protein
Atlastin-1
aka ATL-1
Gene
ATL1
Organism
Homo sapiens(9606)
Length
558 aa
Mass
63,544 Da
# Atlastin-1 Summary
Atlastin-1 (ATL1) is a membrane-anchored GTPase that mediates GTP-dependent fusion of endoplasmic reticulum membranes, maintaining the continuous ER network architecture (UniProt: Q8WXF7). The protein functions by forming homodimers on neighboring ER tubules that bind GTP and subsequently undergo conformational changes upon GTP hydrolysis to pull membranes together and drive fusion. After fusion completion and phosphate release, the homodimer disassembles and resets for new fusion cycles. ATL1 may also regulate Golgi biogenesis and indirectly support axonal development.
Mutations in ATL1 cause neurodegenerative disorders including autosomal dominant spastic paraplegia 3 (SPG3) and hereditary sensory neuropathy 1D (HSN1D), both characterized by progressive neurological decline (UniProt: Q8WXF7). These hereditary conditions underscore the protein's critical role in neuronal function and maintenance.
ATL1 is downregulated in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.725 (Chaparral AD proteomics). This reduction was observed in human post-mortem AD brain analyzed across multiple subcellular fractions using quantitative mass spectrometry, suggesting impaired ER network homeostasis may contribute to AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
not detected
P2
not detected
S2
not detected
S3
-0.725
Mean log₂FC across detected fractions: -0.725 (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
Atlastin-1 (ATL1) is a membrane-anchored GTPase that mediates the GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network. It facilitates the formation of three-way junctions where ER tubules intersect (PubMed:14506257, PubMed:18270207, PubMed:19665976, PubMed:27619977, PubMed:34817557, PubMed:38509071). Two atlastin-1 on neighboring ER tubules bind GTP and form loose homodimers through the GB1/RHD3-type G domains and 3HB regions. Upon GTP hydrolysis, the 3HB regions tighten, pulling the membranes together to drive their fusion. After fusion, the homodimer disassembles upon release of inorganic phosphate (Pi). Subsequently, GDP dissociates, resetting the monomers to a conformation ready for a new fusion cycle (PubMed:14506257, PubMed:21220294, PubMed:21368113, PubMed:23334294, PubMed:38509071). May also regulate more or less directly Golgi biogenesis (PubMed:17321752). Indirectly regulates axonal development (By similarity)
Disease associations
Spastic paraplegia 3, autosomal dominantSPG3
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
Neuropathy, hereditary sensory, 1DHSN1D
A disease characterized by adult-onset distal axonal sensory neuropathy leading to mutilating ulcerations as well as hyporeflexia. Some patients may show features suggesting upper neuron involvement.
Sources
Last updated 5/8/2026, 6:28:35 AM