protein
Outer mitochondrial transmembrane helix translocase
Gene
ATAD1
Organism
Homo sapiens(9606)
Length
361 aa
Mass
40,744 Da
ATAD1 (outer mitochondrial transmembrane helix translocase) is an ATP-dependent dislocase that removes mislocalized tail-anchored proteins from the mitochondrial outer membrane (UniProt: Q8NBU5). Beyond its role in mitochondrial protein quality control, ATAD1 regulates synaptic plasticity and learning and memory by controlling AMPA receptor surface expression and recycling in an ATPase-dependent manner.
ATAD1 is implicated in hyperekplexia 4 (HKPX4), a severe autosomal recessive neurological disorder characterized by early-onset seizures and developmental failure (UniProt: Q8NBU5). The protein's dual function in mitochondrial homeostasis and synaptic plasticity positions it at the intersection of cellular energy metabolism and neuronal signaling.
In Alzheimer's disease, ATAD1 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.25 across the measured subcellular fractions (Chaparral AD proteomics). This reduction may impair both mitochondrial protein quality control and AMPAR-mediated synaptic plasticity, processes implicated in AD pathogenesis.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.250
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.2498 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Outer mitochondrial translocase required to remove mislocalized tail-anchored transmembrane proteins on mitochondria (PubMed:24843043). Specifically recognizes and binds tail-anchored transmembrane proteins: acts as a dislocase that mediates the ATP-dependent extraction of mistargeted tail-anchored transmembrane proteins from the mitochondrion outer membrane (By similarity). Also plays a critical role in regulating the surface expression of AMPA receptors (AMPAR), thereby regulating synaptic plasticity and learning and memory (By similarity). Required for NMDA-stimulated AMPAR internalization and inhibition of GRIA1 and GRIA2 recycling back to the plasma membrane; these activities are ATPase-dependent (By similarity)
Disease associations
Hyperekplexia 4HKPX4
An autosomal recessive severe neurologic disorder apparent from birth. HKPX4 is characterized by little if any development, hypertonia, early-onset refractory seizures in some patients, and respiratory failure resulting in early death, mostly in the first months of life.
Sources
Last updated 5/8/2026, 6:28:56 AM