SAT1 (diamine acetyltransferase 1; spermidine/spermine N1-acetyltransferase, SSAT1) is a cytosolic, acetyl-CoA-dependent N-acetyltransferase of the GNAT (GCN5-related N-acetyltransferase) superfamily and the rate-limiting enzyme of polyamine catabolism (back-conversion). It catalyzes the N1-acetylation of the higher polyamines spermine and spermidine (and related alkane-alpha,omega-diamines) using acetyl-CoA, producing N1-acetylspermine or N1-acetylspermidine plus CoA (EC 2.3.1.57). The N1-acetylated polyamines are then either exported from the cell or oxidized by acetylpolyamine oxidase (PAOX), driving the interconversion spermine -> spermidine -> putrescine. SAT1 is a short-lived, highly inducible enzyme (induced by polyamines and their analogues, and by diverse stresses) and thereby provides fine control of intracellular polyamine concentrations and polyamine efflux. The enzyme is a homodimer of ~171-residue, ~20 kDa subunits; catalysis proceeds through a ternary complex with an active-site tyrosine (Tyr140) acting as the general acid. It is broadly expressed and acts in the cytosol.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004145 diamine N-acetyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) inference of diamine N-acetyltransferase activity, the core, evolutionarily conserved molecular function of SAT1/SSAT1. This is directly and experimentally confirmed for the human protein (EC 2.3.1.57; crystal structures with acetyl-CoA and spermine; kinetic mechanism). Accept as a core molecular function. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Enzyme which catalyzes the acetylation of polyamines |
| GO:0019809 spermidine binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) inference that SAT1 binds spermidine. Spermidine is a bona fide substrate (spermidine + acetyl-CoA = N1-acetylspermidine + CoA), so substrate binding is real, but as a stand-alone molecular-function annotation it is subsumed by the catalytic diamine N-acetyltransferase activity and is not independently informative of the enzyme's core function. Keep as non-core. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Enzyme which catalyzes the acetylation of polyamines |
| GO:0004145 diamine N-acetyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (IEA) assignment of diamine N-acetyltransferase activity via ARBA/Rhea/EC mapping (RHEA:11116, RHEA:28150, EC:2.3.1.57). This is the correct catalytic activity and matches the experimentally verified EC number in UniProt. Accept as a core molecular function. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Enzyme which catalyzes the acetylation of polyamines |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic (IEA) subcellular-location mapping to cytosol, consistent with the UniProt curated location and with the enzyme's role in cytosolic polyamine acetylation. Accept as the core localization. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Cytoplasm, cytosol |
| GO:0006595 polyamine metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Electronic (ARBA) assignment to the general parent term polyamine metabolic process. Correct but non-specific: SAT1 acts specifically in polyamine catabolism/back-conversion. Keep as a (broad) non-core annotation; the more specific catabolic terms capture the core biological role. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Enzyme which catalyzes the acetylation of polyamines |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Electronic (InterPro2GO, from the GNAT/acetyl-CoA acyltransferase domain IPR000182) assignment of a general acyltransferase activity. This is a correct but very broad grouping term; the specific activity (diamine N-acetyltransferase, GO:0004145) is better and is separately annotated. Keep as non-core. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Enzyme which catalyzes the acetylation of polyamines |
| GO:0005515 protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a high-throughput protein-interaction dataset (IntAct; partner KCNA4). Uninformative regarding the enzyme's function and not part of a coherent biological complex. Retain the experimental IPI but mark as over-annotated; not a core function. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a proteome-scale binary yeast-two-hybrid interactome map (CCSB-HI1). Uninformative regarding molecular function. Retain the experimental IPI but mark as over-annotated; not a core function. |
| GO:0005515 protein binding | IPI PMID:19060904 An empirical framework for binary interactome mapping. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a high-throughput binary interactome mapping study. Uninformative for function. Retain the experimental IPI but mark as over-annotated. |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a next-generation-sequencing interactome dataset. Uninformative for function. Retain the experimental IPI but mark as over-annotated. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a proteome-scale human interactome map (many heterogeneous partners). Uninformative for function. Retain the experimental IPI but mark as over-annotated. |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from an interactome-perturbation screen. Uninformative for function. Retain the experimental IPI but mark as over-annotated. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a variant-interactome disruption study. Uninformative for function. Retain the experimental IPI but mark as over-annotated. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a reference binary-interactome map (HuRI; large, heterogeneous partner list). Uninformative for function. Retain the experimental IPI but mark as over-annotated. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a neurodegenerative-disease interactome study (partner APP). Uninformative for the enzyme's core function. Retain the experimental IPI but mark as over-annotated. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a cell-specific dual proteome-scale interactome (BioPlex). Uninformative for function. Retain the experimental IPI but mark as over-annotated. |
| GO:0042802 identical protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | ACCEPT | Summary: Self-interaction (identical protein binding) detected by yeast-two-hybrid. This is consistent with the biologically real, structurally validated SAT1 homodimer, so the annotation is meaningful. Accept. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Homodimer |
| GO:0042802 identical protein binding | IPI PMID:16455797 Structures of wild-type and mutant human spermidine/spermine... | ACCEPT | Summary: Identical protein binding supported by high-resolution crystal structures showing SAT1 is a homodimer, with each active site formed at the subunit interface. This is a genuine, functionally relevant property of the enzyme. Accept. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Homodimer PMID:16455797 a key enzyme in the control |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | ACCEPT | Summary: Self-interaction from a proteome-scale interactome map, consistent with the validated SAT1 homodimer. Accept. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Homodimer |
| GO:0006596 polyamine biosynthetic process | TAS Reactome:R-HSA-351200 | MODIFY | Summary: This TAS annotation comes from the Reactome "Interconversion of polyamines" pathway, which describes back-conversion (spermine -> spermidine -> putrescine) via SAT1-mediated N1-acetylation followed by oxidation. That is a catabolic/interconversion process, not biosynthesis; the mapping to polyamine BIOSYNTHETIC process is the wrong pathway direction. Modify to polyamine catabolic process. Proposed replacements: polyamine catabolic process Supporting Evidence: Reactome:R-HSA-351200 These events require the formation of N-acetylated intermediates, N1-acetylspermine and N1-acetylspermidine catalyzed by a cytosolic acetyl-CoA:spermidine/spermine N1-acetyl-tranferase (SSAT) enzyme. |
| GO:0009447 putrescine catabolic process | IEA GO_REF:0000041 | KEEP AS NON CORE | Summary: Electronic (UniPathway UPA00188) assignment to putrescine catabolic process, reflecting the UniProt PATHWAY "putrescine degradation; N-acetylputrescine from putrescine". SAT1 does N-acetylate diamines including 1,4-diaminobutane (putrescine), so this is a legitimate part of its diamine-acetyltransferase activity, though the physiologically dominant substrates are spermidine and spermine. Keep as a non-core catabolic role. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Enzyme which catalyzes the acetylation of polyamines |
| GO:0004145 diamine N-acetyltransferase activity | TAS Reactome:R-HSA-351207 | ACCEPT | Summary: TAS annotation (Reactome "Spermine => N-acetylated spermine") of the core catalytic activity: SAT1 acetylates spermine to N-acetylspermine, the rate-limiting step of polyamine catabolism. Accept as a core molecular function. Supporting Evidence: Reactome:R-HSA-351207 Spermidine/spermine N1-acetyltransferase (SAT1, also known as diamine acetyltransferase 1) acetylates spermine (SPN) to yield N-acetylspermine (NASPN). |
| GO:0004145 diamine N-acetyltransferase activity | TAS Reactome:R-HSA-351208 | ACCEPT | Summary: TAS annotation (Reactome "Spermidine => N-acetylated spermidine") of the core catalytic activity: SAT1 acetylates spermidine to N-acetylspermidine. Accept as a core molecular function. Supporting Evidence: Reactome:R-HSA-351208 Spermidine/spermine N1-acetyltransferase (SAT1, also known as diamine acetyltransferase 1) acetylates spermidine (SPM) to yield N-acetylspermidine (NASPM). |
| GO:0004145 diamine N-acetyltransferase activity | EXP PMID:16455797 Structures of wild-type and mutant human spermidine/spermine... | ACCEPT | Summary: Experimental (structural/enzymatic) evidence for diamine N-acetyltransferase activity: high-resolution structures of human SSAT with acetyl-CoA, spermine and inhibitor, plus the Y140F mutant showing ~95% loss of activity, directly establish the catalytic MF. Accept as a core molecular function. Supporting Evidence: PMID:16455797 a key enzyme in the control |
| GO:0004145 diamine N-acetyltransferase activity | EXP PMID:17516632 Mechanistic and structural analysis of human spermidine/sper... | ACCEPT | Summary: Experimental (kinetic and structural) evidence for diamine N-acetyltransferase activity: steady-state kinetics, a random sequential mechanism, a ternary-complex structure with the bisubstrate inhibitor, and assignment of Tyr140/Glu92 as catalytic residues. Directly establishes the core catalytic MF. Accept. Supporting Evidence: PMID:17516632 The N1-acetylation of spermidine and spermine by spermidine/spermine PMID:17516632 random sequential mechanism for the enzyme |
| GO:0004145 diamine N-acetyltransferase activity | IDA PMID:15283699 Spermidine/spermine-N1-acetyltransferase-2 (SSAT2) acetylate... | ACCEPT | Summary: IDA for diamine N-acetyltransferase activity. This paper's primary subject is the paralog SSAT2, but SSAT1 (this gene, P21673) is characterized in parallel as the well-established polyamine-catabolic acetyltransferase reference standard (its KM/kcat for spermine and spermidine are reported, and UniProt cites this PMID as EXP evidence for SAT1 catalytic activity). The core MF assignment to SAT1 is correct. Accept. Supporting Evidence: PMID:15283699 inducible by polyamines and polyamine analogues file:human/SAT1/SAT1-uniprot.txt Enzyme which catalyzes the acetylation of polyamines |
| GO:0006596 polyamine biosynthetic process | IDA PMID:15283699 Spermidine/spermine-N1-acetyltransferase-2 (SSAT2) acetylate... | MODIFY | Summary: Wrong pathway direction. SSAT1 is a polyamine CATABOLIC enzyme (its N1-acetylated products are exported or oxidized, driving back-conversion/degradation), not a biosynthetic enzyme; the cited paper explicitly frames SSAT1 as a polyamine catabolic enzyme important for polyamine homeostasis. The experimental evidence is sound but the GO term is incorrect. Modify to polyamine catabolic process. Proposed replacements: polyamine catabolic process Supporting Evidence: PMID:15283699 plays an important role in polyamine homoeostasis PMID:15283699 polyamines can be excreted or oxidized by acetylpolyamine oxidase |
| GO:0008080 N-acetyltransferase activity | IDA PMID:15283699 Spermidine/spermine-N1-acetyltransferase-2 (SSAT2) acetylate... | KEEP AS NON CORE | Summary: IDA for the general parent term N-acetyltransferase activity. Correct but broad; the specific activity is diamine N-acetyltransferase (GO:0004145), which is separately and more informatively annotated. Keep as non-core. Supporting Evidence: PMID:15283699 short-lived polyamine |
| GO:0005829 cytosol | TAS Reactome:R-HSA-351207 | ACCEPT | Summary: TAS (Reactome) localization to cytosol, consistent with the curated UniProt location and the enzyme's cytosolic acetyl-CoA-dependent activity. Accept as the core localization. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Cytoplasm, cytosol |
| GO:0005829 cytosol | TAS Reactome:R-HSA-351208 | ACCEPT | Summary: TAS (Reactome) localization to cytosol, duplicate of the R-HSA-351207 call and consistent with the UniProt curated location. Accept as the core localization. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Cytoplasm, cytosol |
| GO:0001525 angiogenesis | IEP PMID:11866539 Identification of endothelial cell genes expressed in an in ... | KEEP AS NON CORE | Summary: IEP annotation based on expression: SAT1 was among genes upregulated (2- to 10-fold) in endothelial cells forming tubes in a 3D in-vitro angiogenesis model. This is an expression correlation, not evidence that SAT1's enzymatic activity drives angiogenesis; the study foregrounds ESM-1/betaig-h3/NrCAM. Keep as a non-core, context-specific expression association rather than a core evolved function. Supporting Evidence: PMID:11866539 2- to 10-fold upregulation |
| GO:0004145 diamine N-acetyltransferase activity | TAS PMID:1985966 Isolation and characterization of a cDNA clone that codes fo... | ACCEPT | Summary: TAS from the original human SSAT1 cDNA cloning paper, which established that the encoded protein is an active spermidine/spermine N1-acetyltransferase and the rate-limiting enzyme of polyamine catabolism. Accept as a core molecular function. Supporting Evidence: PMID:1985966 rate-limiting enzyme in the catabolism of polyamines |
| GO:0046203 spermidine catabolic process | IDA | NEW | Summary: Proposed more specific catabolic term. SAT1-catalyzed N1-acetylation of spermidine is the committed, rate-limiting step of spermidine back-conversion (to putrescine via N1-acetylspermidine and PAOX). Not currently in GOA (which has the broader parent), but well supported and central to the enzyme's function. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Enzyme which catalyzes the acetylation of polyamines |
| GO:0046208 spermine catabolic process | IDA | NEW | Summary: Proposed more specific catabolic term. SAT1-catalyzed N1-acetylation of spermine is the committed, rate-limiting step of spermine back-conversion (to spermidine via N1-acetylspermine and PAOX). Not currently in GOA, but well supported and central to the enzyme's function. Supporting Evidence: file:human/SAT1/SAT1-uniprot.txt Enzyme which catalyzes the acetylation of polyamines |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)