SAT2

Summary

SAT2 (spermidine/spermine N1-acetyltransferase family member 2, HGNC:23160) is a protein-coding gene on chromosome 17p13.1, encoding Thialysine N-epsilon-acetyltransferase (Q96F10). Catalyzes the N-acetylation of the amino acid thialysine (S-(2-aminoethyl)-L-cysteine), a L-lysine analog with the 4-methylene group substituted with a sulfur.

Enables diamine N-acetyltransferase activity and identical protein binding activity. Involved in polyamine metabolic process. Located in extracellular exosome.

Source: NCBI Gene 112483 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 26 total
• Druggable target: yes
• MANE Select transcript: NM_133491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23160
Approved symbol	SAT2
Name	spermidine/spermine N1-acetyltransferase family member 2
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	SSAT2
Ensembl gene	ENSG00000141504
Ensembl biotype	protein_coding
OMIM	611463
Entrez	112483

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 9 protein_coding, 7 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000269298, ENST00000380466, ENST00000570850, ENST00000570914, ENST00000571074, ENST00000571195, ENST00000572224, ENST00000573566, ENST00000573930, ENST00000575114, ENST00000575826, ENST00000576579, ENST00000576686, ENST00000576846, ENST00000857010, ENST00000857011, ENST00000857012, ENST00000857013, ENST00000925532, ENST00000925533, ENST00000966241

RefSeq mRNA: 4 — MANE Select: NM_133491 NM_001320845, NM_001320846, NM_001320847, NM_133491

CCDS: CCDS11116, CCDS82055

Canonical transcript exons

ENST00000269298 — 6 exons

Exon	Start	End
ENSE00001061697	7626234	7626614
ENSE00002667862	7627570	7627821
ENSE00003490538	7626753	7626793
ENSE00003516769	7626943	7627044
ENSE00003587952	7627363	7627414
ENSE00003620369	7627143	7627226

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 99.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.7123 / max 213.4445, expressed in 1751 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164266	34.7123	1751

Top tissues by expression

259 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	99.30	gold quality
right adrenal gland cortex	UBERON:0035827	99.28	gold quality
right adrenal gland	UBERON:0001233	99.16	gold quality
adrenal cortex	UBERON:0001235	99.09	gold quality
left adrenal gland cortex	UBERON:0035825	99.09	gold quality
left adrenal gland	UBERON:0001234	99.08	gold quality
jejunal mucosa	UBERON:0000399	98.98	gold quality
right lobe of liver	UBERON:0001114	98.95	gold quality
ileal mucosa	UBERON:0000331	98.89	gold quality
duodenum	UBERON:0002114	98.86	gold quality
adrenal gland	UBERON:0002369	98.72	gold quality
adult mammalian kidney	UBERON:0000082	98.64	gold quality
left ovary	UBERON:0002119	98.55	gold quality
right ovary	UBERON:0002118	98.44	gold quality
adenohypophysis	UBERON:0002196	98.41	gold quality
body of pancreas	UBERON:0001150	98.29	gold quality
pituitary gland	UBERON:0000007	98.27	gold quality
liver	UBERON:0002107	98.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.01	gold quality
right frontal lobe	UBERON:0002810	98.00	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.00	gold quality
small intestine	UBERON:0002108	97.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.93	gold quality
metanephros cortex	UBERON:0010533	97.91	gold quality
cortex of kidney	UBERON:0001225	97.86	gold quality
cerebellar hemisphere	UBERON:0002245	97.74	gold quality
renal medulla	UBERON:0000362	97.73	gold quality
cerebellar cortex	UBERON:0002129	97.72	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.69	gold quality
left lobe of thyroid gland	UBERON:0001120	97.63	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	77.32
E-HCAD-10	yes	29.62
E-GEOD-134144	yes	29.52
E-CURD-112	yes	18.10
E-ANND-3	yes	16.52
E-GEOD-135922	yes	9.91
E-MTAB-9801	yes	6.31
E-MTAB-6524	no	176.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting SAT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-6828-3P	96.06	67.61	1155

Literature-anchored findings (GeneRIF, showing 5)

• Crystallization of this protein and its recombinant form and its complexation with coenzyme A. (PMID:16596569)
• The expression of three messengers coding for SAT-1, SAT-2 and GalNAcT-1 in human samples of intestinal cancer and some cell lines (breast cancer and melanomas), was evaluated. (PMID:17119850)
• SSAT2 is an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1alpha (PMID:17558023)
• SSAT1, which shares 46% amino acid identity with SSAT2, also binds to HIF-1alpha and promotes its ubiquitination/degradation. However, in contrast to SSAT2, SSAT1 acts by stabilizing the interaction of HIF-1alpha with RACK1 (PMID:17875644)
• expression of SSAT mediated by Ad-SSAT infection inhibits the growth of colorectal cancer cells (PMID:18949426)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sat2	ENSMUSG00000069835
rattus_norvegicus	Sat2	ENSRNOG00000011714
drosophila_melanogaster	CG4210	FBGN0038302
caenorhabditis_elegans		WBGENE00008408

Paralogs (2): SAT1 (ENSG00000130066), SATL1 (ENSG00000184788)

Protein

Protein identifiers

Thialysine N-epsilon-acetyltransferase — Q96F10 (reviewed: Q96F10)

Alternative names: Diamine acetyltransferase 2, Spermidine/spermine N(1)-acetyltransferase 2

All UniProt accessions (3): I3L0W4, I3L2W7, Q96F10

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the N-acetylation of the amino acid thialysine (S-(2-aminoethyl)-L-cysteine), a L-lysine analog with the 4-methylene group substituted with a sulfur. May also catalyze acetylation of polyamines, such as norspermidine, spermidine or spermine. However, ability to acetylate polyamines is weak, suggesting that it does not act as a diamine acetyltransferase in vivo.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed. Under physiological conditions, SSAT2 is expressed at lower level that SSAT1 (SSAT). Many tissues express only SSAT1, several tissues express both SSAT1 and SSAT2, and bone, cervix, ovary and pineal gland expressed only SSAT2.

Induction. Not inducible by polyamine analogs.

Similarity. Belongs to the acetyltransferase family.

RefSeq proteins (4): NP_001307774, NP_001307775, NP_001307776, NP_597998* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000182	GNAT_dom	Domain
IPR016181	Acyl_CoA_acyltransferase	Homologous_superfamily
IPR051016	Diverse_Substrate_AcTransf	Family

Pfam: PF00583

Enzyme classification (BRENDA):

• EC 2.3.1.57 — diamine N-acetyltransferase (BRENDA: 27 organisms, 270 substrates, 52 inhibitors, 104 Km, 34 kcat entries)

Substrate kinetics (BRENDA)

26 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SPERMIDINE	0.022–4	25
SPERMINE	0.0037–1.7	25
ACETYL-COA	0.0015–0.35	11
1,3-DIAMINOPROPANE	0.107–20.6	5
PUTRESCINE	0.25–25.3	5
SYM-NORSPERMIDINE	0.008–0.5	3
1,5-DIAMINOPENTANE	0.1–0.44	2
L-LYSINE	6.1–8	2
L-ORNITHINE	2.4–2.6	2
MALONYL-COA	0.186–0.264	2
N1-ACETYLSPERMINE	0.03–0.295	2
1,12-DIAMINO-3,6,9-TRIAZADODECANE	0.106	1
1,6-DIAMINOHEXANE	0.4	1
1,7-DIAMINOHEPTANE	1.59	1
15-DEOXYSPERGUALIN	0.012	1

Catalyzed reactions (Rhea), 2 shown:

• an alkane-alpha,omega-diamine + acetyl-CoA = an N-acetylalkane-alpha,omega-diamine + CoA + H(+) (RHEA:11116)
• S-(2-aminoethyl)-L-cysteine + acetyl-CoA = S-(2-acetamidoethyl)-L-cysteine + CoA + H(+) (RHEA:64804)

UniProt features (30 total): helix 9, strand 8, binding site 7, chain 1, domain 1, modified residue 1, sequence variant 1, active site 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2BEI	X-RAY DIFFRACTION	1.84
2Q4V	X-RAY DIFFRACTION	1.84

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96F10-F1	94.25	0.92

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 140 (proton donor)

Ligand- & substrate-binding residues (7): 27–28; 92; 94–96; 102–107; 133–135; 140; 152

Post-translational modifications (1): 29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 0 (showing top):

GO Biological Process (4): obsolete spermidine acetylation (GO:0032918), obsolete spermine acetylation (GO:0032919), obsolete putrescine acetylation (GO:0032920), nor-spermidine metabolic process (GO:0046204)

GO Molecular Function (7): diamine N-acetyltransferase activity (GO:0004145), N-acetyltransferase activity (GO:0008080), identical protein binding (GO:0042802), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (2): cytoplasm (GO:0005737), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
polyamine metabolic process	1
N-acetyltransferase activity	1
acetyltransferase activity	1
protein binding	1
binding	1
catalytic activity	1
transferase activity	1
acyltransferase activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

582 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAT2	PAOX	Q6QHF9	895
SAT2	ELOC	Q15369	870
SAT2	GLYATL1	Q969I3	800
SAT2	HIF1A	Q16665	749
SAT2	EGLN1	Q9GZT9	682
SAT2	RACK1	P25388	667
SAT2	CUL2	Q13617	638
SAT2	VHL	P40337	603
SAT2	ELOB	Q15370	599
SAT2	RBX1	P62877	567
SAT2	NAA38	Q9BRA0	471
SAT2	MCM7	P33993	465
SAT2	OS9	Q13438	447
SAT2	SRM	P19623	435
SAT2	SAT1	P21673	387

IntAct

22 interactions, top by confidence:

A	B	Type	Score
PPIL1	SNW1	psi-mi:“MI:0914”(association)	0.930
SAT1	SAT2	psi-mi:“MI:0915”(physical association)	0.800
SAT2	SAT2	psi-mi:“MI:0915”(physical association)	0.740
NRBP1	TBC1D4	psi-mi:“MI:0914”(association)	0.530
SAT2	C1QBP	psi-mi:“MI:0915”(physical association)	0.400
SAT2	NDUFA10	psi-mi:“MI:0915”(physical association)	0.400
SAT2	SMC1A	psi-mi:“MI:0915”(physical association)	0.400
SAT2	PANK2	psi-mi:“MI:0915”(physical association)	0.400
NLRP12	SAT2	psi-mi:“MI:0915”(physical association)	0.370
SAT2	SMR3B	psi-mi:“MI:0914”(association)	0.350
SAT2	POTEF	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
SAT2	SAT2	psi-mi:“MI:0915”(physical association)	0.000
SAT2	SAT1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): SAT2 (Two-hybrid), SAT2 (Two-hybrid), PANK2 (Affinity Capture-MS), SAT2 (Two-hybrid), SAT2 (Two-hybrid), SAT2 (Proximity Label-MS), SAT2 (Proximity Label-MS), SAT2 (Proximity Label-MS), SAT2 (Affinity Capture-MS), SAT2 (Affinity Capture-MS), SAT2 (Affinity Capture-MS), PANK2 (Affinity Capture-MS), SAT2 (Affinity Capture-MS), SAT2 (Affinity Capture-MS), POTEF (Affinity Capture-MS)

ESM2 similar proteins: A0A077ES70, A0A077ESS0, A0A077EYL8, A3DBL4, A8A3I7, A9MFX6, B1IUW9, B1XCN7, B4EY59, O07579, O17731, O27404, O31581, O32075, O94340, P21673, P39979, P40586, P46543, P46854, P48026, P49431, P79081, P93711, P96084, P96579, Q01612, Q06592, Q28999, Q31X74, Q3T0Q0, Q3YYF4, Q43161, Q46877, Q5PF19, Q5UPZ9, Q63ZT8, Q6GNL7, Q6P8J2, Q7PCJ8

Diamond homologs: O05517, O74311, P0A944, P0A945, P0A946, P0A947, P44305, Q4JBG0, Q7PCJ8, Q7PCJ9, Q8ZJW4, Q95RC0, Q96F10, Q976C3, Q980R9, O17731, P79081, P80969, Q6P8J2, Q9SMB8, Q9ZV05, Q9ZV06, A0LWI8, O29729, P16691, Q58604, Q8ZKE6, C1ATC6, I6YG32, O34376, P08457, P37506, Q49857, Q9QXS8, Q9UHF3, P21673, P48026, P49431, Q01612, Q28999

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

26 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1098 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7627207:A:C	F46L	0.981
17:7627207:A:T	F46L	0.981
17:7627209:A:G	F46L	0.981
17:7626970:C:G	D93H	0.975
17:7626969:T:A	D93V	0.972
17:7626960:A:T	V96E	0.964
17:7626969:T:G	D93A	0.964
17:7627001:A:C	S82R	0.963
17:7627001:A:T	S82R	0.963
17:7627003:T:G	S82R	0.963
17:7626968:A:C	D93E	0.961
17:7626968:A:T	D93E	0.961
17:7627400:G:C	F27L	0.960
17:7627400:G:T	F27L	0.960
17:7627402:A:G	F27L	0.960
17:7627024:C:A	G75W	0.958
17:7626945:C:G	R101P	0.957
17:7626972:T:A	E92V	0.955
17:7627029:C:T	G73D	0.950
17:7627397:T:A	E28D	0.950
17:7627397:T:G	E28D	0.950
17:7627023:C:T	G75E	0.947
17:7626562:T:A	N133I	0.946
17:7627183:A:C	C54W	0.945
17:7627211:C:T	G45D	0.941
17:7626758:C:G	A114P	0.940
17:7627024:C:G	G75R	0.940
17:7627024:C:T	G75R	0.940
17:7626583:C:G	R126P	0.937
17:7627185:A:G	C54R	0.937

dbSNP variants (sampled 300 via entrez): RS1000367065 (17:7629760 T>C), RS1001483022 (17:7628374 C>T), RS1002271599 (17:7629177 A>G), RS1002375114 (17:7627313 C>T), RS1002387688 (17:7628996 C>T), RS1002484503 (17:7626887 C>G,T), RS1002835624 (17:7625806 A>C,G), RS1004289332 (17:7629840 G>A,C), RS1005178341 (17:7628774 G>T), RS1006137324 (17:7628384 C>T), RS1007139754 (17:7629537 C>A,T), RS1007192143 (17:7629838 A>G), RS1007293488 (17:7625922 G>A), RS1009485589 (17:7626873 G>A,C), RS1009750552 (17:7629466 T>C)

Disease associations

OMIM: gene MIM:611463 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001554_1	Sex hormone-binding globulin levels	2.000000e-16
GCST010703_158	Brain morphology (MOSTest)	3.000000e-09
GCST012020_477	Serum metabolite levels	1.000000e-38

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004696	sex hormone-binding globulin measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3509592 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	8
bisphenol A	affects expression, decreases methylation, increases expression	3
trichostatin A	decreases expression, affects cotreatment	2
sodium arsenite	increases expression	2
Estradiol	decreases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
beta-lapachone	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cupric chloride	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
epigallocatechin gallate	affects cotreatment, increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Benzo(a)pyrene	increases expression	1
Carbamazepine	affects expression	1
Dactinomycin	increases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, decreases expression	1
Diclofenac	affects expression	1
Diuron	decreases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3538523	ADMET	Drug level in human HepG2 cells assessed as SSAT2-mediated compound formation treated with TETA at 1 mM for 24 hrs pretreated with 50 uM DENSpm for 24 hrs	Metabolism of triethylenetetramine and 1,12-diamino-3,6,9-triazadodecane by the spermidine/spermine-N(1)-acetyltransferase and thialysine acetyltransferase. — Drug Metab Dispos

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TK03	HAP1 SAT2 (-) 1	Cancer cell line	Male
CVCL_XS42	HAP1 SAT2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.