Argininosuccinate synthetase 1

Argininosuccinate synthetase is an enzyme that in humans is encoded by the ASS1 gene.^[5][6][7]

ASS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2NZ2
Identifiers
Aliases	ASS1, ASS, CTLN1, Argininosuccinate synthetase 1, argininosuccinate synthase 1
External IDs	OMIM: 603470; MGI: 88090; HomoloGene: 6899; GeneCards: ASS1; OMA:ASS1 - orthologs
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q34.11 Start 130,444,961 bp[1] End 130,501,274 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 B|2 21.81 cM Start 31,360,219 bp[2] End 31,410,684 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver palpebral conjunctiva kidney tubule glomerulus metanephric glomerulus corpus epididymis adipose tissue rectum human kidney mucosa of transverse colon Top expressed in human kidney right kidney hepatobiliary system exocrine gland liver renal cortex proximal tubule yolk sac placenta blastocyst More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding amino acid binding ligase activity protein binding identical protein binding ATP binding argininosuccinate synthase activity RNA binding toxic substance binding Cellular component extracellular exosome mitochondrion myelin sheath cytoplasm cytosol nucleus mitochondrial outer membrane lysosome endoplasmic reticulum neuron projection soma perikaryon cell body fiber Biological process aspartate metabolic process cellular response to laminar fluid shear stress urea cycle positive regulation of nitric oxide biosynthetic process negative regulation of leukocyte cell-cell adhesion cellular amino acid biosynthetic process citrulline metabolic process argininosuccinate metabolic process arginine biosynthetic process kidney development liver development acute-phase response midgut development ageing response to nutrient circadian rhythm response to toxic substance response to zinc ion response to mycotoxin response to amine response to estradiol response to lipopolysaccharide response to amino acid response to peptide hormone response to steroid hormone response to glucocorticoid response to growth hormone diaphragm development response to fatty acid cellular response to lipopolysaccharide cellular response to amino acid stimulus cellular response to ammonium ion cellular response to cAMP cellular response to interferon-gamma cellular response to tumor necrosis factor cellular response to glucagon stimulus cellular response to oleic acid cellular response to amine stimulus cellular response to dexamethasone stimulus Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 445 11898 Ensembl ENSG00000130707 ENSMUSG00000076441 UniProt P00966 P16460 RefSeq (mRNA) NM_000050 NM_054012 NM_007494 RefSeq (protein) NP_000041 NP_446464 NP_031520 Location (UCSC) Chr 9: 130.44 – 130.5 Mb Chr 2: 31.36 – 31.41 Mb PubMed search [3] [4]
Wikidata
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The protein encoded by this gene catalyzes the penultimate step of the arginine biosynthetic pathway. There are approximately 10 to 14 copies of this gene including the pseudogenes scattered across the human genome, among which the one located on chromosome 9 appears to be the only functional gene for argininosuccinate synthetase. Two transcript variants encoding the same protein have been found for this gene.^[7]

Clinical significance

Mutations in the chromosome 9 copy of ASS cause citrullinemia.^[5]

Arginine is considered a non-essential amino acid since normal cells can synthesize it from citrulline and aspartate using the enzymes argininosuccinate synthase 1 (ASS1) and argininosuccinate lyase (ASL). Consequently, depleting arginine can be an effective therapeutic approach. Notably, over 70% of tumors show reduced ASS1 transcription, making these cancer cells reliant on external sources of arginine, which forms the basis of arginine-deprivation therapy.^[8]

The investigational drug pegargiminase that degrades arginine is currently in trials for the treatment of ASS1 deficient cancers.^[9]