ATAD1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0140570 extraction of mislocalized protein from mitochondrial outer membrane	IBA GO_REF:0000033	ACCEPT	Summary: This is the most specific existing biological-process annotation for the conserved ATAD1/Msp1 pathway. Reason: The IBA call matches direct human/yeast evidence that ATAD1/Msp1 limits accumulation of mistargeted tail-anchored proteins on mitochondria and promotes their extraction and degradation. This should be retained as a core function and is more precise than the PN-projected parent process. Supporting Evidence: PMID:24843043 human ATAD1 limits the mitochondrial mislocalization of PEX26 and GOS28 PMID:24843043 conserved members of the mitochondrial protein quality control system that might promote the extraction and degradation of mislocalized TA proteins PMID:35550246 removes mislocalized membrane proteins, as well as stuck import substrates from the mitochondrial outer membrane, facilitating their re-insertion into their cognate organelles and maintaining mitochondria's protein import capacity. In doing so, it helps to maintain proteostasis in mitochondria
GO:0005741 mitochondrial outer membrane	IBA GO_REF:0000033	ACCEPT	Summary: ATAD1 is an outer-mitochondrial-membrane anchored AAA+ dislocase. Reason: The mitochondrial outer membrane is the active location for ATAD1-mediated removal of mistargeted tail-anchored proteins. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane PMID:24843043 Msp1 limits the accumulation of mislocalized TA proteins on mitochondria
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ATAD1 has a canonical AAA ATPase domain and predicted ATP-binding residues. Reason: ATP binding is accurate but less informative than ATP hydrolysis activity and membrane protein dislocase activity, which capture the functional mechanism. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt /ligand="ATP"
GO:0005741 mitochondrial outer membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping correctly places ATAD1 in the mitochondrial outer membrane. Reason: This is the core membrane location for the dislocase function. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion outer membrane
GO:0005778 peroxisomal membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt reports peroxisomal membrane localization, but the reviewed core function is mitochondrial outer-membrane protein extraction. Reason: Keep this localization as supported non-core context. Current evidence does not establish peroxisomal membrane extraction as ATAD1's main conserved function. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Peroxisome membrane {ECO:0000269\|PubMed:24843043}
GO:0016020 membrane	IEA GO_REF:0000117	MODIFY	Summary: ATAD1 is a membrane protein, but the generic term loses the informative mitochondrial outer-membrane and peroxisomal-membrane localizations. Reason: Replace the generic membrane annotation with the specific experimentally supported membrane locations. Proposed replacements: mitochondrial outer membrane peroxisomal membrane Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Mitochondrion outer membrane file:human/ATAD1/ATAD1-uniprot.txt Peroxisome membrane
GO:0016887 ATP hydrolysis activity	IEA GO_REF:0000120	ACCEPT	Summary: ATP hydrolysis is the enzymatic activity that powers ATAD1 dislocase function. The cryo-EM structures of human ATAD1 (PDB 7UPR with ATP/Mg; 7UPT with ADP+ATP/Mg) capture the hexameric AAA+ assembly engaging a peptide substrate, consistent with ATP-hydrolysis-driven substrate translocation through the central pore. Reason: Retain this molecular-function annotation as a core activity of the AAA+ ATPase. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt ATAD1-catalyzed ATP hydrolysis PMID:35550246 extract hydrophobic membrane proteins from the lipid bilayer...utilization of multiple aromatic amino acids to firmly grip the substrate in the central pore
GO:0045211 postsynaptic membrane	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Postsynaptic localization is transferred from mouse Thorase/Atad1 biology and is relevant to the AMPA receptor trafficking phenotype. Reason: Keep as non-core neuronal context. The conserved core activity is membrane protein extraction at the mitochondrial outer membrane. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Postsynaptic cell membrane PMID:29659736 ATAD1 encephalopathy and stiff baby syndrome
GO:0140567 membrane protein dislocase activity	IEA GO_REF:0000116	ACCEPT	Summary: Membrane protein dislocase activity captures the core molecular function of ATAD1 more informatively than ATP binding alone. The cryo-EM structures of human ATAD1 (PDB 7UPR/7UPT) bound to a peptide substrate show a hexameric AAA+ spiral that grips the substrate in its central pore via conserved aromatic pore-loop 1 residues, directly visualizing the extraction/dislocase mechanism. Reason: UniProt describes ATAD1 as a dislocase that mediates ATP-dependent extraction of mistargeted tail-anchored transmembrane proteins; the Rhea mapping is therefore biologically appropriate. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt acts as a dislocase that mediates the ATP-dependent extraction of mistargeted tail-anchored transmembrane proteins PMID:35550246 removes mislocalized membrane proteins, as well as stuck import substrates from the mitochondrial outer membrane...utilization of multiple aromatic amino acids to firmly grip the substrate in the central pore...both aromatic amino acids in pore-loop 1 are required for ATAD1's function and cannot be substituted by aliphatic amino acids
GO:0002092 positive regulation of receptor internalization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This automated transfer reflects AMPA receptor internalization biology in the Thorase/Atad1 literature. Reason: Retain as a non-core neuronal receptor-trafficking process. It is not the primary conserved proteostasis function emphasized by the direct ATAD1 mitochondrial evidence. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Required for NMDA-stimulated AMPAR internalization
GO:0007612 learning	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Learning is a high-level organismal phenotype transferred from mouse Thorase/Atad1 studies. Reason: The term is too far downstream for a human ATAD1 gene-function review. The mechanistic neuronal annotations should be retained instead of treating learning as a core ATAD1 function. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt thereby regulating synaptic plasticity and learning
GO:0007613 memory	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Memory is a high-level behavioral consequence inferred from mouse Thorase/Atad1 studies. Reason: This phenotype-level term is too indirect for the core human annotation set. AMPAR receptor trafficking terms are more mechanistically useful. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt learning and memory (By similarity)
GO:0051967 negative regulation of synaptic transmission, glutamatergic	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This term summarizes the inferred synaptic consequence of ATAD1-dependent AMPAR trafficking. Reason: The annotation is plausible for neuronal ATAD1/Thorase biology but is secondary to the conserved mitochondrial dislocase/protein-quality-control function. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt regulating synaptic plasticity
GO:0098794 postsynapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Postsynapse is a transferred neuronal location consistent with the AMPAR-trafficking model. Reason: Keep as non-core neuronal context; it should not displace the mitochondrial outer membrane as the principal active location. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Postsynaptic cell membrane
GO:0098978 glutamatergic synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Glutamatergic synapse is a transferred neuronal location for the AMPAR-trafficking role. Reason: Keep as non-core context because the mechanistic evidence is by similarity and disease context rather than direct human localization. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Required for NMDA-stimulated AMPAR internalization
GO:0099149 regulation of postsynaptic neurotransmitter receptor internalization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: This is the most specific of the transferred receptor-internalization annotations. Reason: Retain as non-core neuronal context. It is mechanistically more appropriate than learning or memory but remains secondary to ATAD1's conserved membrane protein dislocase role. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Required for NMDA-stimulated AMPAR internalization
GO:0045211 postsynaptic membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: The manual transfer from mouse supports a neuronal postsynaptic membrane context. Reason: Keep as non-core because ATAD1's best-supported conserved location is the mitochondrial outer membrane. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Postsynaptic cell membrane
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	MODIFY	Summary: The MitoCoP proteomics study supports mitochondrial assignment, but the more precise location for ATAD1 is the mitochondrial outer membrane. Reason: Replace the broad mitochondrion term with mitochondrial outer membrane when representing ATAD1's active localization. Proposed replacements: mitochondrial outer membrane Supporting Evidence: PMID:34800366 mitochondrial high-confidence proteome of >1,100 proteins file:human/ATAD1/ATAD1-uniprot.txt Mitochondrion outer membrane
GO:0016887 ATP hydrolysis activity	ISS GO_REF:0000024	ACCEPT	Summary: ATP hydrolysis activity is conserved across ATAD1/Msp1 orthologs and powers dislocation/extraction. Reason: Retain as a core molecular function of the AAA+ ATPase. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt ATAD1-catalyzed ATP hydrolysis
GO:0005741 mitochondrial outer membrane	IDA PMID:24843043 Msp1/ATAD1 maintains mitochondrial function by facilitating ...	ACCEPT	Summary: Direct ATAD1 work supports mitochondrial localization for the protein quality-control function. Reason: The mitochondrial outer membrane is the site from which ATAD1 extracts mistargeted tail-anchored proteins. Supporting Evidence: PMID:24843043 Msp1 limits the accumulation of mislocalized TA proteins on mitochondria file:human/ATAD1/ATAD1-uniprot.txt Mitochondrion outer membrane
GO:0005778 peroxisomal membrane	IDA PMID:24843043 Msp1/ATAD1 maintains mitochondrial function by facilitating ...	KEEP AS NON CORE	Summary: Peroxisomal membrane localization is supported, but the direct functional evidence in this paper centers on mitochondrial mislocalization and mitochondrial quality control. Reason: Keep the location as supported non-core context. Do not infer an equivalent peroxisomal extraction function without direct evidence. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Peroxisome membrane {ECO:0000269\|PubMed:24843043}
GO:0140570 extraction of mislocalized protein from mitochondrial outer membrane	IDA PMID:24843043 Msp1/ATAD1 maintains mitochondrial function by facilitating ...	ACCEPT	Summary: Direct ATAD1/Msp1 evidence supports extraction of mislocalized tail-anchored proteins from mitochondria. Reason: This term captures the direct, specific ATAD1 biological process and is the best annotation for the PN-relevant mitochondrial quality-control role. Supporting Evidence: PMID:24843043 human ATAD1 limits the mitochondrial mislocalization of PEX26 and GOS28 PMID:24843043 promote the extraction and degradation of mislocalized TA proteins
GO:0005778 peroxisomal membrane	TAS Reactome:R-HSA-9603775	KEEP AS NON CORE	Summary: Reactome treats ATAD1 as a class I peroxisomal membrane protein in the PEX19/PEX3 import pathway. Reason: Keep as non-core localization/pathway context. This does not change the core function from mitochondrial outer-membrane dislocation. Supporting Evidence: Reactome:R-HSA-9603804 Human class I peroxisomal membrane proteins that are bound by PEX19 include Reactome:R-HSA-9603804 ATAD1 (Liu et al. 2016)
GO:0005829 cytosol	TAS Reactome:R-HSA-9603775	REMOVE	Summary: The cytosol localization appears to come from the PEX19 cytosolic step in peroxisomal membrane protein import rather than ATAD1 itself. Reason: ATAD1 is a single-pass membrane protein with mitochondrial outer membrane, peroxisomal membrane, and postsynaptic membrane annotations; cytosol is not an appropriate cellular-component annotation for the gene product. Supporting Evidence: Reactome:R-HSA-9603804 In the cytosol, PEX19 binds newly synthesized class I peroxisomal membrane proteins file:human/ATAD1/ATAD1-uniprot.txt Single-pass membrane protein
GO:0005829 cytosol	TAS Reactome:R-HSA-9603784	REMOVE	Summary: This Reactome cytosol annotation reflects cytosolic PEX19-cargo handling, not a soluble ATAD1 pool. Reason: Cytosol is inappropriate for ATAD1 because the protein is membrane anchored. The reaction can remain pathway context, but not as an ATAD1 cellular-component annotation. Supporting Evidence: Reactome:R-HSA-9603784 Cytosolic PEX19 bound to a peroxisomal membrane protein file:human/ATAD1/ATAD1-uniprot.txt Single-pass membrane protein
GO:0005829 cytosol	TAS Reactome:R-HSA-9603804	REMOVE	Summary: Reactome explicitly places PEX19 in the cytosol; ATAD1 is one of the membrane protein cargos listed in the same pathway context. Reason: The cytosolic reaction context should not be propagated as ATAD1 cytosolic localization. Supporting Evidence: Reactome:R-HSA-9603804 In the cytosol, PEX19 binds newly synthesized class I peroxisomal membrane proteins Reactome:R-HSA-9603804 ATAD1 (Liu et al. 2016)
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MODIFY	Summary: The high-throughput NK-cell membrane proteome annotation supports ATAD1 as membrane-associated but is less specific than curated subcellular locations. Reason: Replace the broad membrane term with mitochondrial outer membrane and peroxisomal membrane where relevant. Proposed replacements: mitochondrial outer membrane peroxisomal membrane Supporting Evidence: PMID:19946888 approximately 40% of the identified proteins were predicted as plausible membrane proteins file:human/ATAD1/ATAD1-uniprot.txt Mitochondrion outer membrane
GO:0005778 peroxisomal membrane	HDA PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ...	KEEP AS NON CORE	Summary: The peroxisomal proteomics/co-complex study is compatible with ATAD1 peroxisomal membrane localization, but it does not define the main ATAD1 function. Reason: Keep as non-core localization. The peroxisomal evidence is useful but weaker for functional inference than the direct mitochondrial quality-control evidence. Supporting Evidence: PMID:21525035 Using mass spectrometric analysis, almost all known human peroxins involved in protein import were identified file:human/ATAD1/ATAD1-uniprot.txt Peroxisome membrane
GO:0002092 positive regulation of receptor internalization	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Manual transfer from mouse captures ATAD1/Thorase-dependent AMPAR internalization. Reason: Keep as a secondary neuronal function. The more specific postsynaptic neurotransmitter receptor internalization term is preferable when representing this axis. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Required for NMDA-stimulated AMPAR internalization
GO:0007612 learning	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Learning is a downstream phenotype from transferred mouse evidence. Reason: Do not retain behavioral phenotype terms as core human ATAD1 function. Receptor trafficking and synaptic transmission annotations better capture the mechanistic neuronal axis. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt thereby regulating synaptic plasticity and learning
GO:0007613 memory	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Memory is a downstream behavioral phenotype from transferred mouse evidence. Reason: The term is too high-level and indirect for ATAD1's gene-function core. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt learning and memory (By similarity)
GO:0045211 postsynaptic membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Manual orthology transfer supports a postsynaptic membrane context. Reason: Retain as secondary neuronal localization; mitochondrial outer membrane remains the principal location for the core dislocase function. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt Postsynaptic cell membrane
GO:0051967 negative regulation of synaptic transmission, glutamatergic	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: This GOA row was missing from the initial seeded review YAML and was added manually from ATAD1-goa.tsv to complete review coverage. The term is a transferred synaptic consequence of ATAD1/Thorase AMPAR trafficking. Reason: Retain as non-core neuronal context rather than as a defining ATAD1 function. It is more mechanistic than learning/memory but still secondary to the conserved mitochondrial protein-quality-control role. Supporting Evidence: file:human/ATAD1/ATAD1-uniprot.txt regulating synaptic plasticity
GO:0035694 mitochondrial protein catabolic process	TAS PMID:24843043 Msp1/ATAD1 maintains mitochondrial function by facilitating ...	NEW	Summary: The PN projection proposed mitochondrial protein catabolic process for ATAD1 from the class-level organelle-specific protein degradation bucket. Direct ATAD1 evidence supports this as a broad downstream process because ATAD1 facilitates clearance of mislocalized mitochondrial outer-membrane tail-anchored proteins. Reason: Add conservatively as a broad PN-relevant candidate, supported by the traceable author statement and abstract-level evidence in the direct ATAD1 degradation paper. TAS is used rather than IMP because the cached evidence supports the process as a reported downstream outcome, while the stricter perturbation evidence for protein-level accumulation is from ATAD1(-/-) mouse tissue. This should not replace the more specific existing GO:0140570 extraction annotation, which remains the preferred core mechanistic process. Supporting Evidence: PMID:24843043 facilitating the degradation of mislocalized tail-anchored proteins PMID:24843043 GOS28 protein level is also increased in ATAD1(-/-) mouse tissues

Gene Description

Existing Annotations Review

Core Functions

ATAD1 is an ATP-dependent membrane protein dislocase that extracts mistargeted tail-anchored proteins from the mitochondrial outer membrane. This is the main conserved molecular role of the protein.

ATAD1 hydrolyzes ATP through its AAA+ ATPase domain to power extraction of membrane protein substrates and disassembly of selected protein complexes.

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