protein
Atlastin-3
aka AT3, ATL-3
Gene
ATL3
Organism
Homo sapiens(9606)
Length
541 aa
Mass
60,542 Da
Atlastin-3 (ATL3) is a membrane-anchored GTPase that mediates GTP-dependent fusion of endoplasmic reticulum (ER) membranes, maintaining the continuous ER network architecture. The protein facilitates three-way junction formation where ER tubules intersect through a GTP-dependent mechanism involving homodimer assembly, membrane pulling, and subsequent disassembly upon GTP hydrolysis (UniProt: Q6DD88).
ATL3 is primarily associated with the secretory pathway and ER homeostasis. In addition to its housekeeping role, mutations in ATL3 cause hereditary sensory neuropathy 1F (HSN1F), an autosomal dominant condition characterized by distal sensory impairment and foot ulceration beginning in the second or third decade (UniProt: Q6DD88).
In Alzheimer's Disease, ATL3 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.44 across two subcellular fractions detected via TMT-labeled quantitative proteomics (Chaparral AD proteomics). This elevation suggests altered ER membrane dynamics or organellar stress responses may be relevant to AD pathophysiology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
+0.567
P2
+0.316
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: +0.4414 (2 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-3 (ATL3) 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:18270207, PubMed:19665976, PubMed:24459106, PubMed:27619977, PubMed:37102997). Two atlastin-3 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 (By similarity)
Disease associations
Neuropathy, hereditary sensory, 1FHSN1F
An autosomal dominant sensory neuropathy affecting the lower limbs. Distal sensory impairment becomes apparent during the second or third decade of life, resulting in painless ulceration of the feet with poor healing, which can progress to osteomyelitis, bone destruction, and amputation. There is no autonomic involvement, spasticity, or cognitive impairment.
Sources
Last updated 5/8/2026, 6:28:13 AM