atg1 encodes the Dictyostelium discoideum ortholog of the Atg1/ULK1 serine/threonine protein kinase, the most upstream component of the macroautophagy induction machinery. The protein has an N-terminal protein kinase domain (residues ~7-266) followed by an asparagine/glutamine-rich low-complexity region and a conserved C-terminal domain required for its localization to forming autophagosomes. Atg1 is the catalytic subunit of the Atg1 kinase complex (with Atg13 and Atg101), and its kinase activity initiates phagophore/autophagosome formation. Because Dictyostelium undergoes starvation-induced multicellular development that depends on autophagy for nutrient mobilization, Atg1 is essential for aggregation and for normal fruiting-body (sorocarp) formation, and it is required for the vacuolar (autophagic) cell death of terminally differentiating cells. Atg1-dependent autophagy also contributes to cell-autonomous defense against ingested bacteria and yeasts and to nutrient and energy homeostasis, and the kinase additionally influences macropinocytosis, cell size and nuclear division, gene expression, and mitochondrial energy balance. Atg1 localizes predominantly to the cytoplasm and cytosol, with a pool at the preautophagosomal structure (phagophore assembly site) membrane.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005737
cytoplasm
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Cytoplasmic localization is correct and directly supported by experimental evidence in Dictyostelium; Atg1-GFP shows a general cytoplasmic distribution.
Reason: Atg1 acts predominantly in the cytoplasm, consistent with direct localization data and with its role as the cytoplasmic autophagy-initiating kinase.
Supporting Evidence:
PMID:26246495
Atg1 fused to GFP has been shown previously to have a general cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
|
|
GO:0000045
autophagosome assembly
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Atg1 is the upstream kinase that initiates autophagosome formation, a core conserved function directly demonstrated in Dictyostelium.
Reason: Kinase-dead Atg1 blocks functional autophagosome formation and Atg1 is required for macroautophagy, making autophagosome assembly a core function.
Supporting Evidence:
PMID:17031001
In cells expressing dominant-negative DdAtg1, autophagosomes are formed and accumulate but seem not to be functional
|
|
GO:0000423
mitophagy
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: Mitophagy is a conserved ULK1/Atg1 selective-autophagy function, but direct evidence in Dictyostelium is lacking; the one study of Atg1 and mitochondria concluded an ancillary role in energy balance rather than direct organelle turnover.
Reason: The IBA transfer of mitophagy from ULK1 orthologs is plausible but not demonstrated for Dictyostelium Atg1, where mitochondrial effects appear indirect; retained as non-core pending direct evidence.
Supporting Evidence:
PMID:39056773
Atg1's effects on energy homeostasis indicate a peripheral ancillary role in the mitochondrial signalling network, with effects on energy balance rather than direct effects on electron transport chain function
|
|
GO:0010506
regulation of autophagy
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Atg1 is the induction-regulating kinase of the autophagy pathway, a core conserved function.
Reason: As the catalytic subunit of the Atg1 complex, Atg1 controls the induction of autophagy, consistent with this annotation.
Supporting Evidence:
PMID:26246495
The first steps of induction and nucleation are controlled by the serine/threonine kinase Atg1/ULK1 and the class III PI3 K VPS34
|
|
GO:0042594
response to starvation
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Atg1-dependent autophagy is induced by and required for survival during starvation, well supported in Dictyostelium.
Reason: atg1 mutants show reduced survival during nitrogen starvation, directly linking Atg1 to the starvation response.
Supporting Evidence:
PMID:14736886
reduced survival during nitrogen starvation
|
|
GO:0061709
reticulophagy
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: Reticulophagy (ER-phagy) is a conserved selective-autophagy branch inferred from orthologs, but has not been demonstrated for Dictyostelium Atg1.
Reason: No direct evidence for ER-selective autophagy by Dictyostelium Atg1; retained as a non-core phylogenetic inference.
|
|
GO:0000407
phagophore assembly site
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Atg1 acts at the phagophore assembly site (preautophagosomal structure), where it initiates autophagosome formation.
Reason: Kinase-dead Atg1 colocalizes with the Atg8 marker of preautophagosomal structures, supporting activity at this site.
Supporting Evidence:
PMID:17031001
colocalizes with red fluorescent protein (RFP)-tagged DdAtg8, a marker of
|
|
GO:0005776
autophagosome
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Atg1 localizes to preautophagosomal structures and autophagosomes as shown by colocalization with the Atg8 marker.
Reason: Direct colocalization of Atg1 with RFP-Atg8-labeled autophagosomes supports this localization annotation.
Supporting Evidence:
PMID:17031001
a marker of preautophagosomal structures and autophagosomes
|
|
GO:0004674
protein serine/threonine kinase activity
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Atg1 is a serine/threonine protein kinase; this is the core molecular function.
Reason: The conserved kinase domain and demonstrated kinase-dependent (dominant-negative kinase-dead) function establish Ser/Thr kinase activity as the core molecular function.
Supporting Evidence:
PMID:17031001
Kinase-negative DdAtg1 acts in a
|
|
GO:0034045
phagophore assembly site membrane
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Atg1 associates with the phagophore assembly site (preautophagosomal structure) membrane as a peripheral membrane protein.
Reason: Consistent with UniProt subcellular location (preautophagosomal structure membrane, peripheral) and with Atg1 activity at the PAS.
Supporting Evidence:
PMID:17031001
a marker of preautophagosomal structures and autophagosomes
|
|
GO:0005829
cytosol
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Consistent with the observed diffuse cytoplasmic/cytosolic distribution of Atg1.
Reason: Atg1-GFP shows a general cytoplasmic pattern, consistent with a cytosolic pool.
Supporting Evidence:
PMID:26246495
Atg1 fused to GFP has been shown previously to have a general cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
|
|
GO:0034727
piecemeal microautophagy of the nucleus
|
IBA
GO_REF:0000033 |
KEEP AS NON CORE |
Summary: A yeast-derived selective microautophagy process; not demonstrated for Dictyostelium Atg1.
Reason: No direct evidence in Dictyostelium; retained as a non-core phylogenetic inference from fungal orthologs.
|
|
GO:0004672
protein kinase activity
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: General protein kinase activity, a correct parent term of the specific Ser/Thr kinase activity.
Reason: Correct but less specific than protein serine/threonine kinase activity; the more specific term is captured elsewhere.
Supporting Evidence:
PMID:17031001
these domains are essential for autophagy and development
|
|
GO:0004674
protein serine/threonine kinase activity
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: Core molecular function, correctly assigned by automated methods.
Reason: Atg1 belongs to the APG1/unc-51/ULK1 Ser/Thr kinase subfamily; this is the core molecular function.
Supporting Evidence:
PMID:26246495
the serine/threonine kinase Atg1/ULK1
|
|
GO:0005524
ATP binding
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: ATP binding is required for kinase catalysis and is supported by the conserved ATP-binding motif in the kinase domain.
Reason: The protein has a canonical protein kinase ATP-binding site; ATP binding is intrinsic to its catalytic function.
Supporting Evidence:
PMID:26246495
the serine/threonine kinase Atg1/ULK1
|
|
GO:0005737
cytoplasm
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Cytoplasmic localization from UniProt subcellular location mapping; correct.
Reason: Consistent with direct experimental evidence for cytoplasmic localization.
Supporting Evidence:
PMID:26246495
Atg1 fused to GFP has been shown previously to have a general cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
|
|
GO:0034045
phagophore assembly site membrane
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: Preautophagosomal structure membrane localization from UniProt; consistent with Atg1 activity at the PAS.
Reason: Matches UniProt subcellular location (preautophagosomal structure membrane) and Atg1's role at the phagophore assembly site.
Supporting Evidence:
PMID:17031001
a marker of preautophagosomal structures and autophagosomes
|
|
GO:0106310
protein serine kinase activity
|
IEA
GO_REF:0000116 |
ACCEPT |
Summary: Serine kinase activity assigned via Rhea reaction mapping; consistent with the Ser/Thr kinase activity of Atg1.
Reason: Correct reflection of the phosphotransferase reaction catalyzed by this Ser/Thr kinase.
Supporting Evidence:
PMID:26246495
the serine/threonine kinase Atg1/ULK1
|
|
GO:0071692
protein localization to extracellular region
|
IMP
PMID:38986731 Trafficking of adhesion and aggregation-modulating proteins ... |
KEEP AS NON CORE |
Summary: atg1 (with atg9) modulates the intracellular and extracellular amounts of the adhesion protein CadA and the secreted counting factor CtnA during aggregation, an autophagy-dependent secretion role.
Reason: The effect on extracellular protein levels is a downstream consequence of Atg1-dependent autophagy and unconventional secretion, not a core molecular function; retained as a non-core process.
Supporting Evidence:
PMID:38986731
The intracellular and extracellular amounts of CadA are modulated by autophagy genes
|
|
GO:0005737
cytoplasm
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Cytoplasmic localization inferred from orthologs; consistent with direct Dictyostelium data.
Reason: Supported by direct experimental localization of Atg1 to the cytoplasm.
Supporting Evidence:
PMID:26246495
Atg1 fused to GFP has been shown previously to have a general cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
|
|
GO:0034045
phagophore assembly site membrane
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: PAS membrane localization inferred from orthologs; consistent with Atg1 activity at the phagophore assembly site.
Reason: Matches UniProt subcellular location and Atg1's autophagy-initiating role.
Supporting Evidence:
PMID:17031001
a marker of preautophagosomal structures and autophagosomes
|
|
GO:0106310
protein serine kinase activity
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Serine kinase activity inferred from sequence similarity; consistent with the core Ser/Thr kinase function.
Reason: Correct reflection of Atg1 kinase activity.
Supporting Evidence:
PMID:26246495
the serine/threonine kinase Atg1/ULK1
|
|
GO:0000902
cell morphogenesis
|
IMP
PMID:39056773 The Multifaceted Interactions of Dictyostelium Atg1 with Mit... |
KEEP AS NON CORE |
Summary: atg1 null cells are consistently smaller and show altered nuclear division; this reflects effects on cell size/division rather than a dedicated morphogenetic program.
Reason: The cell-size phenotype is a pleiotropic consequence of altered autophagy and growth/energy homeostasis, not a core function; retained as non-core.
Supporting Evidence:
PMID:39056773
the null mutant exhibited consistently smaller average cell sizes when grown axenically
|
|
GO:0009267
cellular response to starvation
|
IDA
PMID:39056773 The Multifaceted Interactions of Dictyostelium Atg1 with Mit... |
KEEP AS NON CORE |
Summary: Atg1 increases tolerance of Dictyostelium to starvation, consistent with its role in starvation-induced autophagy.
Reason: A genuine, experimentally supported role, but downstream of the core kinase/autophagy function; retained as non-core.
Supporting Evidence:
PMID:39056773
Atg1 increases the tolerance of D. discoideum to starvation and cAMP treatment
|
|
GO:0030587
sorocarp development
|
IDA
PMID:39056773 The Multifaceted Interactions of Dictyostelium Atg1 with Mit... |
KEEP AS NON CORE |
Summary: Altered atg1 expression produces smaller fruiting bodies and multi-tipped aggregates, confirming a role in multicellular (sorocarp) development.
Reason: A pleiotropic developmental role that follows from Atg1-dependent autophagy during starvation-induced development; retained as non-core.
Supporting Evidence:
PMID:39056773
both atg1 antisense inhibition and overexpression resulted in smaller fruiting bodies
|
|
GO:0048548
regulation of pinocytosis
|
IMP
PMID:39056773 The Multifaceted Interactions of Dictyostelium Atg1 with Mit... |
KEEP AS NON CORE |
Summary: Atg1 positively regulates macropinocytosis; the null mutant has a macropinocytic defect and uptake correlates with atg1 expression.
Reason: A real, experimentally supported regulatory effect on macropinocytic uptake, but a downstream/pleiotropic role rather than a core function.
Supporting Evidence:
PMID:39056773
the atg1 null mutant displayed a macropinocytic defect
|
|
GO:0010629
negative regulation of gene expression
|
IDA
PMID:39056773 The Multifaceted Interactions of Dictyostelium Atg1 with Mit... |
KEEP AS NON CORE |
Summary: Overexpression data suggest Atg1 negatively regulates the prestalk marker ecmA; the effect on individual genes was modest.
Reason: A downstream developmental gene-expression effect, supported but not a core molecular function; retained as non-core.
Supporting Evidence:
PMID:39056773
This suggests that Atg1 negatively regulates prestalk gene (ecmA) expression
|
|
GO:0009617
response to bacterium
|
IMP
PMID:22575510 Lipopolysaccharide induction of autophagy is associated with... |
KEEP AS NON CORE |
Summary: atg1 is required for LPS-enhanced clearance of phagocytosed bacteria, linking Atg1-dependent autophagy to the antibacterial response.
Reason: A genuine cell-autonomous defense role mediated by autophagy, but downstream of the core kinase/autophagy function; retained as non-core.
Supporting Evidence:
PMID:22575510
LPS pre-treatment did not enhance clearance of phagocytized S. aureus in cells deficient for either atg1 or atg9
|
|
GO:0031152
aggregation involved in sorocarp development
|
IMP
PMID:39056773 The Multifaceted Interactions of Dictyostelium Atg1 with Mit... |
KEEP AS NON CORE |
Summary: atg1-null cells are unable to aggregate, a hallmark of severe autophagy impairment in Dictyostelium development.
Reason: An experimentally established developmental phenotype downstream of Atg1-dependent autophagy; retained as non-core.
Supporting Evidence:
PMID:26246495
Amoebas in which Atg1 has been knocked out are unable to aggregate
|
|
GO:0043327
chemotaxis to cAMP
|
IMP
PMID:39056773 The Multifaceted Interactions of Dictyostelium Atg1 with Mit... |
UNDECIDED |
Summary: This study measured cAMP/starvation survival and aggregation timing but did not directly assay chemotaxis to cAMP; a direct chemotaxis role for Atg1 cannot be verified from the available text.
Reason: The cited paper does not present a direct chemotaxis assay, and antisense inhibition had no pronounced effect on aggregation; the supporting evidence for a specific chemotaxis-to-cAMP function cannot be verified.
|
|
GO:0043457
regulation of cellular respiration
|
IDA
PMID:39056773 The Multifaceted Interactions of Dictyostelium Atg1 with Mit... |
KEEP AS NON CORE |
Summary: Knockout of atg1 alters mitochondrial and non-mitochondrial respiration, supporting a role in modulating cellular respiration.
Reason: An experimentally supported but indirect/peripheral effect on energy homeostasis, not a core molecular function; retained as non-core.
Supporting Evidence:
PMID:39056773
knocking out atg1 caused reductions in basal mitochondrial and non-mitochondrial respiration
|
|
GO:0043653
mitochondrial fragmentation involved in apoptotic process
|
IDA
PMID:39056773 The Multifaceted Interactions of Dictyostelium Atg1 with Mit... |
UNDECIDED |
Summary: The cited study characterized mitochondrial membrane mass, potential, ROS and respiration but did not demonstrate mitochondrial fragmentation as part of an apoptotic process; Dictyostelium cell death is characteristically non-apoptotic.
Reason: The specific term (apoptotic mitochondrial fragmentation) is not supported by the available text and apoptosis is not an established Dictyostelium cell-death mode; the basis for this annotation cannot be verified.
|
|
GO:0044351
macropinocytosis
|
IDA
PMID:39056773 The Multifaceted Interactions of Dictyostelium Atg1 with Mit... |
KEEP AS NON CORE |
Summary: atg1-null cells display a macropinocytic defect and macropinocytic uptake correlates positively with atg1 expression.
Reason: A genuine effect on macropinocytosis, but a downstream/pleiotropic role rather than a core molecular function; retained as non-core.
Supporting Evidence:
PMID:39056773
macropinocytic uptake rates were positively correlated with the atg1 expression index
|
|
GO:0004672
protein kinase activity
|
IDA
PMID:17031001 Function of the Dictyostelium discoideum Atg1 kinase during ... |
ACCEPT |
Summary: Direct evidence that the Atg1 kinase domain is essential for function; kinase-dead Atg1 acts as a dominant negative.
Reason: The kinase domain is essential for autophagy and development, and a kinase-negative mutant is dominant-negative, directly demonstrating catalytic protein kinase function.
Supporting Evidence:
PMID:17031001
these domains are essential for autophagy and development
|
|
GO:0016236
macroautophagy
|
IMP
PMID:17031001 Function of the Dictyostelium discoideum Atg1 kinase during ... |
ACCEPT |
Summary: Atg1 kinase and its conserved C-terminal domain are essential for macroautophagy in Dictyostelium, a core function.
Reason: Kinase-dead Atg1 blocks functional autophagy and the domains are essential for autophagy; macroautophagy is a core biological process for Atg1.
Supporting Evidence:
PMID:17031001
In cells expressing dominant-negative DdAtg1, autophagosomes are formed and accumulate but seem not to be functional
|
|
GO:0048102
autophagic cell death
|
IMP
PMID:15358773 Autophagy gene disruption reveals a non-vacuolar cell death ... |
KEEP AS NON CORE |
Summary: atg1 disruption blocks autophagy and vacuolization in the developmental vacuolar cell death model, showing Atg1 is required for autophagic (vacuolar) cell death.
Reason: An experimentally supported developmental cell-death role that is downstream of Atg1-dependent autophagy; retained as non-core.
Supporting Evidence:
PMID:15358773
led in atg1 mutant cells to impaired autophagy and to no vacuolization
|
|
GO:0008047
enzyme activator activity
|
IDA
PMID:26246495 Dissecting the function of Atg1 complex in Dictyostelium aut... |
KEEP AS NON CORE |
Summary: Atg1 positively regulates the activity of the pentose-phosphate-pathway enzyme transketolase (TKT), with which it physically interacts; TKT activity rises with Atg1 overexpression and falls in atg1-null or kinase-dead conditions.
Reason: Atg1 acts as a positive regulator of TKT activity (likely via its kinase function), but this enzyme-activation role is a specialized regulatory link rather than the core evolved molecular function; retained as non-core.
Supporting Evidence:
PMID:26246495
There is an increase in activity in cells overexpressing Atg1. By contrast, TKT activity decreases in cells in which atg1 has been deleted
|
|
GO:0097300
programmed necrotic cell death
|
IDA
PMID:17150370 From autophagic to necrotic cell death in Dictyostelium. |
UNDECIDED |
Summary: This review describes that disrupting atg1 reveals a non-vacuolar (necrotic-like) cell death pathway; necrotic death occurs in the absence of Atg1 rather than requiring it, so a positive involvement of Atg1 in necrotic death is not clearly supported.
Reason: The relationship between Atg1 and necrotic cell death is indirect (necrosis is unmasked when autophagic death is blocked); the supporting text is from a review and does not establish that Atg1 is involved_in programmed necrotic death.
|
|
GO:0005515
protein binding
|
IPI
PMID:31680241 AMPKα promotes basal autophagy induction in Dictyostelium di... |
KEEP AS NON CORE |
Summary: Co-immunoprecipitation shows an AMPK-ATG1 interaction conserved in basal autophagy. Bare 'protein binding' is uninformative; the meaningful content is the specific interaction with AMPK.
Reason: Per curation guidance, generic protein binding is not retained as a core function; the AMPK interaction is captured here as a non-core regulatory partnership.
Supporting Evidence:
PMID:31680241
Co-immunoprecipitation studies show conservation of the AMPK-ATG1
|
|
GO:0050830
defense response to Gram-positive bacterium
|
IDA
PMID:28414774 Mycobacterium marinum antagonistically induces an autophagic... |
UNDECIDED |
Summary: This study focuses on the ESX-1/TORC1-dependent manipulation of autophagy by Mycobacterium marinum; a specific, verifiable role for Atg1 in defense against a Gram-positive bacterium is not evident from the available text.
Reason: The cached text does not establish an Atg1-specific defense role against Gram-positive bacteria; the annotation cannot be verified from the available evidence.
|
|
GO:1905037
autophagosome organization
|
IMP
PMID:28414774 Mycobacterium marinum antagonistically induces an autophagic... |
KEEP AS NON CORE |
Summary: Atg1 is required for autophagosome formation/organization, an essentially core autophagy function; autophagosomes formed without functional Atg1 are aberrant.
Reason: Autophagosome organization is closely tied to Atg1's core autophagy-initiating role; captured here as a non-core process-level annotation with the core function recorded under macroautophagy/autophagosome assembly.
Supporting Evidence:
PMID:17031001
In cells expressing dominant-negative DdAtg1, autophagosomes are formed and accumulate but seem not to be functional
|
|
GO:0005515
protein binding
|
IPI
PMID:26246495 Dissecting the function of Atg1 complex in Dictyostelium aut... |
KEEP AS NON CORE |
Summary: Yeast two-hybrid and pull-down show Atg1 interacts with Atg13 and with the pentose-phosphate enzyme transketolase (TKT). Bare 'protein binding' is uninformative; the specific partners are the meaningful content.
Reason: Per curation guidance, generic protein binding is not retained as core; the Atg13 and TKT interactions are better represented via the Atg1 complex membership and the enzyme-activator annotation.
Supporting Evidence:
PMID:26246495
TKT–HA is efficiently pulled down by GFP-Atg1
|
|
GO:1990316
Atg1/ULK1 kinase complex
|
IDA
PMID:26246495 Dissecting the function of Atg1 complex in Dictyostelium aut... |
ACCEPT |
Summary: Atg1 is the catalytic subunit of the conserved Atg1-Atg13-Atg101 kinase complex in Dictyostelium, confirmed by yeast two-hybrid and pull-down.
Reason: Direct evidence establishes the Atg1-Atg13-Atg101 core complex, making Atg1/ULK1 kinase complex membership a core annotation.
Supporting Evidence:
PMID:26246495
The core of this assembly of proteins is formed by Atg1-Atg13-Atg101, which seems to be conserved
|
|
GO:0001878
response to yeast
|
IMP
PMID:27818653 Dictyostelium discoideum as a Novel Host System to Study the... |
KEEP AS NON CORE |
Summary: atg1-null cells show altered (increased) ability to predate yeast, implicating Atg1-dependent autophagy in the amoeba's interaction with yeast.
Reason: A downstream, autophagy-mediated host-microbe interaction phenotype; retained as non-core.
Supporting Evidence:
PMID:27818653
mutants increase (atg1-, kil1-, kil2-) or decrease (atg6-) the ability of the
|
|
GO:0035891
exit from host cell
|
IMP
PMID:25646440 The autophagic machinery ensures nonlytic transmission of my... |
KEEP AS NON CORE |
Summary: The autophagic machinery is required for nonlytic cell-to-cell transmission (ejection) of mycobacteria; impairing autophagy blocks transmission.
Reason: A specialized host-pathogen role mediated by Atg1-dependent autophagy; retained as non-core.
Supporting Evidence:
PMID:25646440
If autophagy is impaired, cell-to-cell transmission is
|
|
GO:0042742
defense response to bacterium
|
IMP
PMID:25646440 The autophagic machinery ensures nonlytic transmission of my... |
KEEP AS NON CORE |
Summary: Atg1-dependent autophagy contributes to control of intracellular mycobacteria; autophagy impairment compromises the host and permits transmission.
Reason: A cell-autonomous antibacterial defense role mediated by autophagy; downstream of the core function and retained as non-core.
Supporting Evidence:
PMID:25646440
If autophagy is impaired, cell-to-cell transmission is inhibited, the host plasma membrane becomes compromised and the host cells die
|
|
GO:0030587
sorocarp development
|
IMP
PMID:14736886 Dictyostelium macroautophagy mutants vary in the severity of... |
KEEP AS NON CORE |
Summary: atg1 mutation causes severe developmental defects; the atg1-1 mutant fails to aggregate on bacterial lawns and arrests as loose mounds.
Reason: A well-established developmental requirement downstream of Atg1-dependent autophagy; retained as non-core.
Supporting Evidence:
PMID:14736886
does not aggregate on bacterial lawns
|
|
GO:0031288
sorocarp morphogenesis
|
IMP
PMID:14736886 Dictyostelium macroautophagy mutants vary in the severity of... |
KEEP AS NON CORE |
Summary: atg1 mutants produce aberrant fruiting-body morphology, reflecting a requirement for Atg1 in sorocarp morphogenesis.
Reason: A developmental morphogenesis phenotype downstream of Atg1-dependent autophagy; retained as non-core.
Supporting Evidence:
PMID:14736886
Mutations in the three genes produce aberrant development
|
|
GO:0004674
protein serine/threonine kinase activity
|
ISS
PMID:14736886 Dictyostelium macroautophagy mutants vary in the severity of... |
ACCEPT |
Summary: Ser/Thr kinase activity inferred from the conserved kinase domain; the core molecular function.
Reason: Consistent with the kinase-domain-dependent function directly demonstrated in Dictyostelium.
Supporting Evidence:
PMID:26246495
the serine/threonine kinase Atg1/ULK1
|
|
GO:0005737
cytoplasm
|
IDA
PMID:14736886 Dictyostelium macroautophagy mutants vary in the severity of... |
ACCEPT |
Summary: Cytoplasmic localization; consistent with the diffuse cytoplasmic distribution of Atg1 reported across studies.
Reason: Cytoplasmic localization of Atg1 is well established by direct evidence.
Supporting Evidence:
PMID:26246495
Atg1 fused to GFP has been shown previously to have a general cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
|
|
GO:0006995
cellular response to nitrogen starvation
|
IMP
PMID:14736886 Dictyostelium macroautophagy mutants vary in the severity of... |
KEEP AS NON CORE |
Summary: atg1 mutants show reduced survival during nitrogen starvation, linking Atg1 to the nitrogen-starvation response.
Reason: A supported starvation-response phenotype downstream of Atg1-dependent autophagy; retained as non-core.
Supporting Evidence:
PMID:14736886
reduced survival during nitrogen starvation
|
|
GO:0016236
macroautophagy
|
IMP
PMID:14736886 Dictyostelium macroautophagy mutants vary in the severity of... |
ACCEPT |
Summary: atg1 is required for macroautophagy in Dictyostelium, a core function.
Reason: Direct genetic evidence that Atg1 is required for macroautophagy; a core biological process.
Supporting Evidence:
PMID:14736886
genes are required for macroautophagy in Dictyostelium
|
|
GO:0030435
sporulation resulting in formation of a cellular spore
|
IMP
PMID:14736886 Dictyostelium macroautophagy mutants vary in the severity of... |
KEEP AS NON CORE |
Summary: Because Atg1 is required for normal fruiting-body development, spore formation is impaired in atg1 mutants; this is a downstream developmental consequence.
Reason: A developmental sporulation phenotype downstream of Atg1-dependent autophagy; retained as non-core.
Supporting Evidence:
PMID:14736886
Mutations in the three genes produce aberrant development
|
id: Q86CS2
gene_symbol: atg1
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:44689
label: Dictyostelium discoideum
description: >-
atg1 encodes the Dictyostelium discoideum ortholog of the Atg1/ULK1
serine/threonine protein kinase, the most upstream component of the
macroautophagy induction machinery. The protein has an N-terminal protein
kinase domain (residues ~7-266) followed by an asparagine/glutamine-rich
low-complexity region and a conserved C-terminal domain required for its
localization to forming autophagosomes. Atg1 is the catalytic subunit of the
Atg1 kinase complex (with Atg13 and Atg101), and its kinase activity initiates
phagophore/autophagosome formation. Because Dictyostelium undergoes
starvation-induced multicellular development that depends on autophagy for
nutrient mobilization, Atg1 is essential for aggregation and for normal
fruiting-body (sorocarp) formation, and it is required for the vacuolar
(autophagic) cell death of terminally differentiating cells. Atg1-dependent
autophagy also contributes to cell-autonomous defense against ingested
bacteria and yeasts and to nutrient and energy homeostasis, and the kinase
additionally influences macropinocytosis, cell size and nuclear division, gene
expression, and mitochondrial energy balance. Atg1 localizes predominantly to
the cytoplasm and cytosol, with a pool at the preautophagosomal structure
(phagophore assembly site) membrane.
existing_annotations:
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Cytoplasmic localization is correct and directly supported by experimental
evidence in Dictyostelium; Atg1-GFP shows a general cytoplasmic distribution.
action: ACCEPT
reason: Atg1 acts predominantly in the cytoplasm, consistent with direct localization
data and with its role as the cytoplasmic autophagy-initiating kinase.
supported_by:
- reference_id: PMID:26246495
supporting_text: Atg1 fused to GFP has been shown previously to have a general
cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
- term:
id: GO:0000045
label: autophagosome assembly
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Atg1 is the upstream kinase that initiates autophagosome formation, a
core conserved function directly demonstrated in Dictyostelium.
action: ACCEPT
reason: Kinase-dead Atg1 blocks functional autophagosome formation and Atg1 is
required for macroautophagy, making autophagosome assembly a core function.
supported_by:
- reference_id: PMID:17031001
supporting_text: In cells expressing dominant-negative DdAtg1, autophagosomes
are formed and accumulate but seem not to be functional
- term:
id: GO:0000423
label: mitophagy
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Mitophagy is a conserved ULK1/Atg1 selective-autophagy function, but
direct evidence in Dictyostelium is lacking; the one study of Atg1 and mitochondria
concluded an ancillary role in energy balance rather than direct organelle turnover.
action: KEEP_AS_NON_CORE
reason: The IBA transfer of mitophagy from ULK1 orthologs is plausible but not
demonstrated for Dictyostelium Atg1, where mitochondrial effects appear indirect;
retained as non-core pending direct evidence.
supported_by:
- reference_id: PMID:39056773
supporting_text: Atg1's effects on energy homeostasis indicate a peripheral
ancillary role in the mitochondrial signalling network, with effects on energy
balance rather than direct effects on electron transport chain function
- term:
id: GO:0010506
label: regulation of autophagy
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Atg1 is the induction-regulating kinase of the autophagy pathway, a core
conserved function.
action: ACCEPT
reason: As the catalytic subunit of the Atg1 complex, Atg1 controls the induction
of autophagy, consistent with this annotation.
supported_by:
- reference_id: PMID:26246495
supporting_text: The first steps of induction and nucleation are controlled
by the serine/threonine kinase Atg1/ULK1 and the class III PI3 K VPS34
- term:
id: GO:0042594
label: response to starvation
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Atg1-dependent autophagy is induced by and required for survival during
starvation, well supported in Dictyostelium.
action: ACCEPT
reason: atg1 mutants show reduced survival during nitrogen starvation, directly
linking Atg1 to the starvation response.
supported_by:
- reference_id: PMID:14736886
supporting_text: reduced survival during nitrogen starvation
- term:
id: GO:0061709
label: reticulophagy
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Reticulophagy (ER-phagy) is a conserved selective-autophagy branch inferred
from orthologs, but has not been demonstrated for Dictyostelium Atg1.
action: KEEP_AS_NON_CORE
reason: No direct evidence for ER-selective autophagy by Dictyostelium Atg1; retained
as a non-core phylogenetic inference.
- term:
id: GO:0000407
label: phagophore assembly site
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Atg1 acts at the phagophore assembly site (preautophagosomal structure),
where it initiates autophagosome formation.
action: ACCEPT
reason: Kinase-dead Atg1 colocalizes with the Atg8 marker of preautophagosomal
structures, supporting activity at this site.
supported_by:
- reference_id: PMID:17031001
supporting_text: colocalizes with red fluorescent protein (RFP)-tagged DdAtg8,
a marker of
- term:
id: GO:0005776
label: autophagosome
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Atg1 localizes to preautophagosomal structures and autophagosomes as
shown by colocalization with the Atg8 marker.
action: ACCEPT
reason: Direct colocalization of Atg1 with RFP-Atg8-labeled autophagosomes supports
this localization annotation.
supported_by:
- reference_id: PMID:17031001
supporting_text: a marker of preautophagosomal structures and autophagosomes
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: Atg1 is a serine/threonine protein kinase; this is the core molecular
function.
action: ACCEPT
reason: The conserved kinase domain and demonstrated kinase-dependent (dominant-negative
kinase-dead) function establish Ser/Thr kinase activity as the core molecular
function.
supported_by:
- reference_id: PMID:17031001
supporting_text: Kinase-negative DdAtg1 acts in a
- term:
id: GO:0034045
label: phagophore assembly site membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Atg1 associates with the phagophore assembly site (preautophagosomal
structure) membrane as a peripheral membrane protein.
action: ACCEPT
reason: Consistent with UniProt subcellular location (preautophagosomal structure
membrane, peripheral) and with Atg1 activity at the PAS.
supported_by:
- reference_id: PMID:17031001
supporting_text: a marker of preautophagosomal structures and autophagosomes
- term:
id: GO:0005829
label: cytosol
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Consistent with the observed diffuse cytoplasmic/cytosolic distribution
of Atg1.
action: ACCEPT
reason: Atg1-GFP shows a general cytoplasmic pattern, consistent with a cytosolic
pool.
supported_by:
- reference_id: PMID:26246495
supporting_text: Atg1 fused to GFP has been shown previously to have a general
cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
- term:
id: GO:0034727
label: piecemeal microautophagy of the nucleus
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: A yeast-derived selective microautophagy process; not demonstrated for
Dictyostelium Atg1.
action: KEEP_AS_NON_CORE
reason: No direct evidence in Dictyostelium; retained as a non-core phylogenetic
inference from fungal orthologs.
- term:
id: GO:0004672
label: protein kinase activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: General protein kinase activity, a correct parent term of the specific
Ser/Thr kinase activity.
action: ACCEPT
reason: Correct but less specific than protein serine/threonine kinase activity;
the more specific term is captured elsewhere.
supported_by:
- reference_id: PMID:17031001
supporting_text: these domains
are essential for autophagy and development
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: enables
review:
summary: Core molecular function, correctly assigned by automated methods.
action: ACCEPT
reason: Atg1 belongs to the APG1/unc-51/ULK1 Ser/Thr kinase subfamily; this is
the core molecular function.
supported_by:
- reference_id: PMID:26246495
supporting_text: the serine/threonine kinase Atg1/ULK1
- term:
id: GO:0005524
label: ATP binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: ATP binding is required for kinase catalysis and is supported by the conserved
ATP-binding motif in the kinase domain.
action: ACCEPT
reason: The protein has a canonical protein kinase ATP-binding site; ATP binding
is intrinsic to its catalytic function.
supported_by:
- reference_id: PMID:26246495
supporting_text: the serine/threonine kinase Atg1/ULK1
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Cytoplasmic localization from UniProt subcellular location mapping; correct.
action: ACCEPT
reason: Consistent with direct experimental evidence for cytoplasmic localization.
supported_by:
- reference_id: PMID:26246495
supporting_text: Atg1 fused to GFP has been shown previously to have a general
cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
- term:
id: GO:0034045
label: phagophore assembly site membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Preautophagosomal structure membrane localization from UniProt; consistent
with Atg1 activity at the PAS.
action: ACCEPT
reason: Matches UniProt subcellular location (preautophagosomal structure membrane)
and Atg1's role at the phagophore assembly site.
supported_by:
- reference_id: PMID:17031001
supporting_text: a marker of preautophagosomal structures and autophagosomes
- term:
id: GO:0106310
label: protein serine kinase activity
evidence_type: IEA
original_reference_id: GO_REF:0000116
qualifier: enables
review:
summary: Serine kinase activity assigned via Rhea reaction mapping; consistent
with the Ser/Thr kinase activity of Atg1.
action: ACCEPT
reason: Correct reflection of the phosphotransferase reaction catalyzed by this
Ser/Thr kinase.
supported_by:
- reference_id: PMID:26246495
supporting_text: the serine/threonine kinase Atg1/ULK1
- term:
id: GO:0071692
label: protein localization to extracellular region
evidence_type: IMP
original_reference_id: PMID:38986731
qualifier: involved_in
review:
summary: atg1 (with atg9) modulates the intracellular and extracellular amounts
of the adhesion protein CadA and the secreted counting factor CtnA during aggregation,
an autophagy-dependent secretion role.
action: KEEP_AS_NON_CORE
reason: The effect on extracellular protein levels is a downstream consequence
of Atg1-dependent autophagy and unconventional secretion, not a core molecular
function; retained as a non-core process.
supported_by:
- reference_id: PMID:38986731
supporting_text: The intracellular and extracellular amounts of CadA are modulated
by autophagy genes
- term:
id: GO:0005737
label: cytoplasm
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: located_in
review:
summary: Cytoplasmic localization inferred from orthologs; consistent with direct
Dictyostelium data.
action: ACCEPT
reason: Supported by direct experimental localization of Atg1 to the cytoplasm.
supported_by:
- reference_id: PMID:26246495
supporting_text: Atg1 fused to GFP has been shown previously to have a general
cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
- term:
id: GO:0034045
label: phagophore assembly site membrane
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: located_in
review:
summary: PAS membrane localization inferred from orthologs; consistent with Atg1
activity at the phagophore assembly site.
action: ACCEPT
reason: Matches UniProt subcellular location and Atg1's autophagy-initiating role.
supported_by:
- reference_id: PMID:17031001
supporting_text: a marker of preautophagosomal structures and autophagosomes
- term:
id: GO:0106310
label: protein serine kinase activity
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: enables
review:
summary: Serine kinase activity inferred from sequence similarity; consistent with
the core Ser/Thr kinase function.
action: ACCEPT
reason: Correct reflection of Atg1 kinase activity.
supported_by:
- reference_id: PMID:26246495
supporting_text: the serine/threonine kinase Atg1/ULK1
- term:
id: GO:0000902
label: cell morphogenesis
evidence_type: IMP
original_reference_id: PMID:39056773
qualifier: involved_in
review:
summary: atg1 null cells are consistently smaller and show altered nuclear division;
this reflects effects on cell size/division rather than a dedicated morphogenetic
program.
action: KEEP_AS_NON_CORE
reason: The cell-size phenotype is a pleiotropic consequence of altered autophagy
and growth/energy homeostasis, not a core function; retained as non-core.
supported_by:
- reference_id: PMID:39056773
supporting_text: the null mutant exhibited consistently smaller average cell
sizes when grown axenically
- term:
id: GO:0009267
label: cellular response to starvation
evidence_type: IDA
original_reference_id: PMID:39056773
qualifier: involved_in
review:
summary: Atg1 increases tolerance of Dictyostelium to starvation, consistent with
its role in starvation-induced autophagy.
action: KEEP_AS_NON_CORE
reason: A genuine, experimentally supported role, but downstream of the core kinase/autophagy
function; retained as non-core.
supported_by:
- reference_id: PMID:39056773
supporting_text: Atg1 increases the tolerance of D. discoideum to starvation
and cAMP treatment
- term:
id: GO:0030587
label: sorocarp development
evidence_type: IDA
original_reference_id: PMID:39056773
qualifier: involved_in
review:
summary: Altered atg1 expression produces smaller fruiting bodies and multi-tipped
aggregates, confirming a role in multicellular (sorocarp) development.
action: KEEP_AS_NON_CORE
reason: A pleiotropic developmental role that follows from Atg1-dependent autophagy
during starvation-induced development; retained as non-core.
supported_by:
- reference_id: PMID:39056773
supporting_text: both atg1 antisense inhibition and overexpression resulted in
smaller fruiting bodies
- term:
id: GO:0048548
label: regulation of pinocytosis
evidence_type: IMP
original_reference_id: PMID:39056773
qualifier: involved_in
review:
summary: Atg1 positively regulates macropinocytosis; the null mutant has a macropinocytic
defect and uptake correlates with atg1 expression.
action: KEEP_AS_NON_CORE
reason: A real, experimentally supported regulatory effect on macropinocytic uptake,
but a downstream/pleiotropic role rather than a core function.
supported_by:
- reference_id: PMID:39056773
supporting_text: the atg1 null mutant displayed a macropinocytic defect
- term:
id: GO:0010629
label: negative regulation of gene expression
evidence_type: IDA
original_reference_id: PMID:39056773
qualifier: involved_in
review:
summary: Overexpression data suggest Atg1 negatively regulates the prestalk marker
ecmA; the effect on individual genes was modest.
action: KEEP_AS_NON_CORE
reason: A downstream developmental gene-expression effect, supported but not a
core molecular function; retained as non-core.
supported_by:
- reference_id: PMID:39056773
supporting_text: This suggests that Atg1 negatively regulates prestalk gene (ecmA)
expression
- term:
id: GO:0009617
label: response to bacterium
evidence_type: IMP
original_reference_id: PMID:22575510
qualifier: involved_in
review:
summary: atg1 is required for LPS-enhanced clearance of phagocytosed bacteria,
linking Atg1-dependent autophagy to the antibacterial response.
action: KEEP_AS_NON_CORE
reason: A genuine cell-autonomous defense role mediated by autophagy, but downstream
of the core kinase/autophagy function; retained as non-core.
supported_by:
- reference_id: PMID:22575510
supporting_text: LPS pre-treatment did not enhance clearance of phagocytized
S. aureus in cells deficient for either atg1 or atg9
- term:
id: GO:0031152
label: aggregation involved in sorocarp development
evidence_type: IMP
original_reference_id: PMID:39056773
qualifier: involved_in
review:
summary: atg1-null cells are unable to aggregate, a hallmark of severe autophagy
impairment in Dictyostelium development.
action: KEEP_AS_NON_CORE
reason: An experimentally established developmental phenotype downstream of Atg1-dependent
autophagy; retained as non-core.
supported_by:
- reference_id: PMID:26246495
supporting_text: Amoebas in which Atg1 has been knocked out are unable to aggregate
- term:
id: GO:0043327
label: chemotaxis to cAMP
evidence_type: IMP
original_reference_id: PMID:39056773
qualifier: involved_in
review:
summary: This study measured cAMP/starvation survival and aggregation timing but
did not directly assay chemotaxis to cAMP; a direct chemotaxis role for Atg1
cannot be verified from the available text.
action: UNDECIDED
reason: The cited paper does not present a direct chemotaxis assay, and antisense
inhibition had no pronounced effect on aggregation; the supporting evidence for
a specific chemotaxis-to-cAMP function cannot be verified.
- term:
id: GO:0043457
label: regulation of cellular respiration
evidence_type: IDA
original_reference_id: PMID:39056773
qualifier: involved_in
review:
summary: Knockout of atg1 alters mitochondrial and non-mitochondrial respiration,
supporting a role in modulating cellular respiration.
action: KEEP_AS_NON_CORE
reason: An experimentally supported but indirect/peripheral effect on energy homeostasis,
not a core molecular function; retained as non-core.
supported_by:
- reference_id: PMID:39056773
supporting_text: knocking out atg1 caused reductions in basal mitochondrial and
non-mitochondrial respiration
- term:
id: GO:0043653
label: mitochondrial fragmentation involved in apoptotic process
evidence_type: IDA
original_reference_id: PMID:39056773
qualifier: involved_in
review:
summary: The cited study characterized mitochondrial membrane mass, potential,
ROS and respiration but did not demonstrate mitochondrial fragmentation as part
of an apoptotic process; Dictyostelium cell death is characteristically non-apoptotic.
action: UNDECIDED
reason: The specific term (apoptotic mitochondrial fragmentation) is not supported
by the available text and apoptosis is not an established Dictyostelium cell-death
mode; the basis for this annotation cannot be verified.
- term:
id: GO:0044351
label: macropinocytosis
evidence_type: IDA
original_reference_id: PMID:39056773
qualifier: involved_in
review:
summary: atg1-null cells display a macropinocytic defect and macropinocytic uptake
correlates positively with atg1 expression.
action: KEEP_AS_NON_CORE
reason: A genuine effect on macropinocytosis, but a downstream/pleiotropic role
rather than a core molecular function; retained as non-core.
supported_by:
- reference_id: PMID:39056773
supporting_text: macropinocytic uptake rates were positively correlated with
the atg1 expression index
- term:
id: GO:0004672
label: protein kinase activity
evidence_type: IDA
original_reference_id: PMID:17031001
qualifier: enables
review:
summary: Direct evidence that the Atg1 kinase domain is essential for function;
kinase-dead Atg1 acts as a dominant negative.
action: ACCEPT
reason: The kinase domain is essential for autophagy and development, and a kinase-negative
mutant is dominant-negative, directly demonstrating catalytic protein kinase
function.
supported_by:
- reference_id: PMID:17031001
supporting_text: these domains
are essential for autophagy and development
- term:
id: GO:0016236
label: macroautophagy
evidence_type: IMP
original_reference_id: PMID:17031001
qualifier: involved_in
review:
summary: Atg1 kinase and its conserved C-terminal domain are essential for macroautophagy
in Dictyostelium, a core function.
action: ACCEPT
reason: Kinase-dead Atg1 blocks functional autophagy and the domains are essential
for autophagy; macroautophagy is a core biological process for Atg1.
supported_by:
- reference_id: PMID:17031001
supporting_text: In cells expressing dominant-negative DdAtg1, autophagosomes
are formed and accumulate but seem not to be functional
- term:
id: GO:0048102
label: autophagic cell death
evidence_type: IMP
original_reference_id: PMID:15358773
qualifier: involved_in
review:
summary: atg1 disruption blocks autophagy and vacuolization in the developmental
vacuolar cell death model, showing Atg1 is required for autophagic (vacuolar)
cell death.
action: KEEP_AS_NON_CORE
reason: An experimentally supported developmental cell-death role that is downstream
of Atg1-dependent autophagy; retained as non-core.
supported_by:
- reference_id: PMID:15358773
supporting_text: led in atg1 mutant cells to impaired autophagy and to no vacuolization
- term:
id: GO:0008047
label: enzyme activator activity
evidence_type: IDA
original_reference_id: PMID:26246495
qualifier: enables
review:
summary: Atg1 positively regulates the activity of the pentose-phosphate-pathway
enzyme transketolase (TKT), with which it physically interacts; TKT activity
rises with Atg1 overexpression and falls in atg1-null or kinase-dead conditions.
action: KEEP_AS_NON_CORE
reason: Atg1 acts as a positive regulator of TKT activity (likely via its kinase
function), but this enzyme-activation role is a specialized regulatory link rather
than the core evolved molecular function; retained as non-core.
supported_by:
- reference_id: PMID:26246495
supporting_text: There is an increase in activity in cells overexpressing Atg1.
By contrast, TKT activity decreases in cells in which atg1 has been deleted
- term:
id: GO:0097300
label: programmed necrotic cell death
evidence_type: IDA
original_reference_id: PMID:17150370
qualifier: involved_in
review:
summary: This review describes that disrupting atg1 reveals a non-vacuolar (necrotic-like)
cell death pathway; necrotic death occurs in the absence of Atg1 rather than
requiring it, so a positive involvement of Atg1 in necrotic death is not clearly
supported.
action: UNDECIDED
reason: The relationship between Atg1 and necrotic cell death is indirect (necrosis
is unmasked when autophagic death is blocked); the supporting text is from a
review and does not establish that Atg1 is involved_in programmed necrotic death.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:31680241
qualifier: enables
review:
summary: Co-immunoprecipitation shows an AMPK-ATG1 interaction conserved in basal
autophagy. Bare 'protein binding' is uninformative; the meaningful content is
the specific interaction with AMPK.
action: KEEP_AS_NON_CORE
reason: Per curation guidance, generic protein binding is not retained as a core
function; the AMPK interaction is captured here as a non-core regulatory partnership.
supported_by:
- reference_id: PMID:31680241
supporting_text: Co-immunoprecipitation studies show conservation of the AMPK-ATG1
- term:
id: GO:0050830
label: defense response to Gram-positive bacterium
evidence_type: IDA
original_reference_id: PMID:28414774
qualifier: involved_in
review:
summary: This study focuses on the ESX-1/TORC1-dependent manipulation of autophagy
by Mycobacterium marinum; a specific, verifiable role for Atg1 in defense against
a Gram-positive bacterium is not evident from the available text.
action: UNDECIDED
reason: The cached text does not establish an Atg1-specific defense role against
Gram-positive bacteria; the annotation cannot be verified from the available
evidence.
- term:
id: GO:1905037
label: autophagosome organization
evidence_type: IMP
original_reference_id: PMID:28414774
qualifier: acts_upstream_of_or_within
review:
summary: Atg1 is required for autophagosome formation/organization, an essentially
core autophagy function; autophagosomes formed without functional Atg1 are aberrant.
action: KEEP_AS_NON_CORE
reason: Autophagosome organization is closely tied to Atg1's core autophagy-initiating
role; captured here as a non-core process-level annotation with the core function
recorded under macroautophagy/autophagosome assembly.
supported_by:
- reference_id: PMID:17031001
supporting_text: In cells expressing dominant-negative DdAtg1, autophagosomes
are formed and accumulate but seem not to be functional
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:26246495
qualifier: enables
review:
summary: Yeast two-hybrid and pull-down show Atg1 interacts with Atg13 and with
the pentose-phosphate enzyme transketolase (TKT). Bare 'protein binding' is uninformative;
the specific partners are the meaningful content.
action: KEEP_AS_NON_CORE
reason: Per curation guidance, generic protein binding is not retained as core;
the Atg13 and TKT interactions are better represented via the Atg1 complex membership
and the enzyme-activator annotation.
supported_by:
- reference_id: PMID:26246495
supporting_text: TKT–HA is efficiently pulled down by GFP-Atg1
- term:
id: GO:1990316
label: Atg1/ULK1 kinase complex
evidence_type: IDA
original_reference_id: PMID:26246495
qualifier: part_of
review:
summary: Atg1 is the catalytic subunit of the conserved Atg1-Atg13-Atg101 kinase
complex in Dictyostelium, confirmed by yeast two-hybrid and pull-down.
action: ACCEPT
reason: Direct evidence establishes the Atg1-Atg13-Atg101 core complex, making
Atg1/ULK1 kinase complex membership a core annotation.
supported_by:
- reference_id: PMID:26246495
supporting_text: The core of this assembly of proteins is formed by Atg1-Atg13-Atg101,
which seems to be conserved
- term:
id: GO:0001878
label: response to yeast
evidence_type: IMP
original_reference_id: PMID:27818653
qualifier: acts_upstream_of_or_within
review:
summary: atg1-null cells show altered (increased) ability to predate yeast, implicating
Atg1-dependent autophagy in the amoeba's interaction with yeast.
action: KEEP_AS_NON_CORE
reason: A downstream, autophagy-mediated host-microbe interaction phenotype; retained
as non-core.
supported_by:
- reference_id: PMID:27818653
supporting_text: mutants increase (atg1-, kil1-, kil2-) or decrease (atg6-) the
ability of the
- term:
id: GO:0035891
label: exit from host cell
evidence_type: IMP
original_reference_id: PMID:25646440
qualifier: acts_upstream_of_or_within
review:
summary: The autophagic machinery is required for nonlytic cell-to-cell transmission
(ejection) of mycobacteria; impairing autophagy blocks transmission.
action: KEEP_AS_NON_CORE
reason: A specialized host-pathogen role mediated by Atg1-dependent autophagy;
retained as non-core.
supported_by:
- reference_id: PMID:25646440
supporting_text: If autophagy is impaired, cell-to-cell transmission is
- term:
id: GO:0042742
label: defense response to bacterium
evidence_type: IMP
original_reference_id: PMID:25646440
qualifier: acts_upstream_of_or_within
review:
summary: Atg1-dependent autophagy contributes to control of intracellular mycobacteria;
autophagy impairment compromises the host and permits transmission.
action: KEEP_AS_NON_CORE
reason: A cell-autonomous antibacterial defense role mediated by autophagy; downstream
of the core function and retained as non-core.
supported_by:
- reference_id: PMID:25646440
supporting_text: If autophagy is impaired, cell-to-cell transmission is
inhibited, the host plasma membrane becomes compromised and the host cells
die
- term:
id: GO:0030587
label: sorocarp development
evidence_type: IMP
original_reference_id: PMID:14736886
qualifier: acts_upstream_of_or_within
review:
summary: atg1 mutation causes severe developmental defects; the atg1-1 mutant fails
to aggregate on bacterial lawns and arrests as loose mounds.
action: KEEP_AS_NON_CORE
reason: A well-established developmental requirement downstream of Atg1-dependent
autophagy; retained as non-core.
supported_by:
- reference_id: PMID:14736886
supporting_text: does not aggregate on bacterial lawns
- term:
id: GO:0031288
label: sorocarp morphogenesis
evidence_type: IMP
original_reference_id: PMID:14736886
qualifier: acts_upstream_of_or_within
review:
summary: atg1 mutants produce aberrant fruiting-body morphology, reflecting a requirement
for Atg1 in sorocarp morphogenesis.
action: KEEP_AS_NON_CORE
reason: A developmental morphogenesis phenotype downstream of Atg1-dependent autophagy;
retained as non-core.
supported_by:
- reference_id: PMID:14736886
supporting_text: Mutations in the three genes produce aberrant development
- term:
id: GO:0004674
label: protein serine/threonine kinase activity
evidence_type: ISS
original_reference_id: PMID:14736886
qualifier: enables
review:
summary: Ser/Thr kinase activity inferred from the conserved kinase domain; the
core molecular function.
action: ACCEPT
reason: Consistent with the kinase-domain-dependent function directly demonstrated
in Dictyostelium.
supported_by:
- reference_id: PMID:26246495
supporting_text: the serine/threonine kinase Atg1/ULK1
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IDA
original_reference_id: PMID:14736886
qualifier: located_in
review:
summary: Cytoplasmic localization; consistent with the diffuse cytoplasmic distribution
of Atg1 reported across studies.
action: ACCEPT
reason: Cytoplasmic localization of Atg1 is well established by direct evidence.
supported_by:
- reference_id: PMID:26246495
supporting_text: Atg1 fused to GFP has been shown previously to have a general
cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
- term:
id: GO:0006995
label: cellular response to nitrogen starvation
evidence_type: IMP
original_reference_id: PMID:14736886
qualifier: acts_upstream_of_or_within
review:
summary: atg1 mutants show reduced survival during nitrogen starvation, linking
Atg1 to the nitrogen-starvation response.
action: KEEP_AS_NON_CORE
reason: A supported starvation-response phenotype downstream of Atg1-dependent
autophagy; retained as non-core.
supported_by:
- reference_id: PMID:14736886
supporting_text: reduced survival during nitrogen starvation
- term:
id: GO:0016236
label: macroautophagy
evidence_type: IMP
original_reference_id: PMID:14736886
qualifier: acts_upstream_of_or_within
review:
summary: atg1 is required for macroautophagy in Dictyostelium, a core function.
action: ACCEPT
reason: Direct genetic evidence that Atg1 is required for macroautophagy; a core
biological process.
supported_by:
- reference_id: PMID:14736886
supporting_text: genes are required for macroautophagy in Dictyostelium
- term:
id: GO:0030435
label: sporulation resulting in formation of a cellular spore
evidence_type: IMP
original_reference_id: PMID:14736886
qualifier: acts_upstream_of_or_within
review:
summary: Because Atg1 is required for normal fruiting-body development, spore formation
is impaired in atg1 mutants; this is a downstream developmental consequence.
action: KEEP_AS_NON_CORE
reason: A developmental sporulation phenotype downstream of Atg1-dependent autophagy;
retained as non-core.
supported_by:
- reference_id: PMID:14736886
supporting_text: Mutations in the three genes produce aberrant development
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO
terms
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:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt
findings: []
- id: GO_REF:0000116
title: Automatic Gene Ontology annotation based on Rhea mapping
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:14736886
title: Dictyostelium macroautophagy mutants vary in the severity of their developmental
defects.
findings:
- statement: atg1, atg6 and atg8 are all required for macroautophagy in Dictyostelium,
and atg1 mutants show reduced survival during nitrogen starvation.
supporting_text: genes are required for macroautophagy in Dictyostelium
- statement: The atg1-1 mutant shows the most severe developmental defect, failing
to aggregate on bacterial lawns and arresting as loose mounds.
supporting_text: does not aggregate on bacterial lawns
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Primary characterization of the Dictyostelium atg1 knockout; establishes
the requirement of Atg1 for macroautophagy, starvation survival, and multicellular
development. Abstract-only in cache.
- id: PMID:15358773
title: Autophagy gene disruption reveals a non-vacuolar cell death pathway in Dictyostelium.
findings:
- statement: Disruption of atg1 impairs autophagy and abolishes vacuolization in
the developmental cell death model, though a non-vacuolar death still occurs.
supporting_text: led in atg1 mutant cells to impaired autophagy and to no vacuolization
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Shows atg1 is required for autophagic vacuolization; also reveals
an Atg1-independent non-vacuolar death pathway.
- id: PMID:17031001
title: Function of the Dictyostelium discoideum Atg1 kinase during autophagy and
development.
findings:
- statement: The kinase domain and conserved C-terminal domain of DdAtg1 are essential
for autophagy and development; a kinase-negative mutant is dominant-negative.
supporting_text: these domains
are essential for autophagy and development
- statement: Kinase-negative DdAtg1 colocalizes with RFP-Atg8, a marker of preautophagosomal
structures and autophagosomes.
supporting_text: a marker of preautophagosomal structures and autophagosomes
- statement: In dominant-negative Atg1 cells, autophagosomes form and accumulate
but are non-functional.
supporting_text: In cells expressing dominant-negative DdAtg1, autophagosomes
are formed and accumulate but seem not to be functional
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Key functional study of DdAtg1 kinase and C-terminal domains and
their role in autophagosome formation and localization.
- id: PMID:17150370
title: From autophagic to necrotic cell death in Dictyostelium.
findings: []
reference_review:
relevance: LOW
correctness: VERIFIED
review_notes: Review of Dictyostelium cell death; the necrotic pathway is unmasked
when autophagic death is blocked, so it does not establish a positive Atg1 role
in necrosis.
- id: PMID:22575510
title: Lipopolysaccharide induction of autophagy is associated with enhanced bactericidal
activity in Dictyostelium discoideum.
findings:
- statement: LPS-enhanced clearance of phagocytosed S. aureus requires atg1 and
atg9.
supporting_text: LPS pre-treatment did not enhance clearance of phagocytized S.
aureus in cells deficient for either atg1 or atg9
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Links Atg1-dependent autophagy to the antibacterial response.
- id: PMID:25646440
title: The autophagic machinery ensures nonlytic transmission of mycobacteria.
findings:
- statement: Impairing autophagy blocks nonlytic cell-to-cell transmission of mycobacteria
and compromises host membrane integrity.
supporting_text: If autophagy is impaired, cell-to-cell transmission is
inhibited, the host plasma membrane becomes compromised and the host cells die
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Autophagy machinery (including atg1) required for nonlytic mycobacterial
egress/transmission.
- id: PMID:26246495
title: Dissecting the function of Atg1 complex in Dictyostelium autophagy reveals
a connection with the pentose phosphate pathway enzyme transketolase.
findings:
- statement: The Dictyostelium Atg1 complex core is Atg1-Atg13-Atg101, more similar
to the mammalian than the yeast complex.
supporting_text: The core of this assembly of proteins is formed by Atg1-Atg13-Atg101,
which seems to be conserved
- statement: Atg1 physically interacts with transketolase (TKT) and positively regulates
its activity; TKT activity increases with Atg1 overexpression and decreases
in atg1-null or kinase-dead cells.
supporting_text: There is an increase in activity in cells overexpressing Atg1.
By contrast, TKT activity decreases in cells in which atg1 has been deleted
- statement: Atg1-GFP has a general cytoplasmic pattern with no specific puncta
localization.
supporting_text: Atg1 fused to GFP has been shown previously to have a general
cytoplasmic pattern in Dictyostelium cells with no specific puncta localization
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Defines the Dictyostelium Atg1-Atg13-Atg101 complex and the Atg1-transketolase
regulatory link; full text available.
- id: PMID:27818653
title: Dictyostelium discoideum as a Novel Host System to Study the Interaction
between Phagocytes and Yeasts.
findings:
- statement: atg1-null cells show altered ability to predate yeast, implicating
autophagy in the amoeba-yeast interaction.
supporting_text: mutants increase (atg1-, kil1-, kil2-) or decrease (atg6-) the
ability of the
reference_review:
relevance: LOW
correctness: VERIFIED
review_notes: Host-microbe interaction phenotype involving atg1.
- id: PMID:28414774
title: Mycobacterium marinum antagonistically induces an autophagic response while
repressing the autophagic flux in a TORC1- and ESX-1-dependent manner.
findings: []
reference_review:
relevance: LOW
correctness: UNVERIFIED
review_notes: Focuses on ESX-1/TORC1 manipulation of autophagy by M. marinum;
Atg1-specific role not verifiable from the cached text.
- id: PMID:31680241
title: AMPKα promotes basal autophagy induction in Dictyostelium discoideum.
findings:
- statement: The AMPK-ATG1 axis is conserved in basal autophagy, shown by co-immunoprecipitation.
supporting_text: Co-immunoprecipitation studies show conservation of the AMPK-ATG1
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: Establishes an AMPK-Atg1 regulatory interaction in Dictyostelium
basal autophagy. Abstract-only in cache.
- id: PMID:38986731
title: Trafficking of adhesion and aggregation-modulating proteins during the early
stages of Dictyostelium development.
findings:
- statement: Intracellular and extracellular amounts of the adhesion protein CadA
are modulated by autophagy genes atg1 and atg9.
supporting_text: The intracellular and extracellular amounts of CadA are modulated
by autophagy genes
reference_review:
relevance: LOW
correctness: VERIFIED
review_notes: Links atg1 to trafficking/secretion of adhesion and aggregation
proteins during aggregation. Abstract-only in cache.
- id: PMID:39056773
title: The Multifaceted Interactions of Dictyostelium Atg1 with Mitochondrial Function,
Endocytosis, Growth, and Development.
findings:
- statement: Atg1 positively regulates macropinocytosis; the null mutant has a macropinocytic
defect and uptake correlates with atg1 expression.
supporting_text: the atg1 null mutant displayed a macropinocytic defect
- statement: Atg1 increases tolerance of Dictyostelium to starvation and cAMP treatment.
supporting_text: Atg1 increases the tolerance of D. discoideum to starvation and
cAMP treatment
- statement: Altered atg1 expression yields smaller fruiting bodies and multi-tipped
aggregates, and Atg1 has a peripheral role in mitochondrial signalling affecting
respiration.
supporting_text: knocking out atg1 caused reductions in basal mitochondrial and
non-mitochondrial respiration
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Comprehensive phenotypic study of atg1 knockout, knockdown and overexpression
across growth, endocytosis, development, and mitochondrial homeostasis; full
text available.
core_functions:
- description: Atg1 is a serine/threonine protein kinase that acts as the catalytic
subunit of the Atg1/ULK1 kinase complex (Atg1-Atg13-Atg101) to initiate macroautophagy,
driving formation of the phagophore/autophagosome at the phagophore assembly site.
molecular_function:
id: GO:0004674
label: protein serine/threonine kinase activity
directly_involved_in:
- id: GO:0016236
label: macroautophagy
- id: GO:0000045
label: autophagosome assembly
locations:
- id: GO:0005737
label: cytoplasm
- id: GO:0000407
label: phagophore assembly site
- id: GO:0034045
label: phagophore assembly site membrane
in_complex:
id: GO:1990316
label: Atg1/ULK1 kinase complex
supported_by:
- reference_id: PMID:17031001
supporting_text: these domains
are essential for autophagy and development
- reference_id: PMID:26246495
supporting_text: The core of this assembly of proteins is formed by Atg1-Atg13-Atg101,
which seems to be conserved
- reference_id: PMID:14736886
supporting_text: genes are required for macroautophagy in Dictyostelium
- description: Through its kinase activity and role in initiating autophagy, Atg1 regulates
the induction of macroautophagy in response to nutrient/starvation status, making
it essential for starvation-induced multicellular (sorocarp) development in Dictyostelium.
molecular_function:
id: GO:0004674
label: protein serine/threonine kinase activity
directly_involved_in:
- id: GO:0010506
label: regulation of autophagy
- id: GO:0009267
label: cellular response to starvation
locations:
- id: GO:0005737
label: cytoplasm
supported_by:
- reference_id: PMID:26246495
supporting_text: The first steps of induction and nucleation are controlled
by the serine/threonine kinase Atg1/ULK1 and the class III PI3 K VPS34
- reference_id: PMID:39056773
supporting_text: Atg1 increases the tolerance of D. discoideum to starvation and
cAMP treatment