ATAD3A

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005739 mitochondrion	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference to mitochondrion is consistent with experimental localization of ATAD3A to mitochondria and the mitochondrial inner membrane/nucleoid region. Reason: ATAD3A is a mitochondrial AAA+ protein with multiple independent experimental localization studies. This cellular component captures a core location. Supporting Evidence: PMID:20154147 The N-terminal domain interacts with the OM PMID:20349121 ATAD3 is a mitochondrial inner membrane-associated protein
GO:0007005 mitochondrion organization	IBA GO_REF:0000033	ACCEPT	Summary: ATAD3A is required for normal mitochondrial network organization and dynamic inner/outer membrane interactions. Reason: Mitochondrion organization is a core process for ATAD3A, supported by dominant-negative and depletion phenotypes affecting mitochondrial morphology and membrane interactions. Supporting Evidence: PMID:20154147 ATAD3A regulates dynamic interactions between the mitochondrial OM and IM sensed by the cell fission machinery.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: ATP binding is consistent with the conserved AAA+ ATPase domain and mutational evidence from ATAD3A functional studies. Reason: ATP binding is an intrinsic molecular feature of the ATAD3A AAA+ ATPase domain and supports the core ATP hydrolysis activity. Supporting Evidence: PMID:20154147 positions the C-terminal AAA(+) ATPase domain in the matrix
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping to mitochondrial inner membrane is supported by experimental topology and membrane-association studies. Reason: The inner-membrane assignment is well supported and is a core location for ATAD3A function. Supporting Evidence: PMID:20154147 central transmembrane segment (TMS) anchors the protein in the IM PMID:20349121 ATAD3 is a mitochondrial inner membrane-associated protein
GO:0016887 ATP hydrolysis activity	IEA GO_REF:0000002	ACCEPT	Summary: ATP hydrolysis activity is consistent with ATAD3A being a functional AAA+ ATPase. Reason: The catalytic ATPase activity is a core molecular function of ATAD3A. Supporting Evidence: PMID:17210950 The ATPase of ATAD3 is functional PMID:20154147 positions the C-terminal AAA(+) ATPase domain in the matrix
GO:0042645 mitochondrial nucleoid	IEA GO_REF:0000044	ACCEPT	Summary: Mitochondrial nucleoid localization is supported by ATAD3A colocalization with mtDNA/nucleoids and effects on nucleoid organization. Reason: ATAD3A is not necessarily a core mtDNA-packaging protein in all nucleoids, but its nucleoid association and nucleoid-organizing role are well supported. Supporting Evidence: PMID:17210950 human ATAD3 is a component of many, but not all, mitochondrial nucleoids PMID:18063578 Several other metabolic proteins and chaperones identified in native nucleoids, including ATAD3, were not observed to cross-link to mtDNA
GO:0005515 protein binding	IPI PMID:22664726 ATAD3B is a human embryonic stem cell specific mitochondrial...	MARK AS OVER ANNOTATED	Summary: ATAD3A interacts with ATAD3B and HSPD1 in the cited study, but GO:0005515 protein binding is too generic to capture the functional implication. Reason: The interaction is real, but protein binding alone is uninformative and should not be treated as a molecular-function annotation for ATAD3A. The biologically meaningful context is mitochondrial homeostasis/nucleoid regulation. Supporting Evidence: PMID:22664726 ATAD3B associates with the ubiquitous ATAD3A species PMID:22664726 negatively regulates the interaction of ATAD3A with matrix nucleoid complexes
GO:0005515 protein binding	IPI PMID:30914652 ATAD3A oligomerization causes neurodegeneration by coupling ...	MARK AS OVER ANNOTATED	Summary: ATAD3A interacts with Drp1/DNM1L in neurodegeneration models, but the generic protein binding term is not an informative GO molecular function. Reason: The direct evidence supports a Drp1-ATAD3A mitochondrial-fragmentation mechanism, not a broad protein-binding function term. Supporting Evidence: PMID:30914652 ATAD3A as an interactor of mitochondrial fission GTPase, Drp1, in HD. PMID:30914652 ATAD3A plays a key role in neurodegeneration by linking Drp1-induced mitochondrial fragmentation to defective mtDNA maintenance
GO:0005739 mitochondrion	IEA GO_REF:0000107	ACCEPT	Summary: Orthology-based mitochondrion localization is consistent with experimental human ATAD3A localization. Reason: ATAD3A is robustly mitochondrial; this is a correct cellular-component annotation. Supporting Evidence: PMID:20332122 Expression of ATAD3A was detected by reverse transcription-polymerase chain reaction, immunoblotting, immunohistochemistry and confocal immunofluorescent microscopy. PMID:20349121 ATAD3 is a mitochondrial inner membrane-associated protein
GO:0005739 mitochondrion	IDA GO_REF:0000052	ACCEPT	Summary: HPA immunofluorescence mitochondrion localization agrees with the curated mitochondrial literature. Reason: The mitochondrion location is correct and supported by independent experimental studies. Supporting Evidence: PMID:20332122 Expression of ATAD3A was detected by reverse transcription-polymerase chain reaction, immunoblotting, immunohistochemistry and confocal immunofluorescent microscopy. PMID:20154147 The N-terminal domain interacts with the OM
GO:0005743 mitochondrial inner membrane	EXP PMID:18063578 The layered structure of human mitochondrial DNA nucleoids.	ACCEPT	Summary: Mitochondrial inner membrane localization is supported, with PMID:18063578 refining ATAD3A as peripheral to nucleoids rather than a core mtDNA-crosslinked protein. Reason: The cellular-component term is correct. The evidence should be interpreted as inner-membrane/nucleoid-associated localization, not necessarily direct mtDNA core binding. Supporting Evidence: PMID:18063578 Several other metabolic proteins and chaperones identified in native nucleoids, including ATAD3, were not observed to cross-link to mtDNA PMID:18063578 translation and complex assembly may occur in the peripheral region
GO:0005743 mitochondrial inner membrane	EXP PMID:20332122 ATPase family AAA domain-containing 3A is a novel anti-apopt...	ACCEPT	Summary: The lung adenocarcinoma study confirms experimental ATAD3A detection; mitochondrial inner-membrane localization is supported by the broader ATAD3A topology literature. Reason: The term captures a well-supported core cellular location, even though the cited paper focuses on cancer phenotypes. Supporting Evidence: PMID:20332122 Expression of ATAD3A was detected by reverse transcription-polymerase chain reaction, immunoblotting, immunohistochemistry and confocal immunofluorescent microscopy. PMID:20332122 Our results show that ATAD3A is the major form expressed in LADC.
GO:0016887 ATP hydrolysis activity	IMP PMID:39116259 PERK-ATAD3A interaction provides a subcellular safe haven fo...	ACCEPT	Summary: ATAD3A is a AAA+ ATPase. The cited PERK paper uses ATPase mutants to separate PERK inhibition from ATPase activity, while other ATAD3A studies support ATPase activity as core. Reason: ATP hydrolysis is an intrinsic ATAD3A molecular function. The specific PERK-inhibition mechanism appears ATPase-independent, but that does not invalidate ATAD3A ATPase activity. Supporting Evidence: PMID:17210950 The ATPase of ATAD3 is functional PMID:20154147 positions the C-terminal AAA(+) ATPase domain in the matrix
GO:0030291 protein serine/threonine kinase inhibitor activity	IDA PMID:39116259 PERK-ATAD3A interaction provides a subcellular safe haven fo...	KEEP AS NON CORE	Summary: ATAD3A inhibits PERK kinase signaling at mitochondria-ER contacts during ER stress. Reason: The PERK inhibitor activity is experimentally supported and biologically meaningful, but it is a context-specific stress-response function rather than the core AAA ATPase/nucleoid/mitochondrial-organization role. Supporting Evidence: PMID:39116259 ATAD3A interacted with protein kinase RNA-like endoplasmic reticulum kinase (PERK) PMID:39116259 ATAD3A binding attenuated local PERK signaling
GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site	IDA PMID:39116259 PERK-ATAD3A interaction provides a subcellular safe haven fo...	KEEP AS NON CORE	Summary: ATAD3A is active at mitochondria-associated ER membrane contact sites during ER stress through its PERK interaction. Reason: This contact-site localization is supported, but it describes a stress-regulated sublocation rather than the primary mitochondrial inner-membrane/nucleoid location. Supporting Evidence: PMID:39116259 PERK-ATAD3A interactions increased during ER stress, forming mitochondria-ER contact sites.
GO:1903898 negative regulation of PERK-mediated unfolded protein response	IDA PMID:39116259 PERK-ATAD3A interaction provides a subcellular safe haven fo...	KEEP AS NON CORE	Summary: ATAD3A negatively regulates local PERK-mediated unfolded-protein-response signaling to preserve mitochondrial protein synthesis during ER stress. Reason: This is a real, experimentally supported stress-context function, but it is secondary to the core mitochondrial AAA ATPase/nucleoid/organization functions. Supporting Evidence: PMID:39116259 ATAD3A binding attenuated local PERK signaling and rescued the expression of some mitochondrial proteins. PMID:39116259 active translation at mitochondria was significantly protected
GO:0005524 ATP binding	IMP PMID:20154147 The AAA+ ATPase ATAD3A controls mitochondrial dynamics at th...	ACCEPT	Summary: ATP binding is supported by ATAD3A AAA+ domain function and ATP-sensitive oligomer/membrane interaction phenotypes. Reason: This is a core molecular feature of the ATAD3A AAA+ ATPase. Supporting Evidence: PMID:20154147 positions the C-terminal AAA(+) ATPase domain in the matrix
GO:0005743 mitochondrial inner membrane	IDA PMID:20154147 The AAA+ ATPase ATAD3A controls mitochondrial dynamics at th...	ACCEPT	Summary: ATAD3A acts at mitochondrial inner/outer membrane contact regions, anchored in the mitochondrial inner membrane. Reason: The mitochondrial inner membrane is a core location for ATAD3A and is directly supported by topology experiments. Supporting Evidence: PMID:20154147 central transmembrane segment (TMS) anchors the protein in the IM PMID:20154147 ATAD3A is required for normal cell growth and cholesterol channeling at contact sites.
GO:0007005 mitochondrion organization	IMP PMID:20154147 The AAA+ ATPase ATAD3A controls mitochondrial dynamics at th...	ACCEPT	Summary: ATAD3A controls mitochondrial dynamics and organization at inner/outer membrane interfaces. Reason: Mitochondrion organization is one of the best-supported ATAD3A biological-process terms. Supporting Evidence: PMID:20154147 ATAD3A regulates dynamic interactions between the mitochondrial OM and IM sensed by the cell fission machinery.
GO:0016887 ATP hydrolysis activity	IMP PMID:20154147 The AAA+ ATPase ATAD3A controls mitochondrial dynamics at th...	ACCEPT	Summary: ATAD3A ATPase activity is supported by its AAA+ domain and functional studies. Reason: ATP hydrolysis activity is a core molecular function of ATAD3A. Supporting Evidence: PMID:17210950 The ATPase of ATAD3 is functional PMID:20154147 positions the C-terminal AAA(+) ATPase domain in the matrix
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput mitochondrial proteome evidence is consistent with ATAD3A being a mitochondrial protein. Reason: Although high-throughput, this annotation agrees with strong targeted evidence for mitochondrial localization. Supporting Evidence: PMID:34800366 A systematic analysis of mitochondrial protein dynamics is essential toward an understanding of mitochondrial proteostasis and its regulation under physiological and pathophysiological conditions. PMID:20349121 ATAD3 is a mitochondrial inner membrane-associated protein
GO:0006974 DNA damage response	IDA PMID:37832546 Mitochondrial DNA breaks activate an integrated stress respo...	MODIFY	Summary: PMID:37832546 supports ATAD3A participation in mtDNA-break-triggered integrated stress response signaling, not a broad DNA damage response or DNA repair role. Reason: The cited evidence places ATAD3A between damaged mitochondrial genomes and the inner membrane to promote DELE1-HRI/eIF2alpha integrated stress response signaling. A generic DNA damage response annotation is too broad. Proposed replacements: HRI-mediated signaling integrated stress response signaling Supporting Evidence: PMID:37832546 mtDSBs triggered the integrated stress response (ISR) PMID:37832546 we identified ATAD3A-a membrane-bound protein interacting with nucleoids-as potentially pivotal in relaying signals from impaired genomes to the inner mitochondrial membrane.
GO:0140468 HRI-mediated signaling	IDA PMID:37832546 Mitochondrial DNA breaks activate an integrated stress respo...	KEEP AS NON CORE	Summary: ATAD3A acts upstream of HRI-mediated signaling after mitochondrial DNA breaks. Reason: This signaling role is supported, but it is a stress-response context rather than the primary housekeeping role in mitochondrial organization/nucleoids/translation. Supporting Evidence: PMID:37832546 cells with mtDNA breaks activate the ISR in a DELE1-HRI-dependent manner PMID:37832546 ATAD3A, an AAA+ ATPase located at the inner mitochondrial membrane (IMM), as a factor that potentially signals from defective genomes to mitochondrial membranes.
GO:0005743 mitochondrial inner membrane	IDA PMID:20349121 Topological analysis of ATAD3A insertion in purified human m...	ACCEPT	Summary: Topological analysis supports ATAD3A as a mitochondrial inner membrane-associated protein with the C-terminal region facing the matrix. Reason: This is a well-supported core location. Supporting Evidence: PMID:20349121 ATAD3 is a mitochondrial inner membrane-associated protein PMID:20349121 the N-terminal part of ATAD3A is outside the inner membrane and that the C-terminal part is inside the matrix
GO:0005515 protein binding	IPI PMID:31522117 Structural Basis of Mitochondrial Scaffolds by Prohibitin Co...	MARK AS OVER ANNOTATED	Summary: ATAD3A participates in a mitochondrial scaffold/interactome with CLPB and MAVS-related antiviral signaling components, but GO:0005515 protein binding is too generic. Reason: The interaction evidence is better captured by the antiviral innate immune response context. Generic protein binding should not be retained as an informative ATAD3A molecular-function annotation. Supporting Evidence: PMID:31522117 AKAP1 and ATAD3A both co-immunoprecipitated with endogenous MAVS PMID:31522117 CLPB bridges PHB complexes (IMM) and MAVS (OMM) with the assistance of AKAP1 and ATAD3A at the IMS and invokes an immune response from the mitochondrial signalosome
GO:0140374 antiviral innate immune response	IMP PMID:31522117 Structural Basis of Mitochondrial Scaffolds by Prohibitin Co...	KEEP AS NON CORE	Summary: ATAD3A contributes to mitochondrial antiviral innate immune signaling in a CLPB/PHB/MAVS scaffold context. Reason: The antiviral phenotype is supported, but it is a specialized signaling context rather than the central ATAD3A mitochondrial organization/nucleoid/translation function. Supporting Evidence: PMID:31522117 depletion of these molecules in the cells exhibited strikingly defective antiviral innate immune responses against SeV infection PMID:31522117 CLPB bridges PHB complexes (IMM) and MAVS (OMM) with the assistance of AKAP1 and ATAD3A at the IMS and invokes an immune response from the mitochondrial signalosome
GO:0001558 regulation of cell growth	IMP PMID:20332122 ATPase family AAA domain-containing 3A is a novel anti-apopt...	KEEP AS NON CORE	Summary: ATAD3A depletion and expression changes affect lung adenocarcinoma survival and drug-response phenotypes. Reason: Cell-growth regulation is a real phenotype in the cited cancer context, but it is downstream of the mitochondrial role rather than a core ATAD3A process term. Supporting Evidence: PMID:20332122 Serum deprivation increased ATAD3A expression and drug resistance.
GO:0005739 mitochondrion	IDA PMID:20332122 ATPase family AAA domain-containing 3A is a novel anti-apopt...	ACCEPT	Summary: The cited lung adenocarcinoma study confirms ATAD3A detection, while independent topology evidence supports mitochondrial localization. Reason: The mitochondrion location is correct and consistent with many independent ATAD3A studies. Supporting Evidence: PMID:20332122 Expression of ATAD3A was detected by reverse transcription-polymerase chain reaction, immunoblotting, immunohistochemistry and confocal immunofluorescent microscopy. PMID:20349121 ATAD3 is a mitochondrial inner membrane-associated protein
GO:0043066 negative regulation of apoptotic process	IMP PMID:20332122 ATPase family AAA domain-containing 3A is a novel anti-apopt...	KEEP AS NON CORE	Summary: ATAD3A depletion sensitizes lung adenocarcinoma cells to cisplatin and is interpreted as anti-apoptotic in that cancer setting. Reason: The apoptotic phenotype is supported but cancer-contextual and downstream of mitochondrial homeostasis, not a core molecular function of ATAD3A. Supporting Evidence: PMID:20332122 Silencing of ATAD3A expression increased mitochondrial fragmentation and cisplatin sensitivity. PMID:20332122 These results suggest that ATAD3A could be an anti-apoptotic marker in LADC.
GO:0032042 mitochondrial DNA metabolic process	IMP PMID:22453275 Mitochondrial nucleoid interacting proteins support mitochon...	NEW	Summary: NEW annotation. ATAD3A supports mitochondrial DNA/nucleoid maintenance and replication-associated organization at the inner membrane. Reason: ATAD3A is repeatedly linked to mitochondrial nucleoid organization and mtDNA maintenance/replication. The current GOA captures mitochondrial nucleoid location but not the related mitochondrial DNA process. GO:0032042 is preferable to obsolete GO:0000002. Supporting Evidence: PMID:22453275 Altered ATAD3 expression also perturbs mtDNA maintenance and replication. PMID:17210950 altered the structure of mitochondrial nucleoids and led to the dissociation of mitochondrial DNA fragments held together by protein, specifically, ones containing the D-loop region file:human/ATAD3A/ATAD3A-deep-research-manual.md The core evidence supports mitochondrial organization, ATP hydrolysis, mitochondrial nucleoid organization, mtDNA maintenance, and support of mitochondrial protein synthesis.
GO:0032543 mitochondrial translation	IMP PMID:22453275 Mitochondrial nucleoid interacting proteins support mitochon...	NEW	Summary: NEW annotation. ATAD3A is required for mitochondrial protein synthesis and binds the mitochondrial ribosome. Reason: PMID:22453275 directly supports a role for ATAD3A in mitochondrial protein synthesis. This is part of the synthesized core ATAD3A function and is not currently represented in GOA. Supporting Evidence: PMID:22453275 Both proteins are demonstrated to be required for mitochondrial protein synthesis in human cultured cells, and the major binding partner of ATAD3 is the mitochondrial ribosome. file:human/ATAD3A/ATAD3A-deep-research-manual.md ATAD3A encodes a mitochondrial AAA+ ATPase located mainly at the mitochondrial inner membrane, enriched near inner/outer membrane contact sites and associated with mitochondrial nucleoids.

Gene Description

Existing Annotations Review

Core Functions

ATAD3A functions as a mitochondrial inner-membrane AAA+ ATPase/scaffold at contact-site and nucleoid-adjacent regions, supporting mitochondrial network organization, mtDNA/nucleoid organization, and mitochondrial protein synthesis.

References

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Deep Research

Manual

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Notes

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