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SAT1 (gene)

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SAT1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSAT1, DC21, KFSD, KFSDX, SAT, SSAT, SSAT-1, spermidine/spermine N1-acetyltransferase 1
External IDsOMIM: 313020; MGI: 98233; HomoloGene: 37716; GeneCards: SAT1; OMA:SAT1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

6303

20229

Ensembl

n/a

ENSMUSG00000025283

UniProt

P21673

P48026

RefSeq (mRNA)

NM_002970

NM_001291865
NM_009121

RefSeq (protein)

NP_002961

NP_001278794
NP_033147

Location (UCSC)n/aChr X: 154 – 154 Mb
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

Diamine acetyltransferase 1 is an enzyme that in humans is encoded by the SAT1 gene found on the X chromosome.[4][5][6]

Function

Spermidine/spermine N(1)-acetyltransferase (SPD/SPM acetyltransferase) is a rate-limiting enzyme in the catabolic pathway of polyamine metabolism. It catalyzes the N(1)-acetylation of spermidine and spermine and, by the successive activity of polyamine oxidase, spermine can be converted to spermidine and spermidine to putrescine.[6] The SAT1 gene is used to help regulate polymamies levels inside the cell by regulating their transport in and out of the cell.[7][8] SAT1 is also involved in the first step to synthesize N-acetylputrescine from putrescine.[9] PMF1 and NRF2 work together to transcript the SAT1 gene.[10]

Structure

The SAT1 gene is 3,069 base pairs long. There are 171 amino acids and its molecular mass is 20024 Da Daltons). In 1992 at The Johns Hopkins University School of Medicine, Lei Xiao and several others cloned over 4000 base pairs of the region containing the coding sequence of the SAT1 gene also referred to as SSAT-1, SSAT,SAT,KFSD,DC21, KFSDX gene.[11] This gene is located on the X chromosome in the region Xp22.1. The primer extension analysis indicated that the transcription started 179 bases upstream from the translational start site. Furthermore, they determined that it appeared to be controlled by a "TATA-less" promoter. Normally, there would be a TATA box where RNA polymerase II would be involved in assisting with initiation by properly positioning the enzyme, however in a TATA-less promoter situation the TATA box is absent.[12]

Clinical significance

An association with keratosis follicularis spinulosa decalvans (KFSD) has been suggested.[13] Data shows that keratosis follicularis spinulosa decalvans could be caused by mutations in the SAT 1 gene. KSFD is also believed to be X-linked, which helps prove that the disease is caused by a mutation found in the SAT 1 gene which is located on the X chromosome.[14] The mutation most likely occurs at the location Xp22.1.[15] KDSF mostly affects men, which makes sense for it to be an X-linked disease, caused by a mutation of the SAT1 gene.[16]

Elevated levels of RNA transcripts of SAT1 in the bloodstream have been associated with a higher risk of suicide.[17][18][19]

The SAT1 gene has implications with NLS-2 Neu-Laxova syndrome, type 2 (NLS). It is inherited as an autosomal recessive trait and is considered a rare lethal congenital disorder. Severe growth delays before birth including low birth weight and shorter than normal length occur. After birth, outward observable characteristics include significant small skull size (microcephaly), wider than normal spaced eyes, sloped forehead and other disfiguring facial features. There may also be random places of fluid retention (edema) throughout the body and permanent joint limitations due to limb malformations. NLS can be detected in pregnant woman with ultrasound examination. In some people of Neu-Laxova syndrome, other areas were severely affected such as skin, genitals, and other internal organs including the heart. Males and females are equally affected and could be most closely associated with persons of Pakistani origin. However, there have been cases reported in several other diverse backgrounds. The prognosis is extremely poor and in most cases the infant dies shortly after birth or are stillborn. The first documented and reported case in Japan involved a baby girl exhibiting microcephaly, severe edema, and other symptoms. In her case she had a condition known as congenital vertical talus or rocker-feet. The foot is abnormally shaped in a convex position. She survived 134 days.[20][21][22]

The SAT1 gene plays a vital role in the catabolic pathway of polyamine metabolism. It acts as a rate-limiting enzyme in the pathway of polyamine metabolism, meaning it is significant in the involvement of cell survival. Research has shown that the tumor protein known as p53 can specifically target the SAT1 gene that results in ferroptotic cell-death. Ferroptosis is when a death of a cell is caused by an iron-dependent accumulation of a lipid.[23]

References

  1. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025283 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ Casero RA, Celano P, Ervin SJ, Applegren NB, Wiest L, Pegg AE (January 1991). "Isolation and characterization of a cDNA clone that codes for human spermidine/spermine N1-acetyltransferase". The Journal of Biological Chemistry. 266 (2): 810–4. PMID 1985966.
  5. ^ Xiao L, Celano P, Mank AR, Griffin C, Jabs EW, Hawkins AL, Casero RA (September 1992). "Structure of the human spermidine/spermine N1-acetyltransferase gene (exon/intron gene organization and localization to Xp22.1)". Biochemical and Biophysical Research Communications. 187 (3): 1493–502. doi:10.1016/0006-291X(92)90471-V. PMID 1417826.
  6. ^ a b "Entrez Gene: SAT1 spermidine/spermine N1-acetyltransferase 1".
  7. ^ "SAT1 Gene". GeneCards.
  8. ^ Pegg AE (June 2008). "Spermidine/spermine-N(1)-acetyltransferase: a key metabolic regulator". American Journal of Physiology. Endocrinology and Metabolism. 294 (6): E995–1010. doi:10.1152/ajpendo.90217.2008. PMID 18349109.
  9. ^ Universal protein resource accession number P21673 for "SAT1 - Diamine acetyltransferase 1 - Homo sapiens (Human)" at UniProt.
  10. ^ Online Mendelian Inheritance in Man (OMIM): Spermidine/spermine n(1)-acetyltransferase 1; SAT1 - 313020
  11. ^ Wang, C.; Ruan, P.; Zhao, Y.; Li, X.; Wang, J.; Wu, X.; Liu, T.; Wang, S.; Hou, J.; Li, W.; Li, Q.; Li, J.; Dai, F.; Fang, D.; Wang, C.; Xie, S. (2017). "Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasis via AKT/β-catenin signaling pathways in hepatocellular and colorectal carcinoma cells". Oncotarget. 8 (1): 1092–1109. doi:10.18632/oncotarget.13582. PMC 5352037. PMID 27901475.
  12. ^ "Neu Laxova Syndrome". GARD Genetic and Rare diseases Information Center. Retrieved 19 November 2018.
  13. ^ Gimelli G, Giglio S, Zuffardi O, Alhonen L, Suppola S, Cusano R, Lo Nigro C, Gatti R, Ravazzolo R, Seri M (September 2002). "Gene dosage of the spermidine/spermine N(1)-acetyltransferase ( SSAT) gene with putrescine accumulation in a patient with a Xp21.1p22.12 duplication and keratosis follicularis spinulosa decalvans (KFSD)". Human Genetics. 111 (3): 235–41. doi:10.1007/s00439-002-0791-6. PMID 12215835.
  14. ^ "Keratosis follicularis spinulosa decalvans". Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Retrieved 2018-11-16.
  15. ^ "Keratosis Follicularis Spinulosa Decalvans, X-Linked". Hereditary Ocular Diseases. Retrieved 2018-11-16.
  16. ^ "SAT1 gene". Genetics Home Reference. Retrieved 17 November 2018.
  17. ^ Honor Whiteman (21 August 2013). "'Biological signal' of suicide risk found in blood". Medical News Today. Retrieved 21 August 2013.
  18. ^ Le-Niculescu H, Levey DF, Ayalew M, Palmer L, Gavrin LM, Jain N, Winiger E, Bhosrekar S, Shankar G, Radel M, Bellanger E, Duckworth H, Olesek K, Vergo J, Schweitzer R, Yard M, Ballew A, Shekhar A, Sandusky GE, Schork NJ, Kurian SM, Salomon DR, Niculescu AB (December 2013). "Discovery and validation of blood biomarkers for suicidality". Molecular Psychiatry. 18 (12): 1249–64. doi:10.1038/mp.2013.95. PMC 3835939. PMID 23958961.
  19. ^ Le-Niculescu H, Levey DF, Ayalew M, Palmer L, Gavrin LM, Jain N, et al. (December 2013). "Discovery and validation of blood biomarkers for suicidality". Molecular Psychiatry. 18 (12): 1249–64. doi:10.1038/mp.2013.95. PMC 3835939. PMID 23958961. {{cite journal}}: Unknown parameter |lay-source= ignored (help); Unknown parameter |lay-url= ignored (help)
  20. ^ Hirota T, Hirota Y, Asagami C, Muto M (March 1998). "A Japanese case of Neu-Laxova syndrome". The Journal of Dermatology. 25 (3): 163–6. doi:10.1111/j.1346-8138.1998.tb02373.x. PMID 9575678.
  21. ^ Barekatain B, Sadeghnia A, Rouhani E, Soofi GJ (2018). "A New Case of Neu-Laxova Syndrome: Infant with Facial Dysmorphism, Arthrogryposis, Ichthyosis, and Microcephalia". Advanced Biomedical Research. 7: 68. doi:10.4103/abr.abr_143_17. PMC 5952546. PMID 29862217.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  22. ^ Amini E, Azadi N, Sheikh M (March 2017). "New Insights on Genetic Features of Neu-Laxova Syndrome". Iranian Journal of Neonatology IJN. 8 (1): 40–2.
  23. ^ Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, et al. (October 2017). "Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease". Cell. 171 (2): 273–285. doi:10.1016/j.cell.2017.09.021. PMC 5685180. PMID 28985560.

Further reading

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