Argininosuccinate synthetase 1

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

ASS1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesASS1, ASS, CTLN1, Argininosuccinate synthetase 1, argininosuccinate synthase 1
External IDsOMIM: 603470; MGI: 88090; HomoloGene: 6899; GeneCards: ASS1; OMA:ASS1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000050
NM_054012

NM_007494

RefSeq (protein)

NP_000041
NP_446464

NP_031520

Location (UCSC)Chr 9: 130.44 – 130.5 MbChr 2: 31.36 – 31.41 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000130707Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000076441Ensembl, 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. ^ a b 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. ^ a b "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

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Further reading

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  • 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.
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