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SPERMIDINE/SPERMINE N(1)-ACETYLTRANSFERASE 2; SAT2

SPERMIDINE/SPERMINE N(1)-ACETYLTRANSFERASE 2; SAT2

Alternative titles; symbolsSSAT2THIALYSINE N-EPSILON-ACETYLTRANSFERASEHGNC Approved Gene Symbol: SAT2Cytogenetic location: 17p13.1 Genomic coordinates (GRCh3...

Alternative titles; symbols

  • SSAT2
  • THIALYSINE N-EPSILON-ACETYLTRANSFERASE

HGNC Approved Gene Symbol: SAT2

Cytogenetic location: 17p13.1 Genomic coordinates (GRCh38): 17:7,626,233-7,627,877 (from NCBI)

▼ Cloning and Expression
In the polyamine back-conversion pathway, spermidine/spermine N(1)-acetyltransferase-1 (SAT1; 313020) acetylates spermine and spermidine, which are then oxidized by polyamine oxidase to produce spermidine and putrescine, respectively. By database analysis to search for genes similar to SAT1, Chen et al. (2003) identified SAT2, which they called SSAT2. The deduced 170-amino acid protein has a calculated molecular mass of 19 kD and has 46% amino acid identity to SAT1. Both SAT1 and SAT2 contain a general N(1)-acetyltransferase (GNAT) domain spanning 87 amino acids. SAT2 homologs were found in a variety of species from bacteria to eukaryotes in all major lineages. All species below vertebrates had 1 copy of SSAT, whereas all vertebrate species, with the exception of chicken and Xenopus, had functional SAT1 and SAT2 genes. Northern blot and EST analysis indicated that SAT1 was expressed at higher levels than SAT2 and in a wider range of tissues, although bone, cervix, ovary, and pineal gland expressed only SAT2.

By searching an EST database for sequences similar to SSAT1, followed by PCR of fetal liver and HeLa cell cDNA libraries, Coleman et al. (2004) cloned SSAT2. They also identified a SSAT2 splice variant lacking exon 4. Both S. pombe and human SSAT2 lack C-terminal residues that in SSAT1 are important for polyamine acetyltransferase activity and for SSAT1 proteolytic degradation. PCR analysis revealed ubiquitous expression of 2 SSAT2 variants in human tissues.

▼ Gene Function
Chen et al. (2003) found that SAT1 showed a much greater preference for spermidine than spermine, whereas SAT2 showed similar preference for the 2 polyamines. Both SAT1- and SAT2-transfected cell extracts had much higher acetylating activity than vector-transfected cell extracts; however, SAT2 had no effect on polyamine pools in intact transfected cells. They concluded that SAT2 is probably contained within an organelle that prevents interaction with intracellular polyamines and/or with the enzyme cofactor acetyl-CoA. Unlike SAT1, SAT2 was not inducible by spermine analogs at the level of mRNA or enzyme activity.

Coleman et al. (2004) found that polyamines were poor acetyl acceptors in reactions catalyzed by purified recombinant S. pombe or human SSAT2. Thialysine, a naturally occurring modified amino acid, was a much better substrate for SSAT2, but not for SSAT1, and was acetylated by SSAT2 at the epsilon-amino group. Human SSAT2 also acetylated L-lysine, but much less efficiently. In contrast to SSAT1, SSAT2 was not toxic when overexpressed in mouse fibroblasts, it had little effect on the polyamine content of transfected cells, and its expression was unaffected by treatment with a polyamine analog. In addition, unlike SSAT1, SSAT2 was relatively stable in in vitro stability assays and in transfected cells. Coleman et al. (2004) concluded that SSAT2 is not involved in polyamine metabolism and suggested that it should be renamed 'thialysine N-epsilon-acetyltransferase.'

The HIF1 complex is a heterodimeric transcription factor that functions in oxygen homeostasis. The HIF1A subunit (603348) is subject to oxygen-dependent prolyl hydroxylation leading to ubiquitination by the VHL (608537)-elongin C (TCEB1; 600788) ubiquitin-ligase complex, followed by degradation of HIF1A by the 26S proteasome (see 602706). Using gain- and loss-of-function experiments, Baek et al. (2007) found that SSAT2 played an essential role in this process. SSAT2 bound HIF1A, VHL, and elongin C and promoted ubiquitination of hydroxylated HIF1A by stabilizing the interaction of VHL and elongin C. Regulation of HIF1A by SSAT2 depended upon prolyl hydroxylation of HIF1A by PHD2 (EGLN1; 606425). Mutation of the conserved SSAT2 residues ser82 and thr83, which are required for acetyltransferase activity, reduced, but did not eliminate, the ability of SSAT2 to promote HIF1A degradation.

▼ Gene Structure
Chen et al. (2003) determined that the SAT2 gene contains 6 exons.

▼ Mapping
Chen et al. (2003) stated that the SAT2 gene maps to chromosome 17p13.1.

Tags: 17p13.1