EPHA1

UniProt ID: P21709
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

EPHA1 encodes ephrin type-A receptor 1, a single-pass plasma-membrane receptor tyrosine kinase in the Eph receptor family. It binds membrane-bound ephrin ligands on adjacent cells and signals through ligand-dependent autophosphorylation and forward signaling, coupling cell-cell contact to regulation of adhesion, spreading, migration, RhoA/ROCK-linked morphology, and context-dependent angiogenic or tumor cell behaviors. EPHA1 contains an extracellular ephrin ligand-binding region, a single transmembrane segment, an intracellular tyrosine kinase domain, and a SAM domain.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004714 transmembrane receptor protein tyrosine kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0005886 plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0043235 signaling receptor complex
IBA
GO_REF:0000033
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as a core receptor-complex annotation. Eph signaling requires ligand-bound receptor complexes at opposed cell membranes, and Reactome describes EPHA/EFNA binding, dimerization, tetramerization, and autophosphorylation events.
GO:0004672 protein kinase activity
IEA
GO_REF:0000002
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0004713 protein tyrosine kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0004714 transmembrane receptor protein tyrosine kinase activity
IEA
GO_REF:0000003
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0005003 ephrin receptor activity
IEA
GO_REF:0000120
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0005005 transmembrane-ephrin receptor activity
IEA
GO_REF:0000117
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0005524 ATP binding
IEA
GO_REF:0000002
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0005886 plasma membrane
IEA
GO_REF:0000120
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
IEA
GO_REF:0000002
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0016020 membrane
IEA
GO_REF:0000002
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0030155 regulation of cell adhesion
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: This annotation describes a context-dependent downstream adhesion, migration, angiogenesis, or interaction output of EPHA1 signaling rather than the core receptor-kinase activity.
Reason: Keep as a biologically supported but context-dependent downstream output. EPHA1 activation regulates morphology, adhesion, and motility through ILK/RhoA/ROCK, while HCC and fibronectin studies support angiogenesis and fibronectin-related phenotypes. These outputs are important but secondary to the defining ephrin receptor tyrosine kinase activity.
GO:0048013 ephrin receptor signaling pathway
IEA
GO_REF:0000120
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0045766 positive regulation of angiogenesis
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: This annotation describes a context-dependent downstream adhesion, migration, angiogenesis, or interaction output of EPHA1 signaling rather than the core receptor-kinase activity.
Reason: Keep as non-core. Angiogenesis evidence comes from cancer/knockdown or fibronectin-ligand contexts (PMID:20043122, PMID:18308734), making it a relevant phenotype rather than the core molecular role.
GO:0051496 positive regulation of stress fiber assembly
IEA
GO_REF:0000107
MARK AS OVER ANNOTATED
Summary: Stress-fiber assembly is an indirect transferred downstream term for EPHA1.
Reason: Mark as over-annotated because the cached evidence for stress-fiber assembly is indirect/transfer-based, and the more directly supported EPHA1 biology is receptor tyrosine kinase signaling through ILK/RhoA/ROCK with effects on spreading and migration. Broader morphology/motility annotations capture the evidence better.
GO:0005003 ephrin receptor activity
IDA
PMID:12775584
EphA4-mediated Rho activation via Vsm-RhoGEF expressed speci...
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
IDA
PMID:19118217
EphA1 interacts with integrin-linked kinase and regulates ce...
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0001968 fibronectin binding
IDA
PMID:18308734
Fibronectin type I repeat is a nonactivating ligand for EphA...
KEEP AS NON CORE
Summary: This annotation describes a context-dependent downstream adhesion, migration, angiogenesis, or interaction output of EPHA1 signaling rather than the core receptor-kinase activity.
Reason: Keep as non-core. PMID:18308734 supports fibronectin binding as a nonactivating ligand interaction involved in angiogenesis, but canonical ephrin receptor/tyrosine kinase activity remains the defining molecular function of EPHA1.
GO:0045766 positive regulation of angiogenesis
ISS
PMID:18308734
Fibronectin type I repeat is a nonactivating ligand for EphA...
KEEP AS NON CORE
Summary: This annotation describes a context-dependent downstream adhesion, migration, angiogenesis, or interaction output of EPHA1 signaling rather than the core receptor-kinase activity.
Reason: Keep as non-core. Angiogenesis evidence comes from cancer/knockdown or fibronectin-ligand contexts (PMID:20043122, PMID:18308734), making it a relevant phenotype rather than the core molecular role.
GO:0005886 plasma membrane
IDA
PMID:16862074
Expression profile of Eph receptors and ephrin ligands in hu...
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-3928578
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-3928604
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-3928607
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-3928628
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-3928642
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-3928651
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-4093327
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-3928591
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-3928597
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-3928646
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-480509
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0051496 positive regulation of stress fiber assembly
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: Stress-fiber assembly is an indirect transferred downstream term for EPHA1.
Reason: Mark as over-annotated because the cached evidence for stress-fiber assembly is indirect/transfer-based, and the more directly supported EPHA1 biology is receptor tyrosine kinase signaling through ILK/RhoA/ROCK with effects on spreading and migration. Broader morphology/motility annotations capture the evidence better.
GO:0001954 positive regulation of cell-matrix adhesion
IDA
PMID:19118217
EphA1 interacts with integrin-linked kinase and regulates ce...
KEEP AS NON CORE
Summary: This annotation describes a context-dependent downstream adhesion, migration, angiogenesis, or interaction output of EPHA1 signaling rather than the core receptor-kinase activity.
Reason: Keep as a biologically supported but context-dependent downstream output. EPHA1 activation regulates morphology, adhesion, and motility through ILK/RhoA/ROCK, while HCC and fibronectin studies support angiogenesis and fibronectin-related phenotypes. These outputs are important but secondary to the defining ephrin receptor tyrosine kinase activity.
GO:0005005 transmembrane-ephrin receptor activity
IDA
PMID:19118217
EphA1 interacts with integrin-linked kinase and regulates ce...
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept as part of the core EPHA1 functional profile. UniProt, PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands, autophosphorylates, and mediates cell-surface receptor protein tyrosine kinase/ephrin receptor signaling.
GO:0005886 plasma membrane
IDA
PMID:19118217
EphA1 interacts with integrin-linked kinase and regulates ce...
ACCEPT
Summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds ephrin ligands and signals through ligand-dependent kinase activation/autophosphorylation.
Reason: Accept plasma-membrane localization because EPHA1 is a single-pass Eph receptor at the cell membrane; this is supported by UniProt and Reactome, and is consistent with the curated IDA/TAS plasma-membrane annotations. The PMID:16862074 cache is abstract-only, so that specific localization paper cannot be fully re-reviewed here.
GO:0019901 protein kinase binding
IPI
PMID:19118217
EphA1 interacts with integrin-linked kinase and regulates ce...
KEEP AS NON CORE
Summary: This annotation describes a context-dependent downstream adhesion, migration, angiogenesis, or interaction output of EPHA1 signaling rather than the core receptor-kinase activity.
Reason: Keep as non-core. PMID:19118217 reports interaction with the protein kinases ILK and PTK2/FAK1, but protein kinase binding is an interaction mechanism downstream of ligand-stimulated EPHA1 rather than the primary receptor activity.
GO:0030335 positive regulation of cell migration
IMP
PMID:20043122
EphA1 receptor silencing by small interfering RNA has antian...
KEEP AS NON CORE
Summary: This annotation describes a context-dependent downstream adhesion, migration, angiogenesis, or interaction output of EPHA1 signaling rather than the core receptor-kinase activity.
Reason: Keep as a biologically supported but context-dependent downstream output. EPHA1 activation regulates morphology, adhesion, and motility through ILK/RhoA/ROCK, while HCC and fibronectin studies support angiogenesis and fibronectin-related phenotypes. These outputs are important but secondary to the defining ephrin receptor tyrosine kinase activity.
GO:0030336 negative regulation of cell migration
IDA
PMID:19118217
EphA1 interacts with integrin-linked kinase and regulates ce...
KEEP AS NON CORE
Summary: This annotation describes a context-dependent downstream adhesion, migration, angiogenesis, or interaction output of EPHA1 signaling rather than the core receptor-kinase activity.
Reason: Keep as a biologically supported but context-dependent downstream output. EPHA1 activation regulates morphology, adhesion, and motility through ILK/RhoA/ROCK, while HCC and fibronectin studies support angiogenesis and fibronectin-related phenotypes. These outputs are important but secondary to the defining ephrin receptor tyrosine kinase activity.
GO:0034446 substrate adhesion-dependent cell spreading
IDA
PMID:19118217
EphA1 interacts with integrin-linked kinase and regulates ce...
KEEP AS NON CORE
Summary: This annotation describes a context-dependent downstream adhesion, migration, angiogenesis, or interaction output of EPHA1 signaling rather than the core receptor-kinase activity.
Reason: Keep as a biologically supported but context-dependent downstream output. EPHA1 activation regulates morphology, adhesion, and motility through ILK/RhoA/ROCK, while HCC and fibronectin studies support angiogenesis and fibronectin-related phenotypes. These outputs are important but secondary to the defining ephrin receptor tyrosine kinase activity.
GO:0045766 positive regulation of angiogenesis
IMP
PMID:20043122
EphA1 receptor silencing by small interfering RNA has antian...
KEEP AS NON CORE
Summary: This annotation describes a context-dependent downstream adhesion, migration, angiogenesis, or interaction output of EPHA1 signaling rather than the core receptor-kinase activity.
Reason: Keep as non-core. Angiogenesis evidence comes from cancer/knockdown or fibronectin-ligand contexts (PMID:20043122, PMID:18308734), making it a relevant phenotype rather than the core molecular role.

Core Functions

Ligand-dependent transmembrane ephrin receptor activity at the plasma membrane, where EPHA1 binds membrane-bound ephrin ligands on adjacent cells to initiate contact-dependent forward signaling.

Supporting Evidence:
  • Reactome:R-HSA-3928646
    Membrane bound EPHs bind to EFNs with high affinity and this results in the development of close contacts between the cells
  • PMID:19118217
    The Eph-ephrin receptor-ligand system is implicated in cell behavior and morphology

Receptor protein tyrosine kinase/autophosphorylation activity that couples ephrin-A1 stimulation to ILK, RhoA/ROCK, adhesion, spreading, and motility outputs.

Supporting Evidence:
  • Reactome:R-HSA-3928578
    Following ligand binding, EPH signaling is initiated through autophosphorylation
  • PMID:19118217
    activation of EphA1 kinase inhibits cell spreading and migration in a RhoA-ROCK-dependent manner
  • PMID:19118217
    a novel interaction between EphA1 and integrin-linked kinase (ILK)

References

Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on Enzyme Commission mapping
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
EphA4-mediated Rho activation via Vsm-RhoGEF expressed specifically in vascular smooth muscle cells.
Expression profile of Eph receptors and ephrin ligands in human skin and downregulation of EphA1 in nonmelanoma skin cancer.
Fibronectin type I repeat is a nonactivating ligand for EphA1 and inhibits ATF3-dependent angiogenesis.
EphA1 interacts with integrin-linked kinase and regulates cell morphology and motility.
EphA1 receptor silencing by small interfering RNA has antiangiogenic and antitumor efficacy in hepatocellular carcinoma.
Reactome:R-HSA-3928578
EPH receptors autophosphorylate
Reactome:R-HSA-3928591
EPH:EFN tetramers oligomerise
Reactome:R-HSA-3928597
EPH:EFN dimers tetramerise
Reactome:R-HSA-3928604
SFKs phosphorylate VAV2,3
Reactome:R-HSA-3928607
p-EPHs bind VAV2,3
Reactome:R-HSA-3928628
VAV exchanges GTP for GDP on RAC1, activating it
Reactome:R-HSA-3928642
TIAM1 exchanges GTP for GDP on RAC1, activating it
Reactome:R-HSA-3928646
EPHAs bind EFNAs
Reactome:R-HSA-3928651
NGEF exchanges GTP for GDP on RHOA
Reactome:R-HSA-4093327
EPHA binds TIAM1
Reactome:R-HSA-480509
Expression of EPHA1

Suggested Questions for Experts

Q: Which EPHA1 downstream outputs are conserved physiological functions versus cancer- or cell-line-specific phenotypes?

Q: Does EPHA1 have Alzheimer-relevant roles in brain vascular, epithelial/barrier, immune, or glial cell contexts, or is its disease association indirect?

Q: Should the PMID:12775584 annotation be rechecked against full text or source curation notes, since the cached abstract is EphA4-focused?

Suggested Experiments

Experiment: Stimulate endogenous EPHA1 with ephrin-A1 in epithelial, endothelial, and myeloid/glial models, then measure autophosphorylation, ILK/FAK recruitment, RhoA activity, stress-fiber morphology, adhesion, spreading, and migration.

Hypothesis: EPHA1 regulates adhesion and motility through ligand-dependent ILK/RhoA/ROCK signaling in a cell-type-specific manner.

Type: ligand-stimulation signaling assay

Experiment: Perturb EPHA1 in human iPSC-derived endothelial, pericyte, astrocyte, and microglial co-culture systems and assay barrier integrity, cell-cell repulsion/adhesion, inflammatory signaling, and amyloid-related stress responses.

Hypothesis: EPHA1 Alzheimer relevance depends on vascular or barrier-cell signaling rather than a neuron-intrinsic core function.

Type: disease-context functional assay

📚 Additional Documentation

Notes

(EPHA1-notes.md)

EPHA1 notes

Automated deep research was attempted with just deep-research-falcon human EPHA1 --fallback perplexity-lite, but the run timed out before producing a deep-research file. This review therefore uses cached GOA publications, the UniProt record, Reactome pathway records, and the PANTHER family fetch.

EPHA1 encodes ephrin type-A receptor 1, a single-pass plasma-membrane receptor tyrosine kinase. UniProt describes it as a receptor tyrosine kinase that binds membrane-bound ephrin-A ligands on adjacent cells and signals by contact-dependent forward signaling. The local PANTHER fetch places EPHA1 in PTHR46877:SF20 within the ephrin receptor tyrosine kinase family. Reactome records support the same family-level model: EPH signaling begins with ligand binding and autophosphorylation, and EPHA receptors bind EFNA ligands on closely opposed cell surfaces.

The strongest EPHA1-specific functional publication in the GOA cache is PMID:19118217, but only the abstract is cached. The abstract states that "activation of EphA1 kinase inhibits cell spreading and migration in a RhoA-ROCK-dependent manner" and that EphA1 interacts with ILK [PMID:19118217 "activation of EphA1 kinase inhibits cell spreading and migration in a RhoA-ROCK-dependent manner"; PMID:19118217 "a novel interaction between EphA1 and integrin-linked kinase (ILK)"]. This supports the core receptor-kinase, signaling, adhesion/spreading, motility, and protein-kinase-binding annotations, but the unavailable full text limits detailed assessment of assay context.

PMID:18308734, also abstract-only, supports a fibronectin-binding activity and angiogenesis-related context. The abstract states that "binding of EphA1 to fibronectin through its type I repeat played an essential role in the angiogenesis" PMID:18308734. This is a credible non-ephrin ligand interaction, but it is not the main defining receptor-tyrosine-kinase activity.

PMID:20043122, abstract-only, supports HCC-context migration and angiogenesis phenotypes. The abstract reports that EphA1 knockdown decreased Huh-7 proliferation, motility, invasion, VEGF/MMP expression, tumor outgrowth, and microvessel density [PMID:20043122 "The knockdown resulted in decreased proliferation of Huh-7 cells, as well as decreased motility and invasion capability in vitro"; PMID:20043122 "microvessel density was found to be inhibited"]. These annotations should be kept as context-dependent non-core outputs rather than the core biochemical identity of EPHA1.

PMID:16862074 is abstract-only and supports EPHA1 expression in adult human skin and nonmelanoma skin cancer, but the abstract does not verify the plasma-membrane localization detail used in GOA PMID:16862074. Plasma-membrane localization is nevertheless well supported overall by UniProt and Reactome as a single-pass cell-membrane receptor.

PMID:12775584 is abstract-only and its title/abstract concern EphA4-mediated Rho activation, not EPHA1. Per curation guidance, this is not grounds to remove the EPHA1 ephrin-receptor annotation because EPHA1 receptor activity is independently well supported, but the reference should be flagged as unverified for direct EPHA1-specific support.

For curation, accept the core ephrin receptor, transmembrane receptor tyrosine kinase, ATP/protein-tyrosine-kinase, plasma-membrane, signaling receptor complex, and ephrin receptor signaling annotations. Keep context-dependent adhesion, migration, angiogenesis, fibronectin-binding, and kinase-binding annotations as non-core where they reflect downstream or cancer-context phenotypes. Mark the stress-fiber assembly transfers as over-annotated because available cached evidence is indirect and broader RhoA/ROCK morphology terms already capture the supported mechanism better.

2026-06-20 second-pass audit

The second-pass audit confirmed the existing EPHA1 review and manual reference metadata. No annotation action changes were needed: EPHA1 remains curated as a plasma-membrane ephrin receptor tyrosine kinase, with adhesion, migration, angiogenesis, fibronectin-binding, and stress-fiber outputs retained as non-core or over-annotated when they represent downstream or context-specific signaling rather than the primary receptor-kinase function.

📄 View Raw YAML

id: P21709
gene_symbol: EPHA1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'EPHA1 encodes ephrin type-A receptor 1, a single-pass plasma-membrane
  receptor tyrosine kinase in the Eph receptor family. It binds membrane-bound ephrin
  ligands on adjacent cells and signals through ligand-dependent autophosphorylation
  and forward signaling, coupling cell-cell contact to regulation of adhesion, spreading,
  migration, RhoA/ROCK-linked morphology, and context-dependent angiogenic or tumor
  cell behaviors. EPHA1 contains an extracellular ephrin ligand-binding region, a
  single transmembrane segment, an intracellular tyrosine kinase domain, and a SAM
  domain.'
alternative_products:
- name: '1'
  id: P21709-1
- name: '2'
  id: P21709-2
  sequence_note: VSP_056010, VSP_056013
- name: '3'
  id: P21709-3
  sequence_note: VSP_056011, VSP_056012
existing_annotations:
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0007169
    label: cell surface receptor protein tyrosine kinase signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0043235
    label: signaling receptor complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as a core receptor-complex annotation. Eph signaling requires
      ligand-bound receptor complexes at opposed cell membranes, and Reactome 
      describes EPHA/EFNA binding, dimerization, tetramerization, and 
      autophosphorylation events.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005003
    label: ephrin receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005005
    label: transmembrane-ephrin receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: enables
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0007169
    label: cell surface receptor protein tyrosine kinase signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0030155
    label: regulation of cell adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: This annotation describes a context-dependent downstream adhesion, 
      migration, angiogenesis, or interaction output of EPHA1 signaling rather 
      than the core receptor-kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Keep as a biologically supported but context-dependent downstream 
      output. EPHA1 activation regulates morphology, adhesion, and motility 
      through ILK/RhoA/ROCK, while HCC and fibronectin studies support 
      angiogenesis and fibronectin-related phenotypes. These outputs are 
      important but secondary to the defining ephrin receptor tyrosine kinase 
      activity.
- term:
    id: GO:0048013
    label: ephrin receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0045766
    label: positive regulation of angiogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: This annotation describes a context-dependent downstream adhesion, 
      migration, angiogenesis, or interaction output of EPHA1 signaling rather 
      than the core receptor-kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. Angiogenesis evidence comes from cancer/knockdown 
      or fibronectin-ligand contexts (PMID:20043122, PMID:18308734), making it a
      relevant phenotype rather than the core molecular role.
- term:
    id: GO:0051496
    label: positive regulation of stress fiber assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: Stress-fiber assembly is an indirect transferred downstream term 
      for EPHA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the cached evidence for stress-fiber 
      assembly is indirect/transfer-based, and the more directly supported EPHA1
      biology is receptor tyrosine kinase signaling through ILK/RhoA/ROCK with 
      effects on spreading and migration. Broader morphology/motility 
      annotations capture the evidence better.
- term:
    id: GO:0005003
    label: ephrin receptor activity
  evidence_type: IDA
  original_reference_id: PMID:12775584
  qualifier: enables
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
- term:
    id: GO:0007169
    label: cell surface receptor protein tyrosine kinase signaling pathway
  evidence_type: IDA
  original_reference_id: PMID:19118217
  qualifier: involved_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
- term:
    id: GO:0001968
    label: fibronectin binding
  evidence_type: IDA
  original_reference_id: PMID:18308734
  qualifier: enables
  review:
    summary: This annotation describes a context-dependent downstream adhesion, 
      migration, angiogenesis, or interaction output of EPHA1 signaling rather 
      than the core receptor-kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. PMID:18308734 supports fibronectin binding as a 
      nonactivating ligand interaction involved in angiogenesis, but canonical 
      ephrin receptor/tyrosine kinase activity remains the defining molecular 
      function of EPHA1.
- term:
    id: GO:0045766
    label: positive regulation of angiogenesis
  evidence_type: ISS
  original_reference_id: PMID:18308734
  qualifier: involved_in
  review:
    summary: This annotation describes a context-dependent downstream adhesion, 
      migration, angiogenesis, or interaction output of EPHA1 signaling rather 
      than the core receptor-kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. Angiogenesis evidence comes from cancer/knockdown 
      or fibronectin-ligand contexts (PMID:20043122, PMID:18308734), making it a
      relevant phenotype rather than the core molecular role.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:16862074
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3928578
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3928604
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3928607
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3928628
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3928642
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3928651
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4093327
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3928591
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3928597
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3928646
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-480509
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
    additional_reference_ids:
    - PMID:19118217
- term:
    id: GO:0051496
    label: positive regulation of stress fiber assembly
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: involved_in
  review:
    summary: Stress-fiber assembly is an indirect transferred downstream term 
      for EPHA1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Mark as over-annotated because the cached evidence for stress-fiber 
      assembly is indirect/transfer-based, and the more directly supported EPHA1
      biology is receptor tyrosine kinase signaling through ILK/RhoA/ROCK with 
      effects on spreading and migration. Broader morphology/motility 
      annotations capture the evidence better.
- term:
    id: GO:0001954
    label: positive regulation of cell-matrix adhesion
  evidence_type: IDA
  original_reference_id: PMID:19118217
  qualifier: involved_in
  review:
    summary: This annotation describes a context-dependent downstream adhesion, 
      migration, angiogenesis, or interaction output of EPHA1 signaling rather 
      than the core receptor-kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Keep as a biologically supported but context-dependent downstream 
      output. EPHA1 activation regulates morphology, adhesion, and motility 
      through ILK/RhoA/ROCK, while HCC and fibronectin studies support 
      angiogenesis and fibronectin-related phenotypes. These outputs are 
      important but secondary to the defining ephrin receptor tyrosine kinase 
      activity.
- term:
    id: GO:0005005
    label: transmembrane-ephrin receptor activity
  evidence_type: IDA
  original_reference_id: PMID:19118217
  qualifier: enables
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept as part of the core EPHA1 functional profile. UniProt, 
      PANTHER, Reactome, and EPHA1-specific abstracts support EPHA1 as a 
      single-pass plasma-membrane Eph receptor tyrosine kinase that binds ephrin
      ligands, autophosphorylates, and mediates cell-surface receptor protein 
      tyrosine kinase/ephrin receptor signaling.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:19118217
  qualifier: located_in
  review:
    summary: EPHA1 is a plasma-membrane Eph receptor tyrosine kinase that binds 
      ephrin ligands and signals through ligand-dependent kinase 
      activation/autophosphorylation.
    action: ACCEPT
    reason: Accept plasma-membrane localization because EPHA1 is a single-pass 
      Eph receptor at the cell membrane; this is supported by UniProt and 
      Reactome, and is consistent with the curated IDA/TAS plasma-membrane 
      annotations. The PMID:16862074 cache is abstract-only, so that specific 
      localization paper cannot be fully re-reviewed here.
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IPI
  original_reference_id: PMID:19118217
  qualifier: enables
  review:
    summary: This annotation describes a context-dependent downstream adhesion, 
      migration, angiogenesis, or interaction output of EPHA1 signaling rather 
      than the core receptor-kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. PMID:19118217 reports interaction with the protein
      kinases ILK and PTK2/FAK1, but protein kinase binding is an interaction 
      mechanism downstream of ligand-stimulated EPHA1 rather than the primary 
      receptor activity.
- term:
    id: GO:0030335
    label: positive regulation of cell migration
  evidence_type: IMP
  original_reference_id: PMID:20043122
  qualifier: involved_in
  review:
    summary: This annotation describes a context-dependent downstream adhesion, 
      migration, angiogenesis, or interaction output of EPHA1 signaling rather 
      than the core receptor-kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Keep as a biologically supported but context-dependent downstream 
      output. EPHA1 activation regulates morphology, adhesion, and motility 
      through ILK/RhoA/ROCK, while HCC and fibronectin studies support 
      angiogenesis and fibronectin-related phenotypes. These outputs are 
      important but secondary to the defining ephrin receptor tyrosine kinase 
      activity.
- term:
    id: GO:0030336
    label: negative regulation of cell migration
  evidence_type: IDA
  original_reference_id: PMID:19118217
  qualifier: involved_in
  review:
    summary: This annotation describes a context-dependent downstream adhesion, 
      migration, angiogenesis, or interaction output of EPHA1 signaling rather 
      than the core receptor-kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Keep as a biologically supported but context-dependent downstream 
      output. EPHA1 activation regulates morphology, adhesion, and motility 
      through ILK/RhoA/ROCK, while HCC and fibronectin studies support 
      angiogenesis and fibronectin-related phenotypes. These outputs are 
      important but secondary to the defining ephrin receptor tyrosine kinase 
      activity.
- term:
    id: GO:0034446
    label: substrate adhesion-dependent cell spreading
  evidence_type: IDA
  original_reference_id: PMID:19118217
  qualifier: involved_in
  review:
    summary: This annotation describes a context-dependent downstream adhesion, 
      migration, angiogenesis, or interaction output of EPHA1 signaling rather 
      than the core receptor-kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Keep as a biologically supported but context-dependent downstream 
      output. EPHA1 activation regulates morphology, adhesion, and motility 
      through ILK/RhoA/ROCK, while HCC and fibronectin studies support 
      angiogenesis and fibronectin-related phenotypes. These outputs are 
      important but secondary to the defining ephrin receptor tyrosine kinase 
      activity.
- term:
    id: GO:0045766
    label: positive regulation of angiogenesis
  evidence_type: IMP
  original_reference_id: PMID:20043122
  qualifier: involved_in
  review:
    summary: This annotation describes a context-dependent downstream adhesion, 
      migration, angiogenesis, or interaction output of EPHA1 signaling rather 
      than the core receptor-kinase activity.
    action: KEEP_AS_NON_CORE
    reason: Keep as non-core. Angiogenesis evidence comes from cancer/knockdown 
      or fibronectin-ligand contexts (PMID:20043122, PMID:18308734), making it a
      relevant phenotype rather than the core molecular role.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with 
    GO terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data
    to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning 
    models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:12775584
  title: EphA4-mediated Rho activation via Vsm-RhoGEF expressed specifically in 
    vascular smooth muscle cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: UNVERIFIED
    review_notes: Cached abstract/title focus on EphA4-mediated Rho activation, 
      not EPHA1. The EPHA1 receptor activity annotation is accepted based on 
      independent EPHA1 evidence, but this PMID is not verified as direct EPHA1 
      support from the available abstract.
- id: PMID:16862074
  title: Expression profile of Eph receptors and ephrin ligands in human skin 
    and downregulation of EphA1 in nonmelanoma skin cancer.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: UNVERIFIED
    review_notes: Cached abstract verifies EPHA1 expression in epidermis and 
      skin cancer context, but does not show the plasma-membrane localization 
      detail; full text is unavailable in cache.
- id: PMID:18308734
  title: Fibronectin type I repeat is a nonactivating ligand for EphA1 and 
    inhibits ATF3-dependent angiogenesis.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Cached abstract directly supports EphA1 binding to a 
      fibronectin type I repeat and an angiogenesis-related context.
- id: PMID:19118217
  title: EphA1 interacts with integrin-linked kinase and regulates cell 
    morphology and motility.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cached abstract directly supports EphA1 kinase activation, ILK
      interaction, and regulation of morphology, spreading, and motility.
- id: PMID:20043122
  title: EphA1 receptor silencing by small interfering RNA has antiangiogenic 
    and antitumor efficacy in hepatocellular carcinoma.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Cached abstract supports HCC knockdown effects on 
      proliferation, motility/invasion, VEGF/MMP expression, tumor outgrowth, 
      and microvessel density.
- id: Reactome:R-HSA-3928578
  title: EPH receptors autophosphorylate
  findings: []
- id: Reactome:R-HSA-3928591
  title: EPH:EFN tetramers oligomerise
  findings: []
- id: Reactome:R-HSA-3928597
  title: EPH:EFN dimers tetramerise
  findings: []
- id: Reactome:R-HSA-3928604
  title: SFKs phosphorylate VAV2,3
  findings: []
- id: Reactome:R-HSA-3928607
  title: p-EPHs bind VAV2,3
  findings: []
- id: Reactome:R-HSA-3928628
  title: VAV exchanges GTP for GDP on RAC1, activating it
  findings: []
- id: Reactome:R-HSA-3928642
  title: TIAM1 exchanges GTP for GDP on RAC1, activating it
  findings: []
- id: Reactome:R-HSA-3928646
  title: EPHAs bind EFNAs
  findings: []
- id: Reactome:R-HSA-3928651
  title: NGEF exchanges GTP for GDP on RHOA
  findings: []
- id: Reactome:R-HSA-4093327
  title: EPHA binds TIAM1
  findings: []
- id: Reactome:R-HSA-480509
  title: Expression of EPHA1
  findings: []
core_functions:
- description: Ligand-dependent transmembrane ephrin receptor activity at the 
    plasma membrane, where EPHA1 binds membrane-bound ephrin ligands on adjacent
    cells to initiate contact-dependent forward signaling.
  supported_by:
  - reference_id: Reactome:R-HSA-3928646
    supporting_text: Membrane bound EPHs bind to EFNs with high affinity and 
      this results in the development of close contacts between the cells
  - reference_id: PMID:19118217
    supporting_text: The Eph-ephrin receptor-ligand system is implicated in cell
      behavior and morphology
  molecular_function:
    id: GO:0005005
    label: transmembrane-ephrin receptor activity
  directly_involved_in:
  - id: GO:0048013
    label: ephrin receptor signaling pathway
  - id: GO:0007169
    label: cell surface receptor protein tyrosine kinase signaling pathway
  locations:
  - id: GO:0005886
    label: plasma membrane
  in_complex:
    id: GO:0043235
    label: receptor complex
- description: Receptor protein tyrosine kinase/autophosphorylation activity 
    that couples ephrin-A1 stimulation to ILK, RhoA/ROCK, adhesion, spreading, 
    and motility outputs.
  supported_by:
  - reference_id: Reactome:R-HSA-3928578
    supporting_text: Following ligand binding, EPH signaling is initiated 
      through autophosphorylation
  - reference_id: PMID:19118217
    supporting_text: activation of EphA1 kinase inhibits cell spreading and 
      migration in a RhoA-ROCK-dependent manner
  - reference_id: PMID:19118217
    supporting_text: a novel interaction between EphA1 and integrin-linked 
      kinase (ILK)
  molecular_function:
    id: GO:0004714
    label: transmembrane receptor protein tyrosine kinase activity
  directly_involved_in:
  - id: GO:0007169
    label: cell surface receptor protein tyrosine kinase signaling pathway
  locations:
  - id: GO:0005886
    label: plasma membrane
proposed_new_terms: []
suggested_questions:
- question: Which EPHA1 downstream outputs are conserved physiological functions
    versus cancer- or cell-line-specific phenotypes?
- question: Does EPHA1 have Alzheimer-relevant roles in brain vascular, 
    epithelial/barrier, immune, or glial cell contexts, or is its disease 
    association indirect?
- question: Should the PMID:12775584 annotation be rechecked against full text 
    or source curation notes, since the cached abstract is EphA4-focused?
suggested_experiments:
- hypothesis: EPHA1 regulates adhesion and motility through ligand-dependent 
    ILK/RhoA/ROCK signaling in a cell-type-specific manner.
  description: Stimulate endogenous EPHA1 with ephrin-A1 in epithelial, 
    endothelial, and myeloid/glial models, then measure autophosphorylation, 
    ILK/FAK recruitment, RhoA activity, stress-fiber morphology, adhesion, 
    spreading, and migration.
  experiment_type: ligand-stimulation signaling assay
- hypothesis: EPHA1 Alzheimer relevance depends on vascular or barrier-cell 
    signaling rather than a neuron-intrinsic core function.
  description: Perturb EPHA1 in human iPSC-derived endothelial, pericyte, 
    astrocyte, and microglial co-culture systems and assay barrier integrity, 
    cell-cell repulsion/adhesion, inflammatory signaling, and amyloid-related 
    stress responses.
  experiment_type: disease-context functional assay