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Information on EC 2.3.1.57 - diamine N-acetyltransferase and Organism(s) Homo sapiens and UniProt Accession P21673
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2.3.1.57 diamine N-acetyltransferaseIUBMB Comments
Acts on propane-1,3-diamine, pentane-1,5-diamine, putrescine, spermidine (forming N1- and N8-acetylspermidine), spermine, N1-acetylspermidine and N8-acetylspermidine.
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Word Map
- 2.3.1.57
- polyamine
- ornithine
- s-adenosylmethionine
- n1-acetylspermidine
-
denspm
- pao
- n1,n11-diethylnorspermine
- n1,n12-bisethylspermine
- alpha-difluoromethylornithine
- analysis
-
superinduction
- antizyme
- drug development
-
malme-3m
-
n1-acetylation
-
gcn5-related
- pharmacology
-
bisguanylhydrazone
- medicine
- adometdc
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
spermidine/spermine n1-acetyltransferase, spermidine n1-acetyltransferase, ssat1, ssat2, spermidine acetyltransferase, spermidine/spermine acetyltransferase, spermidine/spermine-n1-acetyltransferase, ssat-1, spermidine n-acetyltransferase, ssatx, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
spermidine/spermine N1-acetyltransferase 1
-
acetyl-coenzyme A-1,4-diaminobutane N-acetyltransferase
-
-
-
-
acetyltransferase, putrescine
-
-
-
-
diamine acetyltransferase
-
-
-
-
N1-SAT
-
-
-
-
N1SSAT
-
-
-
-
putrescine (diamine)-acetylating enzyme
-
-
-
-
putrescine acetylase
-
-
-
-
putrescine acetyltransferase
-
-
-
-
putrescine N-acetyltransferase
-
-
-
-
spermidine acetyltransferase
-
-
-
-
spermidine N1-acetyltransferase
-
-
-
-
spermidine/spermine N1-acetyltransferase
SSAT
additional information
-
SSAT is a member of the GCN5-related N-acetyltransferase, GNAT, family
spermidine/spermine N1-acetyltransferase
-
-
-
-
spermidine/spermine N1-acetyltransferase
-
-
SSAT
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:alkane-alpha,omega-diamine N-acetyltransferase
Acts on propane-1,3-diamine, pentane-1,5-diamine, putrescine, spermidine (forming N1- and N8-acetylspermidine), spermine, N1-acetylspermidine and N8-acetylspermidine.
CAS REGISTRY NUMBER
COMMENTARY
54596-36-0
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + 1,3-diaminopropane
CoA + N1-acetyl-1,3-diaminopropane
-
-
-
?
acetyl-CoA + diethylenetriamine
CoA + N1-acetyl-diethylenetriamine
-
-
-
?
acetyl-CoA + eIF5A
CoA + acytyl-eIF5A
-
selective acetylation of the hypusine and/or deoxyhypusine residue of translation initiation factor eIF5A, resulting in loss of eIF5A activity. Hypusine or deoxyhypusine, as the free amino acid, do not act as a substrate for isoform SSAT1
-
?
acetyl-CoA + N1-acetylspermine
CoA + N1,N12-diacetylspermine
-
-
-
?
acetyl-CoA + triethylenetetramine
?
SSAT2 is the main acetylator of TETA compared to SSAT1
-
-
?
chloroacetyl-CoA + spermine
N1-spermine-acetyl-CoA + ?
N1-chloroacetylation of spermine performed by hSSAT protein, pH 7.5 and 2 microM recombinant human SSAT protein at room temperature for one hour, identity of the product confirmed by mass spectrometry
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
-
?
acetyl-CoA + (S)-2-[(3-aminopropyl)amino]ethylphosphoric acid
CoA + N-acetyl-(S)-2-[(3-aminopropyl)amino]ethylphosphoric acid
-
WR-2721, about 10% of the rate with spermidine
-
-
?
acetyl-CoA + (S)-2-[(3-aminopropyl)amino]propylphosphoric acid
CoA + N-acetyl-(S)-2-[(3-aminopropyl)amino]propylphosphoric acid
-
WR-44923, about 10% of the rate with spermidine
-
-
?
acetyl-CoA + 15-deoxyspergualin
?
-
antitumor and immunosuppressive agent 15-deoxyspergualin, about 18% of the rate with spermidine
-
-
?
acetyl-CoA + 2-[(aminopropyl)amino]ethanethiol
CoA + N-acetyl-2-[(aminopropyl)amino]ethanethiol
-
radioprotective drug WR-1065, lower affinity than for spermidine, about 10% of the rate with spermidine
-
-
?
acetyl-CoA + 6,6-difluorospermidine
CoA + N1-acetyl-6,6-difluorospermidine
-
16.6% of the rate with spermidine
-
-
?
acetyl-CoA + 7,7-difluorospermidine
CoA + N1-acetyl-7,7-difluorospermidine
-
19.7% of the rate with spermidine
-
-
?
acetyl-CoA + N-(n-butyl)-1,3-diaminopropane
CoA + N1-acetyl-N3-(n-butyl)-1,3-diaminopropane
-
weak substrate, lower affinity than for spermidine, 1.3% of the rate with spermidine
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
?
3 acetyl-CoA + spermidine
3 CoA + N1,N4,N8-triacetylspermidine
-
-
-
?
3 acetyl-CoA + spermidine
3 CoA + N1,N4,N8-triacetylspermidine
-
-
-
?
acetyl-CoA + 1,12-diamino-3,6,9-triazadodecane
?
an extremely poor substrate of human recombinant SSAT2, that is metabolized by SSAT1 in Hep-G2 cells and in wild-type primary hepatocytes
-
-
?
acetyl-CoA + 1,12-diamino-3,6,9-triazadodecane
?
SSAT1 is the main acetylator of 1,12-diamino-3,6,9-triazadodecane compared to SSAT2
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
mimics of transition state of SSAT1 reaction analyzed
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) crucial for regulation of the cellular polyamine levels in eukaryotic cells
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
mimics of transition state of SSAT1 reaction analyzed
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) crucial for regulation of the cellular polyamine levels in eukaryotic cells, chemical and kinetic mechanism for acetyl transfer activity by recombinant human SSAT protein proposed
-
-
?
acetyl-CoA + N1-acetylspermine
CoA + N1,N12-diacetylspermine
-
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
product is exclusively N1-acetylspermidine
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
product is exclusively N1-acetylspermidine
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
product is exclusively N1-acetylspermidine
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
N1-acetylspermidine is the major product
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
spermidine acetylation might be a strategy for inhibiting growth in response to environmental stresses
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
catabolism of spermidine and spermine
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
catabolism of spermidine and spermine
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
-
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
about 40% of the rate with spermidine
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
catabolism of spermidine and spermine
-
-
?
additional information
?
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
substrate specificity of isozyme SSAT-1 in descending order: norspermidine equal spermidine, spermine, N1-acetylspermine, putrescine
-
-
?
additional information
?
-
substrate specificity of isozyme SSAT-1 in descending order: norspermidine equal spermidine, spermine, N1-acetylspermine, putrescine
-
-
?
additional information
?
-
-
substrate specificity of isozyme SSAT-1 in descending order: norspermidine equal spermidine, spermine, N1-acetylspermine, putrescine
-
-
?
additional information
?
-
substrate specificity of isozyme SSAT-2 in descending order: norspermidine, spermidine equal spermine, N1-acetylspermine equal putrescine
-
-
?
additional information
?
-
substrate specificity of isozyme SSAT-2 in descending order: norspermidine, spermidine equal spermine, N1-acetylspermine equal putrescine
-
-
?
additional information
?
-
-
substrate specificity of isozyme SSAT-2 in descending order: norspermidine, spermidine equal spermine, N1-acetylspermine equal putrescine
-
-
?
additional information
?
-
roles of SSAT proteins in oxygen homeostasis, SSAT1 binding to hypoxia-inducible factor-1 (HIF-1alpha) promotes its ubiquitination/degradation, in contrast to SSAT2, SSAT1 acts by stabilizing the interaction of HIF-1alpha with RACK1
-
-
?
additional information
?
-
the enzyme transforms polyamines into putrescine
-
-
?
additional information
?
-
-
the enzyme transforms polyamines into putrescine
-
-
?
additional information
?
-
human SSAT1 binds to the PAS-B (Per-ARNT-Sim) domain of HIF-1alpha, a key regulator of oxygen homeostasis in all metazoans, facilitating its degradation
-
-
?
additional information
?
-
-
human SSAT1 binds to the PAS-B (Per-ARNT-Sim) domain of HIF-1alpha, a key regulator of oxygen homeostasis in all metazoans, facilitating its degradation
-
-
?
additional information
?
-
-
Lys-141 is the first residue in a KRR motif that makes up part of the active site
-
-
?
additional information
?
-
-
enzyme requires a substrate with the structure H2N(CH2)3NHR and acetylates the primary amino group
-
-
?
additional information
?
-
-
acetylation is a physiological response to convert excess polyamines to a physiologically inert form which is readily excreted
-
-
?
additional information
?
-
-
enzyme plays an efficient role in maintaining polyamine pool homeostasis during challenges with exogenous polyamines
-
-
?
additional information
?
-
-
rate-limiting enzyme in the degradation and interconversion of polyamines
-
-
?
additional information
?
-
-
SSAT prevents overaccumulation of higher polyamines from becoming toxic to cell and maintains a balanced ratio of polyamines according to cellular needs
-
-
?
additional information
?
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
substrate specificity of isozyme SSAT-2 in descending order: norspermidine, spermidine equal spermine, N1-acetylspermine equal putrescine
-
-
?
additional information
?
-
substrate specificity of isozyme SSAT-2 in descending order: norspermidine, spermidine equal spermine, N1-acetylspermine equal putrescine
-
-
?
additional information
?
-
-
substrate specificity of isozyme SSAT-2 in descending order: norspermidine, spermidine equal spermine, N1-acetylspermine equal putrescine
-
-
?
additional information
?
-
-
the enzyme functions as a coactivator for NF-kappaB and cooperates with CREB-binding protein and the p300/CBP-associated factor to enhance NF-kappaB-dependent transcription
-
-
?
additional information
?
-
-
polyamines regulate SSAT mRNA translational efficiency by inhibiting a repressor protein from binding to regions of the coding sequence of the SSAT transcript
-
-
?
additional information
?
-
-
N1,N11-diethylnorspermine induces apoptosis involving increased SSAT activity and the mitochondria of the cell
-
-
?
additional information
?
-
-
simultaneous drug combination or quinoxaline pre-treatment synergistically increases SSAT expression, depletes polyamines, increases reactive oxygen species production, and produces synergistic tumor cell killing in both cell lines, overview. Cisplatin-resistant human ovarian cell line, A2780/CP cells, cannot be induced by spermidine analogues, in contrast to the sensitive counterpart A2780
-
-
?
additional information
?
-
-
SSAT binds to the HIF-1alpha subunit and promotes its ubiquitination and degradation. SSAT transcriptional regulation, regulation of SSAT protein levels by polyamines or analogues, SSAT protein turnover, overview. Upregulation of the Sat1 gene transcription is critical for the cell-specific polyamine or analog-mediated increase in SSAT content
-
-
?
additional information
?
-
-
SSAT expression causes arrest of cell cycle and cell growth in the S-phase in transfected cells through a mechanism involving the suppression of cyclin A and E2F1-expression, overview
-
-
?
additional information
?
-
-
SSAT induction increased metabolic flux by about 5fold, overview. The metabolic flux can be interrupted by inhibition of polyamine biosynthesis but not by inhibition of polyamine oxidation
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + 1,12-diamino-3,6,9-triazadodecane
?
an extremely poor substrate of human recombinant SSAT2, that is metabolized by SSAT1 in Hep-G2 cells and in wild-type primary hepatocytes
-
-
?
acetyl-CoA + eIF5A
CoA + acytyl-eIF5A
-
selective acetylation of the hypusine and/or deoxyhypusine residue of translation initiation factor eIF5A, resulting in loss of eIF5A activity. Hypusine or deoxyhypusine, as the free amino acid, do not act as a substrate for isoform SSAT1
-
?
acetyl-CoA + triethylenetetramine
?
SSAT2 is the main acetylator of TETA compared to SSAT1
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
?
3 acetyl-CoA + spermidine
3 CoA + N1,N4,N8-triacetylspermidine
-
-
-
?
3 acetyl-CoA + spermidine
3 CoA + N1,N4,N8-triacetylspermidine
-
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) crucial for regulation of the cellular polyamine levels in eukaryotic cells
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
spermidine acetylation might be a strategy for inhibiting growth in response to environmental stresses
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
catabolism of spermidine and spermine
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
catabolism of spermidine and spermine
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
-
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
catabolism of spermidine and spermine
-
-
?
additional information
?
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
the enzyme transforms polyamines into putrescine
-
-
?
additional information
?
-
-
the enzyme transforms polyamines into putrescine
-
-
?
additional information
?
-
-
acetylation is a physiological response to convert excess polyamines to a physiologically inert form which is readily excreted
-
-
?
additional information
?
-
-
enzyme plays an efficient role in maintaining polyamine pool homeostasis during challenges with exogenous polyamines
-
-
?
additional information
?
-
-
rate-limiting enzyme in the degradation and interconversion of polyamines
-
-
?
additional information
?
-
-
SSAT prevents overaccumulation of higher polyamines from becoming toxic to cell and maintains a balanced ratio of polyamines according to cellular needs
-
-
?
additional information
?
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
?
additional information
?
-
-
the enzyme functions as a coactivator for NF-kappaB and cooperates with CREB-binding protein and the p300/CBP-associated factor to enhance NF-kappaB-dependent transcription
-
-
?
additional information
?
-
-
N1,N11-diethylnorspermine induces apoptosis involving increased SSAT activity and the mitochondria of the cell
-
-
?
additional information
?
-
-
simultaneous drug combination or quinoxaline pre-treatment synergistically increases SSAT expression, depletes polyamines, increases reactive oxygen species production, and produces synergistic tumor cell killing in both cell lines, overview. Cisplatin-resistant human ovarian cell line, A2780/CP cells, cannot be induced by spermidine analogues, in contrast to the sensitive counterpart A2780
-
-
?
additional information
?
-
-
SSAT binds to the HIF-1alpha subunit and promotes its ubiquitination and degradation. SSAT transcriptional regulation, regulation of SSAT protein levels by polyamines or analogues, SSAT protein turnover, overview. Upregulation of the Sat1 gene transcription is critical for the cell-specific polyamine or analog-mediated increase in SSAT content
-
-
?
additional information
?
-
-
SSAT expression causes arrest of cell cycle and cell growth in the S-phase in transfected cells through a mechanism involving the suppression of cyclin A and E2F1-expression, overview
-
-
?
additional information
?
-
-
SSAT induction increased metabolic flux by about 5fold, overview. The metabolic flux can be interrupted by inhibition of polyamine biosynthesis but not by inhibition of polyamine oxidation
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N1-spermine-acetyl-CoA
bisubstrate analogue, bisubstrate inhibition patterns determined, linear, competitive inhibition against sperimidine and acetyl-CoA determined
additional information
synthetic peptide IVEMSTSKTGK50HGHAK modeled on the sequence of amino acids surrounding the hypusine residue K50, 50% inhibition of eIF5A acetylation at 0.05 mM
-
additional information
conjugates of symmetrical polyamines spermine , 1,12-diamino-4,9-diazadodecane and of nor-spermidine, 1,7-diamino-4-azaheptane, with coenzyme A, mimicking intermediate the coenzyme-substrate complex, are synthesized to inhibit the enzyme, overview
-
additional information
-
folate cycle inhibitors, with quinoxaline moieties 3-methyl-7-trifluoromethyl-2(R)-[3,4,5-trimethoxyanilino]-quinoxaline or 3-piperazinilmethyl-2[4(oxymethyl)-phenoxy]quinoxaline, affect the enzyme, simultaneous drug combination or quinoxaline pre-treatment synergistically increases SSAT expression, depletes polyamines, increases reactive oxygen species production, and produces synergistic tumor cell killing in both cell lines, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N1,N11-bis-(ethyl)-norspermine
-
induces mRNA and activity of SSAT protein, translation proceeded by competition of a predicted RNA-binding protein
N1,N11-diethylnorspermine
-
polyamine analogue with clinical relevance as an experimental anticancer agent. Treatment of human C-28/I2 chondrocytes rapidly induces spermidine/spermine N1-acetyltransferase and spermine oxidase activities, and down-regulates ornithine decarboxylase. The treatment does not provoke cell death and caspase activation when given alone for 24 h, but causes a caspase-3 and -9 dependent apoptosis in chondrocytes further exposed to cycloheximide. The simultaneous addition of N1,N11-diethylnorspermine and cycloheximide rapidly increases caspase activity in C-28/I2 cells in the absence of spermidine/spermineN1-acetyltransferase and spermine oxidase induction or significant reduction of polyamine levels. Caspase activation induced by N1,N11-diethylnorspermine plus cycloheximide is not prevented by a N1-acetylpolyamine oxidase inhibitor
additional information
-
indomethacin and excess polyamines induce SSAT activity
-
additional information
-
N1,N12-bis(ethyl)spermine is a potent inducer of enzyme in human tumor cells
-
additional information
-
enzyme is highly inducible by polyamine analogues such as N1,N12-bis(ethyl)spermine and N1,N11-bis(ethyl)norspermine, they prevent enzyme degradation via the Ub/proteasome pathway, mechanism
-
additional information
-
enzyme is induced by methylglyoxal bis(guanylhydrazone), potentiated by tetronasin or felodipine, tetronasin is also an active inducer, induction is related to the concentration of intracellular free calcium
-
additional information
-
enzyme is induced by isopropyl beta-D-thiogalactopyranoside
-
additional information
-
enzyme is induced by isopropyl beta-D-thiogalactopyranoside
-
additional information
-
N1,N11-diethylnorspermine induces SSAT mRNA and activity
-
additional information
-
certain stresses induce enzyme by a spermidine-dependent post-transcriptional mechanism, e.g. heat shock, diethyldithiocarbamate and high levels of endogenous spermidine, alpha-difluoromethylornithine inhibits stress induction
-
additional information
-
amino acid deprivation upregulates enzyme expression level of 2 different mRNA forms
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.106
1,12-diamino-3,6,9-triazadodecane
pH and temperature not specified in the publication
0.107
1,3-diaminopropane
measured at fixed saturating concentrations of acetyl-CoA
0.0038
acetyl-CoA
measured at fixed saturating concentration of spermidine
0.194
diethylenetriamine
measured at fixed saturating concentrations of acetyl-CoA
0.196
ethylenediamine
measured at fixed saturating concentrations of acetyl-CoA
0.022
spermidine
measured at fixed saturating concentrations of acetyl-CoA
0.0057
spermine
measured at fixed saturating concentrations of acetyl-CoA
0.083
triethylenetetramine
pH and temperature not specified in the publication
additional information
additional information
no detectable activity for putrescine and cadaverine
-
additional information
additional information
-
no detectable activity for putrescine and cadaverine
-
additional information
additional information
-
Km value for spermine is lower than that for N1-acetylspermine
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.006
N1-spermine-acetyl-CoA
bisubstrate analogue, linear, competitive inhibition, structure of hSSAT with bound N1-spermine-acetyl-CoA determined
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.00007
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate putrescine
0.00008
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate N1-acetylspermine
0.00009
recombinant HEK-293 cells expressing isozyme SSAT-1, substrate putrescine
0.0002
recombinant HEK-293 cells expressing isozyme SSAT-1, substrate N1-acetylspermine
0.00023
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate spermine
0.00025
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate spermidine
0.0004
recombinant HEK-293 cells expressing isozyme SSAT-1, substrate spermine
0.00068
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate norspermidine
0.001
recombinant HEK-293 cells expressing isozyme SSAT-1, substrate spermidine
0.0011
recombinant HEK-293 cells expressing isozyme SSAT-1, substrate norspermidine
0.00007
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate putrescine
0.00008
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate N1-acetylspermine
0.00023
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate spermine
0.00025
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate spermidine
0.00068
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate norspermidine
additional information
additional information
kinetic and mechanistic characterization, determination of bisubstrate inhibition patterns, three-dimensional structure of the recombinant human SSAT protein with bound bisubstrate inhibitor, acid/base assisted reaction catalyzed by SSAT involves a ternary complex, proposed on the base of kinetic properties, pH dependence and structure analysis
additional information
-
kinetic and mechanistic characterization, determination of bisubstrate inhibition patterns, three-dimensional structure of the recombinant human SSAT protein with bound bisubstrate inhibitor, acid/base assisted reaction catalyzed by SSAT involves a ternary complex, proposed on the base of kinetic properties, pH dependence and structure analysis
additional information
SSAT1 inhibits hypoxia-inducible factor-1 (HIF-1alpha) through protein/protein interaction, effect of SSAT1 loss of function on HIF-1alpha protein levels and HIF-1 transcriptional activity, mutation of Arg101 impairs SSAT1-mediated HIF-1alpha degradation, SSAT1 promotes the ubiquitination of HIF-1alpha, involvement of SSAT1 and SSAT2 in alternative pathways for ubiquitination and degradation of HIF-1alpha, complementary roles in promoting O2-independent and O2-dependent degradation of HIF-1alpha
additional information
structure of polyamine fragment of the conjugate important for enzyme activity, existence of adenosine groups crucial for effective inhibition, since conjugates of D-N-pantothenylamidoethyl mercaptane family reveals low inhibitory activities, most exact mimic of the intermediate of N1-acetyltransferase reaction less active than analogue of the intermediate of N8-acetyltransferase reaction, significant contribution of the polyamine fragment into inhibition proven by lower activity
additional information
-
regulation of SSAT expression, de novo RNA and protein synthesis analyzed, two regions of the SSAT protein coding sequence involved in translational repression of SSAT in the absence of elevated polyamine levels, RNA-binding protein possibly interacting with stem-loop structures to block translation can be displaced by the polyamine analogue N1,N11-bis-(ethyl)-norspermine (DENSPM), allowing translation to proceed, 5' and 3' polyamine-responsive regions interact with each other in vivo, changes in either region result in translation in the absence of the polyamine analogue N1,N11-bis-(ethyl)-norspermine
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.7 - 9.1
activity monitored every 0.3 pH units, bell shaped pH activity profile, depending on ionization state of two groups with apparent pKa values of 7.27 and 8.87
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
synovial fibroblasts from patients with rheumatoid arthritis or osteoarthritis
-
enzyme expression in reduced in brain Brodmann areas,i.e. in BA4, BA8/9, and BA11, of suicide completers
-
activity of SSAT is increased 28fold in tetracycline-induced cells. Increase in SSAT levels in HEK-293 cells leads to depletion of polyamines and elevation in the enzymatic activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, suggestive of a compensatory reaction to increased polyamine catabolism. Increased expression of SSAT also leads to DNA damage and G2 arrest
-
TNFalpha can lead to the induction of NFkappaB signaling with a concomitant increase in spermidine/spermine N1-acetyltransferase expression
-
A549 and H157. TNFalpha can lead to the induction of NFkappaB signaling with a concomitant increase in spermidine/spermine N1-acetyltransferase expression
-
TNFalpha can lead to the induction of NFkappaB signaling with a concomitant increase in spermidine/spermine N1-acetyltransferase expression
-
in breast tumors, SSAT is increased contributing to an increase in acetylated polyamines
-
induction by aspirin and different non-steroidal anti-inflammatory drugs
-
the enzyme is inducible in response to 5-fluorouracil or oxaliplatin in parental and drugresistant HCT116 cell lines
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
recombinant enzyme, expressed in Escherichia coli DH5alpha, is present at a level of about 2% of the soluble protein
-
-
mitochondrial uptake may be regulated by the phosphorylation state of SSAT
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
phylogenetic analysis of ssat-like genes dividing the genes into 3 clusters, comparison of zebrafish and human gene sequences and regulation, overview
malfunction
metabolism
spermidine/spermine N1-acetyltransferase 1 is a key enzyme in the polyamine interconversion pathway, which maintains polyamine homeostasis
physiological function
malfunction
metabolism
physiological function
malfunction
enzyme inhibition also inhibits ongoing joint destruction. Enzyme inhibition or gene silencing by transfection of siRNA targeting SSAT-1 increases 5-methylcytosine levels/PMF-1 promoter methylation within 21 days
malfunction
key polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase1 overexpression in HEK293T cells via adenoviral vector leads to a rapid depletion of spermidine and spermine, arrest in cell growth and a decline in cell viability. AdSAT1-transduced cells reveal morphological changes commonly associated with apoptosis, including cell shrinkage, nuclear fragmentation, mitochondrial alteration, vacuolization and membrane blebbing. As polyamine analogues, alpha-methylspermidine and N1,N12-dimethylspermine that are not substrates for SAT1 partially restore growth and prevent apoptosis of AdSAT1-transduced cells. Inhibition of polyamine oxidases does not restore the growth of AdSAT1-transduced cells or block apoptosis. AdSAT1-transduction causes apoptosis by an intrinsic mitochondrial pathway, release of cytochrome c from mitochondria to cytoplasm concomitant with a decrease in the mitochondrial fraction in AdSAT1-transduced cells
malfunction
SSAT1 knockdown leads to a dramatic reduction of N1-acetyylspermidine and N1-acetylspermine pools. Metabolism of 1,12-diamino-3,6,9-triazadodecane to N1-acetyl-1,12-diamino-3,6,9-triazadodecane is reduced with SSAT1 but not with SSAT2 shRNA. No metabolism of 1,12-diamino-3,6,9-triazadodecane detectable in SSAT1-KO cells. In wild-type cells, SSAT2 knockdown does not reduce the metabolism of 1,12-diamino-3,6,9-triazadodecane to N1-AcSpmTrien. In fact it leads to the induction of SSAT1 activity and increased metabolism of 1,12-diamino-3,6,9-triazadodecane to N1-acetyl-1,12-diamino-3,6,9-triazadodecane
malfunction
the enzyme is underexpressed in brains from suicide victims compared to controls
physiological function
polyamines (agmatine, putrescine, spermine and spermidine) are ubiquitous molecules involved in cell growth and differentiation. They modulate neurotransmission and are responsible for the polyamine mediated stress response, a cascade of molecular events transiently activated by acute stress stimuli. Chronic stress can lead to a hyperactivation of the polyamine system, ultimately leading to cell growth inhibition and cell death. Spermidine/spermine N1-acetyltranserare 1 is the key regulator of cellular polyamine content and is involved in the catabolism of spermidine and spermine, a key step in the maintenance of polyamine homeostasis
physiological function
the enzyme maintains polyamine homeostasis, mammalian Ssat1 is also involved in many physiological and pathological events such as hypoxia, cell migration, and carcinogenesis
malfunction
-
altered expression of SAT1 in the polyamine stress response, across multiple brain regions between control individuals and depressed individuals who have died by suicide, overview
malfunction
-
SSAT overexpression may be linked to the rare X-linked disease keratosis follicularis spinulosa decalvans
physiological function
-
SAT1 is the rate-limiting enzyme involved in catabolism of the polyamines spermidine and spermine
physiological function
-
SSAT regulates cellular polyamine content and links polyamine metabolism to lipid and carbohydrate metabolism by means of alterations in the content of acetyl-CoA and ATP. Since polyamines play critical roles in normal and neoplastic growth and in ion channel regulation, SSAT is a key enzyme in these processes. A high level of SSAT stimulates flux through the polyamine biosynthetic pathway
physiological function
-
depletion of polyamines by the enzyme significantly inhibits cell proliferation, migration and invasion through AKT/GSK3beta/beta-catenin signaling pathway in hepatocellular carcinoma and colorectal cancer cells. The enzyme inhibits cell colony formation and proliferation rate in hepatocellular and colorectal carcinoma cells
physiological function
-
the enzyme regulates the genes MELK and EZH2 by direct interaction with chromatin
physiological function
-
the enzyme restricts chikungunya virus and Zika virus replication. The enzyme depletes spermidine and spermine to restrict RNA virus replication
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SAT1_HUMAN
171
0
20024
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21000
-
x * 21000 + x * 23000, two bands, enzyme is probably a tetramer, recombinant enzyme, SDS-PAGE
23000
-
x * 21000 + x * 23000, two bands, enzyme is probably a tetramer, recombinant enzyme, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
two dimer conformations are observed: a symmetric form with two open surface channels capable of binding substrate or cofactor, and an asymmetric form in which only one of the surface channels appears capable of binding and acetylating polyamines
homodimer
tetramer
-
x * 21000 + x * 23000, two bands, enzyme is probably a tetramer, recombinant enzyme, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
no modification
-
no posttranslational modification specific to eukaryotes is needed for enzyme activity
phosphoprotein
additional information
-
selfacetylation of Lys26 in the presence of acetyl-cCoA and in absence of substrate
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
three-dimensional crystal structure of SSAT with bound bisubstrate inhibitor, solved at 2.3 A resolution, hanging drop method, data and refinement statistics
precipitation with polyethylene glycol, high resolution structures of wild-type and mutant SSAT, as the free dimer and in binary and ternary complexes with CoA, acetyl-CoA, spermine, and the inhibitor N1,N11-bis-(ethyl)-norspermine
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
R101K
site-directed mutagenesis of SSAT1 protein, ability to promote hypoxia-inducible factor-1 (HIF-1alpha) degradation reduced
E152Q
-
mutation disrupts binding of stabilizing N1,N12-bis(ethyl)spermine to enzyme
E171Q
-
mutation results in a marked stabilization of enzyme, due to the lack of formation of high-molecular-mass complexes with ubiquitin
K111R
-
mutant with the same activity as wild-type enzyme, but reduced half-life
K141R
-
mutant with 35% of activity of wild-type enzyme, increased Km for spermidine and reduced half-life
K87R
-
mutant with 70% of activity of wild-type enzyme, but significantly longer half-life, suggesting that Lys-87 may be the preferred site for ubiquination
additional information
additional information
knockdown of enzyme SSAT1 in Hep-G2 cells and in primary hepatocytes
additional information
-
knockdown of enzyme SSAT1 in Hep-G2 cells and in primary hepatocytes
additional information
small interfering RNAs (siRNAs) against SSAT-1 are transfected weekly in rheumatoid arthritis synovial fibroblasts
additional information
-
small interfering RNAs (siRNAs) against SSAT-1 are transfected weekly in rheumatoid arthritis synovial fibroblasts
additional information
-
18 promoter polymorphisms of SAT1 are identified in French-Canadian population, haplotypes and genotyping, overview
additional information
-
transgenic overexpression of SSAT protects from kainate and epilepsy-like seizure activity induction by pentylenetetrazol
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
native protein conformation is unstable, polyamine analogues such as N1,N12-bis(ethyl)spermine greatly stabilize, conformational changes caused by their binding prevent the efficient polyubiquination of enzyme and therefore its degradation
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant N-terminally GST- or His6-tagged enzyme from Escherichia coli strain BL21 by affinity chromatography
62fold purification of recombinant enzyme, expressed in Escherichia coli DH5alpha
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination of isozyme SSAT-2, localization of isozyme SSAT-2 on chromosome 17p13.1, expression of isozyme SSAT-2 in HEK-293 cells
expressed in Escherichia coli BL21-Gold(DE3)pLysS cells, transformed with pGEX expression vectors
expressed in Escherichia coli, strains Nova Blue and BL21(DE3), plasmid pET-28a
gene sat1, quantitative one-step real-time PCR enzyme expression analysis
gene ssat1, sequence comparison, expression profile, and phylogenetic analysis of ssat-like genes, recombinant expression of N-terminally GST- or His6-tagged enzyme in Escherichia coli strain BL21, recombinant expression in HEK-293T cells
transduction of HEK-293T cells with an adenovirus encoding the enzyme and enzyme overexpression
cloning and conditional expression of cDNA encoding enzyme in Escherichia coli CAG2242 results in a decrease of endogenous spermidine contents and growth rates
-
cloning and expression of cDNA encoding enzyme in Escherichia coli DH5alpha leads to a significant reduction in the cell growth rate
-
complete SSAT cDNA is cloned, tetracyclin-regulated cDNA is expressed in MCF-7 human breast carcinoma cells, conditional overexpression lowers polyamine pools, inhibits cell growth and enhances growth sensitivity to certain analogs
-
DNA and amino acid sequence determination of isozyme SSAT-2, localization of isozyme SSAT-2 on chromosome 17p13.1, expression of isozyme SSAT-2 in HEK-293 cells
enzyme expression, with or without fused luciferase gene, in HeLa cells possessing a stress-activated protein/extracellular signal-regulated protein kinase, amino acid deprivation upregulates enzyme expression level of 2 different mRNA forms, the effects of different amino acids, especially leucine, arginine, and methionine, are differently high and long-lasting, expression analysis under different conditions, overview
-
expressed in Escherichia coli, FLAG-tagged SSAT protein and SSAT protein fused to Renilla luciferase
-
expression of SSAT in HT-29 cells and LoVo cells, two colorectal cancer cell lines, using an adenoviral vector, recombinant enzyme expression causes arrest of cell cycle and cell growth in the S-phase
-
expression of SSAT in MGC803 and SGC7901 cells, two gastric cancer cell lines, using an adenoviral vector, recombinant enzyme expression inhibits cell growth in vitro and in vivo, Ad-SSAT arrests gastric cancer cells in S phase, mediated through downregulation of the cyclin A-E2F signaling pathway, polyamine contents in the cells, overview
-
gene Sat1, located on the X chromosome at Xp22.1, DNA and amino acid sequence analysis, genetic structure, overview
-
plasmid pSAT9.3, containing SSAT cDNA cloned into Bluescript vector, is used to express the protein from the T7 promoter using rabbit reticulocyte TNT coupled expression system
-
SAT1, microarray expression analysis in brains of control individuals and depressed individuals who have died by suicide, overview
-
SSAT overexpression in prostate cancer cells leads to a massive increase in intracellular and extracellular acetylated spermidine and to a 6-20fold increase in biosynthetic enzyme activities, overview. In the presence of 4-fluoro-ornithine, SSAT overexpression leads to the sequential appearance of fluorinated putrescine, spermidine, acetylated spermidine, and spermine
-
transfection of the SSAT repressed C13 cells with two expression vectors driving human SSAT overexpression by diverse promoters. SSAT overexpression inhibits cell growth and enhances growth sensitivity to N1,N12-bis(ethyl)spermine in C13 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
lithium induces enzyme expression in low and high risk groups for suicide commitment as well as in controls, but it has no effect in suicide completers. Differences in lithium-induced increase in SAT1 mRNA levels, overview
high levels of enzyme expression are measured in tumor human cell lines, and in breast, prostate and lung tumor tissue. Increases in enzyme protein contents and gene expression in primary tumors is linked to a concomitant higher level of N1-acetylamantadine in urine of cancer patients upon ingestion of amantadine
-
induction of SSAT gene expression by combined quinoxalines and spermidine analogue treatment, overview. The cDDP-resistant human ovarian cell line, A2780/CP, shows defective expression and inducibility of SSAT by Spm analogues, when compared to the sensitive counterpart A2780
-
protein expression of the enzyme is significantly up-regulated in hepatocellular carcinoma and colorectal cancer cells
-
the enzyme is upregulated by type I interferon beta stimulation (10000 units/ml for 16 h) or treatment with N1,N11-diethylnorspermine (0.01 mM for 16 h)
-
treatment of some human cancer cells, such as NCI H157 human lung carcinoma cells, with polyamine analogues N1,N12-bis(ethyl)spermine or N1,N11-bis-(ethyl)norspermine leads to a very high induction of SSAT. SSAT activity is induced via a variety of other stimuli, including toxins, hormones, cytokines, nonsteroidal anti-inflammatory agents, natural products, and stress pathways, and by ischemia-reperfusion injury. Effects of increased SSAT activity include death of pancreatic cells, blockage of regenerative tissue growth, behavioral changes, keratosis follicularis spinulosa decalvans, and hair loss. Polyamine analogs such as BE-3-3-3 or BE-3-4-3 cause a huge increase in Sat1 gene expression in certain tumor cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
-
SSAT may also be a useful target in diseases other than cancer
medicine
pharmacology
-
compounds capable of potently inducing SSAT and having favorable pharmacological properties in animals are potential anticancer agents
medicine
-
induction of enzyme may be critical for the inhibition of tumor cell growth
medicine
-
development of SSAT induction strategies to circumvent the ability of tumor cells to escape the antitumor activity of polyamine inhibitors such as alpha-difluoromethylornithine by salvaging exogenous polyamines
medicine
-
the ability of polyamine analogues to induce N1SSAT activity correlates with the ability to inhibit growth and viability of human tumor-derived cells
medicine
-
activation of the enzyme by aspirin and different non-steroidal anti-inflammatory drugs may be a common property of non-steroidal anti-inflammatory drugs that plays an important role in their chemopreventive actions in colorectal cancer
medicine
-
in kidneys subjected to ischemia-reperfusion injury, one mechanism through which increased expression of SSAT may cause cellular injury and organ damage is through induction of DNA damage and the disruption of cell cycle
medicine
-
the enzyme may be an important target for therapeutic intervention in colorectal cancer
medicine
-
treatment of human C-28/I2 chondrocytes with polyamine analogue N1,N11-diethylnorspermine rapidly induces spermidine/spermine N1-acetyltransferase and spermine oxidase activities, and down-regulates ornithine decarboxylase. The treatment does not provoke cell death and caspase activation when given alone for 24 h, but causes a caspase-3 and -9 dependent apoptosis in chondrocytes further exposed to cycloheximide. The simultaneous addition of N1,N11-diethylnorspermine and cycloheximide rapidly increases caspase activity in C-28/I2 cells in the absence of spermidine/spermineN1-acetyltransferase and spermine oxidase induction or significant reduction of polyamine levels. Caspase activation induced by N1,N11-diethylnorspermine plus cycloheximide is not prevented by a N1-acetylpolyamine oxidase inhibitor
medicine
-
amantadine can be used to determine enzyme cellular activity by measuring excretion of N1-acetylamantadine which may indicate the presence of cancer
medicine
-
the enzyme is a veritable therapeutic target in glioblastoma that controls tumor cell stemness and aggressiveness. The enzyme promotes resistance to radiotherapy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Quick, D.M.; Wallace, H.M.
Induction of spermidine/spermine N1-acetyltransferase in human breast carcinoma cells. A possible role for calcium
Biochem. Pharmacol.
46
969-974
1993
Homo sapiens
Parry, L.; Lopez-Ballester, J.; Wiest, L.; Pegg, A.E.
Effect of expression of human spermidine/spermine N1-acetyltransferase in Escherichia coli
Biochemistry
34
2701-2709
1995
Homo sapiens
Ignatenko, N.A.; Fish, J.L.; Shassetz, L.R.; Woolridge, D.P.; Gerner, E.W.
Expression of the human spermidine/spermine N1-acetyltransferase in spermidine acetylation-deficient Escherichia coli
Biochem. J.
319
435-440
1996
Homo sapiens
-
Gerner, E.W.; Kurtts, T.A.; Fuller, D.J.M.; Casero, R.A., Jr.
Stress induction of the spermidine/spermine N1-acetyltransferase by a post-transcriptional mechanism in mammalian cells
Biochem. J.
294
491-495
1993
Cricetulus griseus, Homo sapiens
-
Vujcic, S.; Halmekyto, M.; Diegelman, P.; Gan, G.; Kramer, D.L.; Janne, J.; Porter, C.W.
Effects of conditional overexpression of spermidine/spermine N1-acetyltransferase on polyamine pool dynamics, cell growth, and sensitivity to polyamine analogs
J. Biol. Chem.
275
38319-38328
2000
Homo sapiens, Mus musculus
Coleman, C.S.; Pegg, A.E.
Polyamine analogues inhibit the ubiquitination of spermidine/spermine N1-acetyltransferase and prevent its targeting to the proteasome for degradation
Biochem. J.
358
137-145
2001
Homo sapiens
Turchanowa, L.; Dauletbaev, N.; Milovic, V.; Stein, J.
Nonsteroidal anti-inflammatory drugs stimulate spermidine/spermine acetyltransferase and deplete polyamine content in colon cancer cells
Eur. J. Clin. Invest.
31
887-893
2001
Homo sapiens
Chen, Y.; Vujcic, S.; Liang, P.; Diegelman, P.; Kramer, D.L.; Porter, C.W.
Genomic identification and biochemical characterization of a second spermidine/spermine N1-acetyltransferase
Biochem. J.
373
661-667
2003
Homo sapiens (P21673), Homo sapiens (Q96F10), Homo sapiens
Aubel, C.; Chabanon, H.; Carraro, V.; Wallace, H.M.; Brachet, P.
Expression of spermidine/spermine N1-acetyltransferase in HeLa cells is regulated by amino acid sufficiency
Int. J. Biochem. Cell Biol.
35
1388-1398
2003
Homo sapiens
Zahedi, K.; Bissler, J.J.; Wang, Z.; Josyula, A.; Lu, L.; Diegelman, P.; Kisiel, N.; Porter, C.W.; Soleimani, M.
Spermidine/spermine N1-acetyltransferase overexpression in kidney epithelial cells disrupts polyamine homeostasis, leads to DNA damage, and causes G2 arrest
Am. J. Physiol. Cell Physiol.
292
C1204-C1215
2007
Homo sapiens
Babbar, N.; Gerner, E.W.; Casero, R.A.
Induction of spermidine/spermine N1-acetyltransferase (SSAT) by aspirin in Caco-2 colon cancer cells
Biochem. J.
394
317-324
2006
Homo sapiens
Vogel, N.L.; Boeke, M.; Ashburner, B.P.
Spermidine/spermine N1-acetyltransferase 2 (SSAT2) functions as a coactivator for NF-kappaB and cooperates with CBP and P/CAF to enhance NF-kappaB-dependent transcription
Biochim. Biophys. Acta
1759
470-477
2006
Homo sapiens
Marverti, G.; Giuseppina Monti, M.; Pegg, A.E.; McCloskey, D.E.; Bettuzzi, S.; Ligabue, A.; Caporali, A.; DArca, D.; Moruzzi, M.S.
Spermidine/spermine N1-acetyltransferase transient overexpression restores sensitivity of resistant human ovarian cancer cells to N1,N12-bis(ethyl)spermine and to cisplatin
Carcinogenesis
26
1677-1686
2005
Homo sapiens
Babbar, N.; Hacker, A.; Huang, Y.; Casero, R.A.
Tumor necrosis factor alpha induces spermidine/spermine N1-acetyltransferase through nuclear factor kappaB in non-small cell lung cancer cells
J. Biol. Chem.
281
24182-24192
2006
Homo sapiens
Allen, W.L.; McLean, E.G.; Boyer, J.; McCulla, A.; Wilson, P.M.; Coyle, V.; Longley, D.B.; Casero, R.A.; Johnston, P.G.
The role of spermidine/spermine N1-acetyltransferase in determining response to chemotherapeutic agents in colorectal cancer cells
Mol. Cancer Ther.
6
128-137
2007
Homo sapiens
Bewley, M.C.; Graziano, V.; Jiang, J.; Matz, E.; Studier, F.W.; Pegg, A.E.; Coleman, C.S.; Flanagan, J.M.
Structures of wild-type and mutant human spermidine/spermine N1-acetyltransferase, a potential therapeutic drug target
Proc. Natl. Acad. Sci. USA
103
2063-2068
2006
Homo sapiens
Hegde, S.S.; Chandler, J.; Vetting, M.W.; Yu, M.; Blanchard, J.S.
Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase
Biochemistry
46
7187-7195
2007
Homo sapiens (P21673), Homo sapiens
Butcher, N.J.; Broadhurst, G.M.; Minchin, R.F.
Polyamine-dependent regulation of spermidine-spermine N1-acetyltransferase mRNA translation
J. Biol. Chem.
282
28530-28539
2007
Homo sapiens
Baek, J.H.; Liu, Y.V.; McDonald, K.R.; Wesley, J.B.; Zhang, H.; Semenza, G.L.
Spermidine/spermine N(1)-acetyltransferase-1 binds to hypoxia-inducible factor-1alpha (HIF-1alpha) and RACK1 and promotes ubiquitination and degradation of HIF-1alpha
J. Biol. Chem.
282
33358-33366
2007
Homo sapiens (P21673)
Simonian, A.; Khomutov, A.; Hyvonen, T.; Grigorenko, N.; Keinanen, T.; Vepsalainen, J.; Alhonen, L.; Janne, J.
Novel CoA-polyamine conjugates for effective inhibition of spermine/spermidine-N1-acetyltransferase
Nucleosides Nucleotides Nucleic Acids
26
1245-1248
2007
Homo sapiens (P21673)
Klempan, T.; Rujescu, D.; Mérette, C.; Himmelman, C.; Sequeira, A.; Canetti, L.; Fiori, L.; Schneider, B.; Bureau, A.; Turecki, G.
Profiling brain expression of the spermidine/spermine N1-acetyltransferase 1 (SAT1) gene in suicide
Am. J. Med. Genet. B Neuropsychiatr. Genet.
150
934-943
2009
Homo sapiens
Pegg, A.
Spermidine/spermine-N1-acetyltransferase: A key metabolic regulator
Am. J. Physiol. Endocrinol. Metab.
294
995-1010
2008
Homo sapiens, Mus musculus, Rattus norvegicus
Fiori, L.M.; Mechawar, N.; Turecki, G.
Identification and characterization of spermidine/spermine N1-acetyltransferase promoter variants in suicide completers
Biol. Psychiatry
66
460-467
2009
Homo sapiens
Liu, B.; Sun, H.; Wang, W.; Li, W.; Yan, Y.F.; Chen, S.M.; Yang, Y.P.; Xu, C.X.; Xin, J.X.; Liu, X.X.
Adenovirus vector-mediated upregulation of spermidine /spermine N1-acetyltransferase impairs human gastric cancer growth in vitro and in vivo
Cancer Sci.
100
2126-2132
2009
Homo sapiens
Holst, C.; Nevsten, P.; Johansson, F.; Carlemalm, E.; Oredsson, S.
Subcellular distribution of spermidine/spermine N1-acetyltransferase
Cell Biol. Int.
32
39-47
2008
Homo sapiens
Marverti, G.; Ligabue, A.; Guerrieri, D.; Paglietti, G.; Piras, S.; Costi, M.P.; Farina, D.; Frassineti, C.; Monti, M.G.; Moruzzi, M.S.
Spermidine/spermine N1-acetyltranferase modulation by novel folate cycle inhibitors in cisplatin-sensitive and -resistant human ovarian cancer cell lines
Gynecol. Oncol.
117
202-210
2009
Homo sapiens
Kramer, D.; Diegelman, P.; Jell, J.; Vujcic, S.; Merali, S.; Porter, C.
Polyamine acetylation modulates polyamine metabolic flux, a prelude to broader metabolic consequences
J. Biol. Chem.
283
4241-4251
2008
Homo sapiens
Sun, H.; Liu, B.; Wang, W.; Jiang, G.S.; Li, W.; Yang, Y.P.; Xu, C.X.; Yan, Y.F.; Liu, X.X.
Adenovirus-mediated expression of spermidine/spermine N1-acetyltransferase gene induces S-phase arrest in human colorectal cancer cells
Oncol. Rep.
20
1229-1235
2008
Homo sapiens
Stanic, I.; Facchini, A.; Borzi, R.; Stefanelli, C.; Flamigni, F.
The polyamine analogue N1,N11-diethylnorspermine can induce chondrocyte apoptosis independently of its ability to alter metabolism and levels of natural polyamines
J. Cell. Physiol.
219
109-116
2009
Homo sapiens
Lee, S.B.; Park, J.H.; Folk, J.E.; Deck, J.A.; Pegg, A.E.; Sokabe, M.; Fraser, C.S.; Park, M.H.
Inactivation of eukaryotic initiation factor 5A (eIF5A) by specific acetylation of its hypusine residue by spermidine/spermine acetyltransferase 1 (SSAT1)
Biochem. J.
433
205-213
2011
Homo sapiens (P21673)
Neidhart, M.; Karouzakis, E.; Juengel, A.; Gay, R.E.; Gay, S.
Inhibition of spermidine/spermine N1-acetyltransferase activity: a new therapeutic concept in rheumatoid arthritis
Arthritis Rheumatol.
66
1723-1733
2014
Homo sapiens (P21673), Homo sapiens
Mandal, S.; Mandal, A.; Park, M.H.
Depletion of the polyamines spermidine and spermine by overexpression of spermidine/spermine N1-acetyltransferase 1 (SAT1) leads to mitochondria-mediated apoptosis in mammalian cells
Biochem. J.
468
435-447
2015
Homo sapiens (P21673)
Hyvoenen, M.; Weisell, J.; Khomutov, A.; Alhonen, L.; Vepsaelaeinen, J.; Keinaenen, T.
Metabolism of triethylenetetramine and 1,12-diamino-3,6,9-triazadodecane by the spermidine/spermine-N1-acetyltransferase and thialysine acetyltransferase
Drug Metab. Dispos.
41
30-32
2013
Homo sapiens (P21673), Homo sapiens, Mus musculus (P48026)
Squassina, A.; Manchia, M.; Chillotti, C.; Deiana, V.; Congiu, D.; Paribello, F.; Roncada, P.; Soggiu, A.; Piras, C.; Urbani, A.; Robertson, G.S.; Keddy, P.; Turecki, G.; Rouleau, G.A.; Alda, M.; Del Zompo, M.
Differential effect of lithium on spermidine/spermine N1-acetyltransferase expression in suicidal behaviour
Int. J. Neuropsychopharmacol.
16
2209-2218
2013
Homo sapiens (P21673)
Lien, Y.C.; Ou, T.Y.; Lin, Y.T.; Kuo, P.C.; Lin, H.J.
Duplication and diversification of the spermidine/spermine N1-acetyltransferase 1 genes in zebrafish
PLoS ONE
8
e54017
2013
Danio rerio (Q6GQM2), Danio rerio, Homo sapiens (P21673), Homo sapiens
Keinanen, T.; Hyvonen, T.; Vepsalainen, J.; Alhonen, L.; Khomutov, A.; Janne, J.
Stable analogues of coenzyme-substrate complex of spermidine/spermine-N 1-acetyltransferase reaction. Synthesis and interaction with the enzyme
Russ. J. Bioorg. Chem.
40
155-161
2014
Homo sapiens (P21673)
-
Mounce, B.C.; Poirier, E.Z.; Passoni, G.; Simon-Loriere, E.; Cesaro, T.; Prot, M.; Stapleford, K.A.; Moratorio, G.; Sakuntabhai, A.; Levraud, J.P.; Vignuzzi, M.
Interferon-induced spermidine-spermine acetyltransferase and polyamine depletion restrict Zika and chikungunya viruses
Cell Host Microbe
20
167-177
2016
Homo sapiens
Maksymiuk, A.W.; Sitar, D.S.; Ahmed, R.; Cheng, B.; Bach, H.; Bagchi, R.A.; Aroutiounova, N.; Tappia, P.S.; Ramjiawan, B.
Spermidine/spermine N1-acetyltransferase-1 as a diagnostic biomarker in human cancer
Future Sci. OA
4
FSO345
2018
Homo sapiens
Thakur, V.S.; Aguila, B.; Brett-Morris, A.; Creighton, C.J.; Welford, S.M.
Spermidine/spermine N1-acetyltransferase 1 is a gene-specific transcriptional regulator that drives brain tumor aggressiveness
Oncogene
38
6794-6800
2019
Homo sapiens
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.
Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasis via AKT/beta-catenin signaling pathways in hepatocellular and colorectal carcinoma cells
Oncotarget
8
1092-1109
2017
Homo sapiens
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