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.
| 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.
|
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?
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
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.
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.
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