UniProt: P21673 (SAT1_HUMAN). Gene: SAT1 (HGNC:10540), synonym SAT, SSAT, SSAT-1.
171 aa, ~20 kDa, cytosolic. Chromosome Xp22.1. EC 2.3.1.57.
SAT1/SSAT1 is the rate-limiting enzyme of polyamine catabolism / back-conversion.
It is a cytosolic, acetyl-CoA–dependent GNAT-family (GCN5-related) N-acetyltransferase
that N1-acetylates the polyamines spermine and spermidine (and related diamines),
producing N1-acetylspermine / N1-acetylspermidine + CoA. The N1-acetylated products are
then either exported from the cell or oxidized by acetylpolyamine oxidase (PAOX), driving
back-conversion spermine → spermidine → putrescine.
PMID:1985966 (Casero et al. 1991, cDNA cloning of human SSAT1): "Spermidine/spermine
N1-acetyltransferase (Spd/Spm acetyltransferase) is the rate-limiting enzyme in the
catabolism of polyamines. This enzyme is highly inducible by several stimuli, including
the natural polyamines and their structural analogues." This is the original SAT1 cDNA
characterization and the source of the TAS diamine-N-acetyltransferase annotation. Highly
relevant, verified. PMID:1985966
PMID:16455797 (Bewley et al. 2006, PNAS, crystal structures): "Spermidine/spermine
N1-acetyltransferase (SSAT) is a key enzyme in the control of polyamine levels in human
cells, as acetylation of spermidine and spermine triggers export or degradation." WT and
mutant human SSAT structures with CoA/AcCoA/spermine/inhibitor; homodimer; Y140F mutant
reduces activity ~95%. Also reports self-acetylation of Lys26. Directly establishes the
catalytic MF and homodimer. Source of the EXP diamine-N-acetyltransferase annotation and
IPI identical-protein-binding (homodimer). PMID:16455797;
PMID:16455797.
PMID:17516632 (Hegde et al. 2007, Biochemistry, mechanism + structure): "The
N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT)
is a crucial step in the regulation of the cellular polyamine levels in eukaryotic cells."
Random sequential kinetic mechanism; ternary complex; Tyr140 general acid, Glu92 general
base; pH-activity bell-shaped. Source of the second EXP diamine-N-acetyltransferase
annotation and the definitive kinetic/mechanistic characterization.
PMID:17516632;
PMID:17516632.
PMID:15283699 (Coleman et al. 2004, Biochem J). IMPORTANT: the paper's primary
subject is SSAT2 (SAT2, a paralog), and it concludes SSAT2 is NOT a polyamine catabolic
enzyme. SSAT1 (this gene, P21673) is used throughout as the well-characterized comparator:
"Spermidine/spermine-N1-acetyltransferase (SSAT1) is a short-lived polyamine catabolic
enzyme inducible by polyamines and polyamine analogues"; "Induction of SSAT1 plays an
important role in polyamine homoeostasis, since the N1-acetylated polyamines can be
excreted or oxidized by acetylpolyamine oxidase." UniProt cites this PMID as EXP evidence
for SAT1 catalytic activity (KM/kcat for spermine/spermidine measured on SSAT1). The GOA
IDA annotations from this paper to SAT1 are therefore defensible for MF (diamine/
N-acetyltransferase activity) — the full text characterizes SSAT1 activity as the reference
standard. However the IDA to GO:0006596 polyamine BIOSYNTHETIC process is wrong-direction
(SSAT1 is catabolic, not biosynthetic) — MODIFY to polyamine catabolic process.
PMID:15283699; PMID:15283699; PMID:15283699.
PMID:11866539 (Aitkenhead et al. 2002, Microvasc Res): in-vitro angiogenesis model
(EC tube formation in 3D collagen); representational difference analysis identified genes
upregulated in tube-forming cells. SAT1 appears among the ~2- to 10-fold upregulated genes.
This is an IEP expression-correlation annotation to GO:0001525 angiogenesis. The abstract
foregrounds ESM-1/βig-h3/NrCAM; SAT1 is a co-identified upregulated transcript, not shown
to have a causal angiogenic function. Keep as non-core (expression association, not the
enzyme's evolved role). PMID:11866539.
Reactome R-HSA-351200 "Interconversion of polyamines", R-HSA-351207 "Spermine =>
N-acetylated spermine", R-HSA-351208 "Spermidine => N-acetylated spermidine": model
SAT1 as the cytosolic SSAT catalyzing the rate-limiting N1-acetylation step of polyamine
back-conversion; the acetylated intermediates are oxidized by PAOX/SMOX. These support the
TAS diamine-N-acetyltransferase MF and cytosol location. NOTE: GOA maps R-HSA-351200 to
GO:0006596 polyamine biosynthetic process, which mislabels the interconversion pathway;
the pathway is back-conversion (catabolic). MODIFY the BP to polyamine catabolic process.
The many GO:0005515 "protein binding" IPI annotations (PMID:16169070, 16189514, 19060904,
21516116, 25416956, 29892012, 31515488, 32296183, 32814053, 33961781) derive from
high-throughput yeast-two-hybrid / interactome and AP-MS proteome-scale screens (IntAct).
The partner lists are large, promiscuous, and non-overlapping across screens (APP, CASP7,
KCNA4, HOXB9, TCF25, PSMA1, etc.), with no coherent biological complex. These are
uninformative "protein binding" annotations — mark as over-annotated (not core), but per
policy do NOT remove experimental IPI. Bare "protein binding" is not used in core_functions.
The GO:0042802 "identical protein binding" IPI annotations (PMID:16189514 Y2H self-hit;
PMID:16455797 crystallographic homodimer; PMID:25416956 interactome self-hit) are supported
by the biologically real homodimer (UniProt SUBUNIT "Homodimer"; PubMed:16455797, 16544326,
17516632). These are ACCEPT — homodimerization is a genuine, structurally validated property.