protein
AP-1 complex subunit sigma-1A
Gene
AP1S1
Organism
Homo sapiens(9606)
Length
158 aa
Mass
18,733 Da
AP1S1 encodes AP-1 complex subunit sigma-1A, a 158-amino-acid protein that functions as a component of the clathrin-associated adaptor protein complex 1. This complex mediates protein sorting in the late-Golgi and trans-Golgi network (TGN) by recruiting clathrin to membranes and recognizing sorting signals within transmembrane cargo molecules (UniProt: P61966).
The protein operates in vesicular trafficking pathways critical for protein delivery and compartmentalization. Mutations in AP1S1 are associated with MEDNIK syndrome, a severe neurodevelopmental and systemic disorder marked by psychomotor retardation, peripheral neuropathy, and sensorineural hearing loss (UniProt: P61966).
AP1S1 is downregulated in Alzheimer's disease brain tissue. Post-mortem AD brain samples showed reduced AP1S1 levels compared to age-matched controls (mean log2 fold-change: −1.62), derived from quantitative proteomics across subcellular fractions (Chaparral AD proteomics). This downregulation may reflect compromised vesicular trafficking and protein sorting dysfunction in 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
-1.617
S3
not detected
Mean log₂FC across detected fractions: -1.6171 (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
Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules
Disease associations
MEDNIK syndromeMEDNIK
A disorder characterized by erythematous skin lesions and hyperkeratosis, severe psychomotor retardation, peripheral neuropathy, sensorineural hearing loss, together with elevated very-long-chain fatty acids and severe congenital diarrhea.
Sources
Last updated 5/8/2026, 6:32:29 AM