acid	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in collagen-activated tyrosine kinase receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in ephrin receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in ephrin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in epidermal growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
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 fibroblast growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in hepatocyte growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in insulin-like growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in macrophage colony-stimulating factor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of endocytosis	IDA Inferred from Direct Assay more info
involved_in peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info
involved_in platelet-derived growth factor receptor-alpha signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in platelet-derived growth factor receptor-beta signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron projection development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein localization to plasma membrane	IDA Inferred from Direct Assay more info
involved_in regulation of GTPase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of actin cytoskeleton organization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of epithelial to mesenchymal transition	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of focal adhesion assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of microtubule cytoskeleton organization	IDA Inferred from Direct Assay more info	PubMed
involved_in vascular endothelial growth factor receptor-1 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in vascular endothelial growth factor signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in actin cytoskeleton	IDA Inferred from Direct Assay more info
located_in cytosol	IDA Inferred from Direct Assay more info
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in nuclear membrane	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: ephrin type-A receptor 3

Names: EPH-like kinase 4; TYRO4 protein tyrosine kinase; eph-like tyrosine kinase 1; human embryo kinase 1; testicular tissue protein Li 64; tyrosine-protein kinase receptor ETK1

NP_001397707.1

EC 2.7.10.1

NP_005224.2

EC 2.7.10.1

NP_872585.1

EC 2.7.10.1

XP_005264772.1

EC 2.7.10.1

XP_047303629.1

EC 2.7.10.1

XP_054201630.1

EC 2.7.10.1

XP_054201631.1

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.

Genomic

NG_023239.2 RefSeqGene

Range

5098..379611

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001410778.1 → NP_001397707.1 ephrin type-A receptor 3 isoform c precursor

Status: REVIEWED

Source sequence(s)

AC107028, AC109129, AC138973

Consensus CDS

CCDS93324.1

UniProtKB/TrEMBL

C9JXA2

Related

ENSP00000419190.1, ENST00000494014.1
NM_005233.6 → NP_005224.2 ephrin type-A receptor 3 isoform a precursor

See identical proteins and their annotated locations for NP_005224.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (a).

Source sequence(s)

AF213459, BC063282

Consensus CDS

CCDS2922.1

UniProtKB/Swiss-Prot

P29320, Q9H2V3, Q9H2V4

UniProtKB/TrEMBL

A0A140VJJ0, A8K5U6, Q6P4R6

Related

ENSP00000337451.2, ENST00000336596.7

Conserved Domains (8) summary

smart00454
Location:908 → 975

SAM; Sterile alpha motif

cd10481
Location:29 → 201

EphR_LBD_A3; Ligand Binding Domain of Ephrin type-A Receptor 3

cd00063
Location:437 → 528

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

pfam00041
Location:327 → 417

fn3; Fibronectin type III domain

pfam07714
Location:621 → 878

Pkinase_Tyr; Protein tyrosine kinase

pfam14575
Location:555 → 616

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain

cl15755
Location:912 → 974

SAM_superfamily; SAM (Sterile alpha motif )
NM_182644.3 → NP_872585.1 ephrin type-A receptor 3 isoform b precursor

See identical proteins and their annotated locations for NP_872585.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, compared to variant 1, that results in missing several 3' exons. It encodes isoform b which has a shorter and distinct C-terminus compared to isoform a. This isoform lacks a transmembrane domain and may be a secreted form of the Epha3 receptor.

Source sequence(s)

AC109129, AF213459

Consensus CDS

CCDS46875.1

UniProtKB/Swiss-Prot

P29320

Related

ENSP00000399926.2, ENST00000452448.6

Conserved Domains (4) summary

cd10481
Location:29 → 201

EphR_LBD_A3; Ligand Binding Domain of Ephrin type-A Receptor 3

cd00063
Location:437 → 528

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 ...

pfam00041
Location:327 → 417

fn3; Fibronectin type III domain

pfam07699
Location:269 → 304

GCC2_GCC3; GCC2 and GCC3

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

89107621..89482134

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005264715.4 → XP_005264772.1 ephrin type-A receptor 3 isoform X1

UniProtKB/TrEMBL

A8K5U6, Q6P4R6

Conserved Domains (8) summary

smart00454
Location:907 → 974

SAM; Sterile alpha motif

cd10481
Location:29 → 201

EphR_LBD_A3; Ligand Binding Domain of Ephrin type-A Receptor 3

cd00063
Location:437 → 527

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:615 → 881

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

pfam00041
Location:327 → 417

fn3; Fibronectin type III domain

pfam07714
Location:620 → 877

Pkinase_Tyr; Protein tyrosine kinase

pfam14575
Location:554 → 615

EphA2_TM; Ephrin type-A receptor 2 transmembrane domain

cl15755
Location:911 → 973

SAM_superfamily; SAM (Sterile alpha motif )
XM_047447673.1 → XP_047303629.1 ephrin type-A receptor 3 isoform X2