Argininosuccinate synthetase 1

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 kidney glomerulus metanephric glomerulus corpus epididymis adipose tissue rectum abdominal fat Top expressed in kidney hepatobiliary system exocrine gland liver renal cortex proximal tubule yolk sac placenta blastocyst lens 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 neuronal cell body 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 human 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
View/Edit Human View/Edit Mouse

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

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]

References

1. GRCh38: Ensembl release 89: ENSG00000130707 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000076441 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Beaudet AL, O'Brien WE, Bock HG, Freytag SO, Su TS (Mar 1986). "The Human Argininosuccinate Synthetase Locus and Citrullinemia". Advances in Human Genetics 15. Vol. 15. pp. 161–96, 291–2. doi:10.1007/978-1-4615-8356-1_3. ISBN   978-1-4615-8358-5. PMID   3513483.
6. Carritt B, Goldfarb PS, Hooper ML, Slack C (April 1977). "Chromosome assignment of a human gene for argininosuccinate synthetase expression in Chinese hamsterxhuman somatic cell hybrids". Experimental Cell Research. 106 (1): 71–78. doi:10.1016/0014-4827(77)90242-7. PMID   852520.
7. "Entrez Gene: ASS1 argininosuccinate synthetase 1".
8. Chen CL, Hsu SC, Ann DK, Yen Y, Kung HJ (July 2021). "Arginine Signaling and Cancer Metabolism". Cancers. 13 (14): 3541. doi: 10.3390/cancers13143541 . PMC   8306961 . PMID   34298755.
9. Field GC, Pavlyk I, Szlosarek PW (February 2023). "Bench-to-Bedside Studies of Arginine Deprivation in Cancer". Molecules. 28 (5). Basel, Switzerland: 2150. doi: 10.3390/molecules28052150 . PMC   10005060 . PMID   36903394.

Further reading

• Ikeda S (December 2000). "[Recent advances of the treatment in metabolic disorders]". Rinsho Shinkeigaku = Clinical Neurology. 40 (12): 1264–1266. PMID   11464474.
• Carritt B (1977). "Somatic cell genetic evidence for the presence of a gene for citrullinemia on human chromosome 9". Cytogenetics and Cell Genetics. 19 (1): 44–48. doi:10.1159/000130793. PMID   891260.
• Dhanakoti SN, Brosnan ME, Herzberg GR, Brosnan JT (March 1992). "Cellular and subcellular localization of enzymes of arginine metabolism in rat kidney". The Biochemical Journal. 282 ( Pt 2) (Pt 2): 369–375. doi:10.1042/bj2820369. PMC   1130788 . PMID   1312326.
• Wakui H, Komatsuda A, Itoh H, Kobayashi R, Nakamoto Y, Miura AB (1992). "Renal argininosuccinate synthetase: purification, immunohistochemical localization, and elastin-binding property". Renal Physiology and Biochemistry. 15 (1): 1–9. doi:10.1159/000173435. PMID   1372742.
• Kobayashi K, Rosenbloom C, Beaudet AL, O'Brien WE (February 1991). "Additional mutations in argininosuccinate synthetase causing citrullinemia". Molecular Biology & Medicine. 8 (1): 95–100. PMID   1943692.
• Kobayashi K, Jackson MJ, Tick DB, O'Brien WE, Beaudet AL (July 1990). "Heterogeneity of mutations in argininosuccinate synthetase causing human citrullinemia". The Journal of Biological Chemistry. 265 (19): 11361–11367. doi: 10.1016/S0021-9258(19)38601-6 . PMID   2358466.
• Isashiki Y, Noda T, Kobayashi K, Sase M, Saheki T, Titani K (July 1989). "Identification of essential arginine residue(s) for Mg-ATP binding of human argininosuccinate synthetase". Protein Sequences & Data Analysis. 2 (4): 283–287. PMID   2788888.
• Jinno Y, Nomiyama H, Matuo S, Shimada K, Matsuda I, Saheki T (1987). "Structure of the 5' end region of the human argininosuccinate synthetase gene". Journal of Inherited Metabolic Disease. 8 (3): 157–159. doi:10.1007/BF01819307. PMID   3027451. S2CID   32917363.
• Freytag SO, Beaudet AL, Bock HG, O'Brien WE (October 1984). "Molecular structure of the human argininosuccinate synthetase gene: occurrence of alternative mRNA splicing". Molecular and Cellular Biology. 4 (10): 1978–1984. doi:10.1128/mcb.4.10.1978. PMC   369014 . PMID   6095035.
• Bock HG, Su TS, O'Brien WE, Beaudet AL (September 1983). "Sequence for human argininosuccinate synthetase cDNA". Nucleic Acids Research. 11 (18): 6505–6512. doi:10.1093/nar/11.18.6505. PMC   326390 . PMID   6194510.
• Freytag SO, Bock HG, Beaudet AL, O'Brien WE (March 1984). "Molecular structures of human argininosuccinate synthetase pseudogenes. Evolutionary and mechanistic implications". The Journal of Biological Chemistry. 259 (5): 3160–3166. doi: 10.1016/S0021-9258(17)43275-3 . PMID   6321498.
• Kobayashi K, Kakinoki H, Fukushige T, Shaheen N, Terazono H, Saheki T (October 1995). "Nature and frequency of mutations in the argininosuccinate synthetase gene that cause classical citrullinemia". Human Genetics. 96 (4): 454–463. doi:10.1007/BF00191806. PMID   7557970. S2CID   861085.
• Kobayashi K, Shaheen N, Terazono H, Saheki T (December 1994). "Mutations in argininosuccinate synthetase mRNA of Japanese patients, causing classical citrullinemia". American Journal of Human Genetics. 55 (6): 1103–1112. PMC   1918437 . PMID   7977368.
• Shaheen N, Kobayashi K, Terazono H, Fukushige T, Horiuchi M, Saheki T (1996). "Characterization of human wild-type and mutant argininosuccinate synthetase proteins expressed in bacterial cells". Enzyme & Protein. 48 (5–6): 251–264. doi:10.1159/000474998. PMID   8792870.
• Gress TM, Müller-Pillasch F, Geng M, Zimmerhackl F, Zehetner G, Friess H, et al. (October 1996). "A pancreatic cancer-specific expression profile". Oncogene. 13 (8): 1819–1830. PMID   8895530.
• Ji H, Reid GE, Moritz RL, Eddes JS, Burgess AW, Simpson RJ (1997). "A two-dimensional gel database of human colon carcinoma proteins". Electrophoresis. 18 (3–4): 605–613. doi:10.1002/elps.1150180344. PMID   9150948. S2CID   25454450.

Further reading

• Mew A, Simpson KL, Gropman AL, Lanpher BC, Chapman KA, Summar ML (22 June 2017). "Urea Cycle Disorders Overview". In Adam MP, Feldman J, Mirzaa GM, et al. (eds.). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle.
• Quinonez SC, Lee KN (18 August 2022). "Citrullinemia Type I". In Adam MP, Feldman J, Mirzaa GM, et al. (eds.). GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle.

External links

• Human ASS1 genome location and ASS1 gene details page in the UCSC Genome Browser .