Gene Ontology annotation through association of InterPro records with GO terms

InterPro AAA ATPase domains support the generic ATP-binding annotation, but more informative ATP hydrolysis and dislocase terms are available.

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

Manual transfer from mouse supports the AMPAR/postsynaptic annotation block, which is retained as non-core neuronal context.

GO_REF:0000033

Annotation inferences using phylogenetic trees

The IBA mitochondrial outer-membrane extraction and localization annotations align with direct ATAD1/Msp1 evidence.

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

UniProt location mapping correctly captures mitochondrial outer membrane and peroxisomal membrane localizations.

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

Ensembl Compara transfers mouse ATAD1/Thorase postsynaptic and receptor-trafficking annotations; these are not the conserved core proteostasis role.

GO_REF:0000116

Automatic Gene Ontology annotation based on Rhea mapping

Rhea mapping supports the translocase/dislocase reaction driven by ATP hydrolysis.

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

The generic membrane annotation should be replaced by specific membrane locations.

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

Combined automated ATPase and postsynaptic annotations are broadly compatible with UniProt but require core/non-core separation.

PMID:24843043

Msp1/ATAD1 maintains mitochondrial function by facilitating the degradation of mislocalized tail-anchored proteins.

Human ATAD1 limits mitochondrial mislocalization of PEX26 and GOS28 and is proposed as a conserved mitochondrial protein quality-control factor.

"human ATAD1 limits the mitochondrial mislocalization of PEX26 and GOS28"
ATAD1/Msp1 promotes extraction and degradation of mislocalized tail-anchored proteins.

"promote the extraction and degradation of mislocalized TA proteins"

PMID:19946888

Defining the membrane proteome of NK cells.

High-throughput membrane proteomics supports a broad membrane annotation but not a specific ATAD1 active compartment.

"approximately 40% of the identified proteins were predicted as plausible membrane proteins"

PMID:21525035

PEX14 is required for microtubule-based peroxisome motility in human cells.

Peroxisomal proteomics provides supporting context for peroxisomal membrane localization but not ATAD1 core function.

"Using mass spectrometric analysis, almost all known human peroxins involved in protein import were identified"

PMID:34800366

Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.

MitoCoP supports ATAD1 as part of the high-confidence human mitochondrial proteome.

"mitochondrial high-confidence proteome of >1,100 proteins"

PMID:29659736

ATAD1 encephalopathy and stiff baby syndrome: a recognizable clinical presentation.

Human ATAD1 disease provides context for neuronal/post-synaptic relevance, although this short article is not the primary mechanistic AMPAR trafficking paper.

"ATAD1 encephalopathy and stiff baby syndrome"

PMID:36409067

Collateral deletion of the mitochondrial AAA+ ATPase ATAD1 sensitizes cancer cells to proteasome dysfunction.

Human ATAD1 directly and selectively extracts the pro-apoptotic BH3-only protein BIM from mitochondria to inactivate it; extraction is ATP-dependent, requires membrane anchoring, and is lost in the catalytic E193Q mutant, supporting the dislocase/extractase activity.
ATAD1 lies adjacent to PTEN on chromosome 10q23 and is frequently co-deleted; ATAD1 loss sensitizes cells and xenografts to proteasome inhibitors via BIM-dependent apoptosis, a candidate therapeutic vulnerability rather than a core annotation.

PMID:35550246

Conserved structural elements specialize ATAD1 as a membrane protein extraction machine.

Cryo-EM of human ATAD1 bound to a peptide substrate shows it forms a hexameric AAA+ spiral that threads substrate through a central pore; pore-loop 1 aromatic residues are required to grip hydrophobic substrate and a C-terminal helix promotes oligomerization, specializing ATAD1 for membrane protein extraction.

PMID:31999255

Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction.

Cryo-EM structures of the ATAD1 ortholog Msp1 in complex with substrate establish that it forms hexameric spirals translocating substrate through a central aromatic pore, coupling ATP hydrolysis to membrane protein extraction.

PMID:32541053

The AAA+ ATPase Msp1 is a processive protein translocase with robust unfoldase activity.

The ATAD1 ortholog Msp1 is a processive, bidirectional protein translocase with unfoldase activity that threads substrates through its central pore; activity depends on the hexameric state and is inhibited by Pex3.

Reactome:R-HSA-9603775

PEX3:PEX19:class I PMP dissociates

Reactome records a PEX19/PEX3 class I peroxisomal membrane protein import step.

"The PEX19:PEX3:peroxisomal membrane protein complex dissociates"

Reactome:R-HSA-9603784

PEX19:class I PMP binds PEX3

Reactome places cytosolic PEX19 in this pathway step, explaining why cytosol should not be propagated as ATAD1 localization.

"Cytosolic PEX19 bound to a peroxisomal membrane protein"

Reactome:R-HSA-9603804

PEX19 binds class I peroxisomal membrane proteins

Reactome lists ATAD1 among class I peroxisomal membrane proteins bound by PEX19.

"ATAD1 (Liu et al. 2016)"

file:human/ATAD1/ATAD1-uniprot.txt

UniProtKB ATAD1_HUMAN record

UniProt summarizes ATAD1 as an outer mitochondrial transmembrane helix translocase with ATP-dependent dislocase activity.

"acts as a dislocase that mediates the ATP-dependent extraction of mistargeted tail-anchored transmembrane proteins"
UniProt records mitochondrial outer membrane, peroxisome membrane, and postsynaptic cell membrane localizations.

"SUBCELLULAR LOCATION: Mitochondrion outer membrane"

file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_candidate_additions.tsv

PN projected candidate additions report

The PN projection flags ATAD1 as a new-to-GOA candidate for mitochondrial protein catabolic process from the organelle-specific protein degradation class.

file:projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

PN mapping scrutiny report

The mitochondrial protein catabolic process mapping is class-level and requires manual gene-level review before changing a gene review.