protein
Argininosuccinate synthase
Gene
ASS1
Organism
Homo sapiens(9606)
Length
412 aa
Mass
46,530 Da
Argininosuccinate synthase (ASS1) is a 412-amino acid enzyme that catalyzes the condensation of aspartate, citrulline, and ATP to form argininosuccinate, a key step in both the urea cycle and arginine biosynthesis (UniProt: P00966). The enzyme detoxifies ammonia produced during protein catabolism by converting it to urea in the liver, while also supplying arginine to most body tissues. Loss-of-function mutations cause citrullinemia type 1 (CTLN1, MIM 215700), an autosomal recessive urea cycle disorder presenting with hyperammonemia, seizures, and developmental encephalopathy.
In Alzheimer's disease brain tissue, ASS1 is upregulated relative to age-matched controls (mean log2 fold-change +1.35; Chaparral AD proteomics), based on quantitative proteomics of post-mortem human brain across multiple subcellular fractions. This upregulation may reflect altered ammonia metabolism or increased arginine demand in the context of neurodegeneration, though the functional significance in AD pathogenesis requires further investigation. No additional disease associations are currently curated for this protein.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
+1.352
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: +1.3522 (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
One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals. Catalyzes the formation of arginosuccinate from aspartate, citrulline and ATP and together with ASL it is responsible for the biosynthesis of arginine in most body tissues
Disease associations
Citrullinemia 1CTLN1
The classic form of citrullinemia, an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. It is a disorder of the urea cycle, usually manifesting in the first few days of life. Affected infants appear normal at birth, but as ammonia builds up in the body they present symptoms such as lethargy, poor feeding, vomiting, seizures and loss of consciousness. Less commonly, a milder form can develop later in childhood or adulthood.
Sources
Last updated 5/8/2026, 6:28:50 AM