Details for: EPHA1

Gene ID: 2041

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: EPHA1

Ensembl ID: ENSG00000146904

Description: EPH receptor A1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • secretory cell CL0000151
    CSI 4.79
    rCSI 5%
    PRS 99.83
  • intestinal epithelial cell CL0002563
    CSI 3.32
    rCSI 3.47%
    PRS 99.73

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [EPHA1](/details-gene/2041) is a protein-coding gene located on chromosome 7 that encodes the Ephrin type-A receptor 1, a member of the Eph receptor tyrosine kinase family. As a transmembrane receptor, [EPHA1](/details-gene/2041) plays a crucial role in mediating cell-cell signaling events that are fundamental to various biological processes. Its functions include regulating axon guidance, angiogenesis, and cell migration, adhesion, and proliferation. **Overall**, expression data highlights its significant role in epithelial tissues, showing the highest significance in `[secretory cells](/details-cell/CL0000151)` and `[intestinal epithelial cells](/details-cell/CL0002563)`, suggesting a primary function in maintaining tissue architecture and mediating cellular responses in these contexts. Clinically, it is associated with OMIM entry `[179610](https://omim.org/entry/179610)`. ## Cellular Roles and Expression Landscape The expression profile of [EPHA1](/details-gene/2041) points to a specialized role within epithelial tissues. **Overall**, the gene demonstrates its highest significance in `[secretory cells](/details-cell/CL0000151)` (CSI: 4.79) and `[intestinal epithelial cells](/details-cell/CL0002563)` (CSI: 3.32). This strong epithelial signature suggests that [EPHA1](/details-gene/2041) is involved in fundamental processes such as maintaining barrier integrity, regulating cell differentiation, and mediating cell-matrix interactions within these tissues. Its known role in regulating cell morphology and motility through interaction with integrin-linked kinase is consistent with a function in dynamic epithelial environments [Link](https://doi.org/10.1242/jcs.036467). While the provided data emphasizes its epithelial role, research also indicates functions in the immune system. For instance, its ligand, Ephrin-A1, has been shown to stimulate the migration of CD8+CCR7+ T lymphocytes, suggesting a potential role for [EPHA1](/details-gene/2041) in modulating immune cell trafficking [Link](https://doi.org/10.1002/eji.200737111). Furthermore, aberrant expression or activity of [EPHA1](/details-gene/2041) has been implicated in pathological conditions, including hepatocellular carcinoma, where it promotes angiogenesis and tumor growth [Link](https://pubmed.ncbi.nlm.nih.gov/20043122/). ## Pathways and Molecular Function Functionally, [EPHA1](/details-gene/2041) operates as a transmembrane receptor with protein tyrosine kinase activity. Its engagement with ephrin ligands initiates intracellular signaling cascades that regulate cytoskeletal organization and gene expression. Key molecular functions annotated for [EPHA1](/details-gene/2041) include `[ATP binding](/details-gene/GO:0005524)`, `[protein kinase activity](/details-gene/GO:0004672)`, and `[transmembrane-ephrin receptor activity](/details-gene/GO:0005005)`. The biological processes involving [EPHA1](/details-gene/2041) are diverse, reflecting its role as a master regulator of cell behavior. It is a central component of the `[ephrin receptor signaling pathway](/details-gene/GO:0048013)`, which governs both attractive and repulsive cellular cues. This is evident in its involvement in Reactome pathways such as `[Axon guidance](https://reactome.org/content/detail/R-HSA-422475)` and `[Eph-ephrin mediated repulsion of cells](https://reactome.org/content/detail/R-HSA-3928665)`. Furthermore, its participation in processes like `[positive regulation of angiogenesis](/details-gene/GO:0045766)`, `[negative regulation of cell migration](/details-gene/GO:0030336)`, and `[positive regulation of cell-matrix adhesion](/details-gene/GO:0001954)` is consistent with its high significance in `[intestinal epithelial cells](/details-cell/CL0002563)`, where these processes are critical for tissue homeostasis and repair. The receptor's presence in the `[plasma membrane](/details-gene/GO:0005886)` as part of a `[receptor complex](/details-gene/GO:0043235)` facilitates its role in sensing and responding to the extracellular environment. ## Research Directions The established roles of [EPHA1](/details-gene/2041) in cell adhesion, migration, and angiogenesis, combined with its specific expression patterns and implication in cancer, provide fertile ground for further investigation. **Proposed Hypotheses:** 1. Given its high significance in `[intestinal epithelial cells](/details-cell/CL0002563)` and its function in cell-matrix adhesion, it is hypothesized that [EPHA1](/details-gene/2041) signaling is a critical regulator of intestinal epithelial barrier integrity, where its dysregulation could contribute to inflammatory bowel disease or increase susceptibility to infection. 2. Based on reports that silencing [EPHA1](/details-gene/2041) has anti-tumor effects in hepatocellular carcinoma [Link](https://pubmed.ncbi.nlm.nih.gov/20043122/), we hypothesize that ligand-independent, oncogenic signaling by [EPHA1](/details-gene/2041) may be a key driver in a subset of epithelial-derived cancers, promoting cell proliferation and survival. 3. Considering its described role in T cell migration [Link](https://doi.org/10.1002/eji.200737111), it is proposed that [EPHA1](/details-gene/2041) expressed on epithelial cells acts as a co-regulatory receptor that directly modulates immune surveillance by binding to ephrin ligands on patrolling lymphocytes. **Experimental Approach:** To test the first hypothesis regarding intestinal barrier function, a compelling approach would be to use human intestinal organoids. CRISPR-Cas9 could be employed to knock out [EPHA1](/details-gene/2041) in these 3D culture systems. The functional consequence of its loss would be assessed by measuring transepithelial electrical resistance (TEER) to quantify barrier integrity. Furthermore, immunofluorescence microscopy for key junctional proteins (e.g., E-cadherin, ZO-1) would reveal any structural deficits, while challenging the organoids with pro-inflammatory cytokines or pathogens would determine if loss of [EPHA1](/details-gene/2041) sensitizes the epithelium to damage. **Therapeutic Potential:** As a cell surface receptor tyrosine kinase, [EPHA1](/details-gene/2041) is a highly druggable target. Its documented role in promoting tumorigenesis in specific contexts, such as hepatocellular carcinoma, suggests that it is a promising candidate for targeted cancer therapy. The therapeutic strategy would focus on **inhibition**. This could be achieved using small molecule kinase inhibitors designed to block its ATP-binding site and prevent downstream signaling, or through biologics such as monoclonal antibodies that can block ligand binding or mediate antibody-dependent cell-mediated cytotoxicity. Its potential as a therapeutic target in rheumatoid arthritis also warrants further exploration [Link](https://doi.org/10.1186/ar2447).

Genular Protein ID: 1810464171

Symbol: EPHA1_HUMAN

Name: Ephrin type-A receptor 1

UniProtKB Accession Codes:

P21709 A1L3V3 B5A966 B5A967 Q15405

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 4 CORUM 1 CPTAC 1 CTD 1 ChEBI 7 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EC 2 EMBL 16 Ensembl 2 EvolutionaryTrace 1 GO 23 Gene3D 6 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 20 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 4 PDBsum 4 PIR 1 PIRSF 1 PRINTS 1 PRO 1 PROSITE 9 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 6 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 4 RefSeq 1 Rhea 3 SIGNOR 1 SMART 5 SMR 1 STRING 1 SUPFAM 5 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2825356

Title: A novel putative tyrosine kinase receptor encoded by the eph gene.

PubMed ID: 2825356

DOI: 10.1126/science.2825356

PubMed ID: 10369740

Title: Genomic structure of the EPHA1 receptor tyrosine kinase gene.

PubMed ID: 10369740

DOI: 10.1006/mcpr.1999.0228

PubMed ID: 18593464

Title: Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis.

PubMed ID: 18593464

DOI: 10.1186/ar2447

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 9267020

Title: Unified nomenclature for Eph family receptors and their ligands, the ephrins.

PubMed ID: 9267020

DOI: 10.1016/s0092-8674(00)80500-0

PubMed ID: 17634955

Title: Ephrin-A1 stimulates migration of CD8+CCR7+ T lymphocytes.

PubMed ID: 17634955

DOI: 10.1002/eji.200737111

PubMed ID: 19118217

Title: EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility.

PubMed ID: 19118217

DOI: 10.1242/jcs.036467

PubMed ID: 20043122

Title: EphA1 receptor silencing by small interfering RNA has antiangiogenic and antitumor efficacy in hepatocellular carcinoma.

PubMed ID: 20043122

PubMed ID: 20596523

Title: Development and validation of a method for profiling post-translational modification activities using protein microarrays.

PubMed ID: 20596523

DOI: 10.1371/journal.pone.0011332

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 18728013

Title: Spatial structure and pH-dependent conformational diversity of dimeric transmembrane domain of the receptor tyrosine kinase EphA1.

PubMed ID: 18728013

DOI: 10.1074/jbc.m803089200

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

PubMed ID: 19369195

Title: Large-scale proteomics analysis of the human kinome.

PubMed ID: 19369195

DOI: 10.1074/mcp.m800588-mcp200

Sequence Information:

  • Length: 976
  • Mass: 108127
  • Checksum: 91EFCA69FFE17826
  • Sequence:
    • MERRWPLGLG LVLLLCAPLP PGARAKEVTL MDTSKAQGEL GWLLDPPKDG WSEQQQILNG 
TPLYMYQDCP MQGRRDTDHW LRSNWIYRGE EASRVHVELQ FTVRDCKSFP GGAGPLGCKE 
TFNLLYMESD QDVGIQLRRP LFQKVTTVAA DQSFTIRDLV SGSVKLNVER CSLGRLTRRG 
LYLAFHNPGA CVALVSVRVF YQRCPETLNG LAQFPDTLPG PAGLVEVAGT CLPHARASPR 
PSGAPRMHCS PDGEWLVPVG RCHCEPGYEE GGSGEACVAC PSGSYRMDMD TPHCLTCPQQ 
STAESEGATI CTCESGHYRA PGEGPQVACT GPPSAPRNLS FSASGTQLSL RWEPPADTGG 
RQDVRYSVRC SQCQGTAQDG GPCQPCGVGV HFSPGARGLT TPAVHVNGLE PYANYTFNVE 
AQNGVSGLGS SGHASTSVSI SMGHAESLSG LSLRLVKKEP RQLELTWAGS RPRSPGANLT 
YELHVLNQDE ERYQMVLEPR VLLTELQPDT TYIVRVRMLT PLGPGPFSPD HEFRTSPPVS 
RGLTGGEIVA VIFGLLLGAA LLLGILVFRS RRAQRQRQQR QRDRATDVDR EDKLWLKPYV 
DLQAYEDPAQ GALDFTRELD PAWLMVDTVI GEGEFGEVYR GTLRLPSQDC KTVAIKTLKD 
TSPGGQWWNF LREATIMGQF SHPHILHLEG VVTKRKPIMI ITEFMENGAL DAFLREREDQ 
LVPGQLVAML QGIASGMNYL SNHNYVHRDL AARNILVNQN LCCKVSDFGL TRLLDDFDGT 
YETQGGKIPI RWTAPEAIAH RIFTTASDVW SFGIVMWEVL SFGDKPYGEM SNQEVMKSIE 
DGYRLPPPVD CPAPLYELMK NCWAYDRARR PHFQKLQAHL EQLLANPHSL RTIANFDPRM 
TLRLPSLSGS DGIPYRTVSE WLESIRMKRY ILHFHSAGLD TMECVLELTA EDLTQMGITL 
PGHQKRILCS IQGFKD