P21673 (SAT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Diamine acetyltransferase 1
EC=2.3.1.57

Alternative name(s):
Polyamine N-acetyltransferase 1
Putrescine acetyltransferase
Spermidine/spermine N(1)-acetyltransferase 1
Short name=SSAT
Short name=SSAT-1

Gene names

Name:	SAT1
Synonyms:	SAT

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	171 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Enzyme which catalyzes the acetylation of polyamines. Substrate specificity: norspermidine = spermidine >> spermine > N(1)-acetylspermine > putrescine. This highly regulated enzyme allows a fine attenuation of the intracellular concentration of polyamines. Also involved in the regulation of polyamine transport out of cells. Acts on 1,3-diaminopropane, 1,5-diaminopentane, putrescine, spermidine (forming N(1)- and N(8)-acetylspermidine), spermine, N(1)-acetylspermidine and N(8)-acetylspermidine.
Catalytic activity	Acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine.
Pathway	Amine and polyamine degradation; putrescine degradation; N-acetylputrescine from putrescine: step 1/1.
Subunit structure	Homodimer. Ref.8 Ref.10
Subcellular location	Cytoplasm.
Involvement in disease	Keratosis follicularis spinulosa decalvans X-linked (KFSDX) [MIM:308800]: A rare disorder affecting the skin and the eye. Affected men show thickening of the skin of the neck, ears, and extremities, especially the palms and soles, loss of eyebrows, eyelashes and beard, thickening of the eyelids with blepharitis and ectropion, and corneal degeneration. Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12
Sequence similarities	Belongs to the acetyltransferase family. Contains 1 N-acetyltransferase domain.
Biophysicochemical properties	Kinetic parameters: KM=3.8 µM for acetyl-coenzyme A Ref.9 KM=5.7 µM for spermine KM=22 µM for spermidine pH dependence: Optimum pH is 8.0.

Ontologies

Keywords
Cellular component	Cytoplasm
Molecular function	Acyltransferase Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from expression pattern PubMed 11866539. Source: UniProtKB polyamine biosynthetic process Traceable author statement. Source: Reactome putrescine catabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway regulation of cell proliferation Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	diamine N-acetyltransferase activity Traceable author statement Ref.1. Source: ProtInc spermidine binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HOXB9	P17482	3	EBI-711613,EBI-745290
TCF25	Q9BQ70	3	EBI-711613,EBI-745182

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 171

171

Diamine acetyltransferase 1

PRO_0000074591

Regions

Domain

4 – 171

168

N-acetyltransferase

Region

27 – 28

2

Substrate binding

Region

94 – 96

3

Acetyl-CoA binding

Region

102 – 107

6

Acetyl-CoA binding

Region

126 – 128

3

Substrate binding

Region

133 – 136

4

Acetyl-CoA binding

Region

140 – 143

4

Acetyl-CoA binding

Sites

Binding site

92

1

Substrate; via carbonyl oxygen

Binding site

152

1

Substrate

Experimental info

Mutagenesis

140

1

Y → F: Reduces activity by 95%. Ref.8

Sequence conflict

26

1

K → E in CAA78509. Ref.3

Sequence conflict

26

1

K → E in AAA98854. Ref.4

Sequence conflict

69

1

H → G AA sequence Ref.7

Sequence conflict

84

1

W → P AA sequence Ref.7

Secondary structure

1

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171

Helix Strand Turn

Details...

Beta strand

5 – 8

4

Helix

11 – 13

3

Helix

14 – 26

13

Beta strand

28 – 30

3

Helix

31 – 33

3

Helix

38 – 45

8

Beta strand

47 – 49

3

Beta strand

53 – 58

6

Helix

61 – 63

3

Beta strand

71 – 82

12

Turn

83 – 85

3

Beta strand

86 – 96

11

Helix

98 – 100

3

Beta strand

102 – 104

3

Helix

105 – 120

16

Beta strand

123 – 130

8

Helix

134 – 141

8

Turn

142 – 144

3

Helix

148 – 152

5

Beta strand

154 – 160

7

Helix

161 – 168

8

Sequences

	Sequence		Length	Mass (Da)
	P21673 [UniParc]. Last modified May 1, 1991. Version 1. Checksum: 6A0578B88CD72F09	FASTA	171	20,024
	10 20 30 40 50 60 MAKFVIRPAT AADCSDILRL IKELAKYEYM EEQVILTEKD LLEDGFGEHP FYHCLVAEVP 70 80 90 100 110 120 KEHWTPEGHS IVGFAMYYFT YDPWIGKLLY LEDFFVMSDY RGFGIGSEIL KNLSQVAMRC 130 140 150 160 170 RCSSMHFLVA EWNEPSINFY KRRGASDLSS EEGWRLFKID KEYLLKMATE E

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a cDNA clone that codes for human spermidine/spermine N1-acetyltransferase." Casero R.A. Jr., Celano P., Ervin S.J., Applegren N.B., Wiest L., Pegg A.E. J. Biol. Chem. 266:810-814(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Characterization of a full-length cDNA which codes for the human spermidine/spermine N1-acetyltransferase." Xiao L., Celano P., Mank A.R., Pegg A.E., Casero R.A. Jr. Biochem. Biophys. Res. Commun. 179:407-415(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[3]	"Structure of the human spermidine/spermine N1-acetyltransferase gene (exon/intron gene organization and localization to Xp22.1)." Xiao L., Celano P., Mank A.R., Griffin C., Wang J.E., Casero R.A. Jr. Biochem. Biophys. Res. Commun. 187:1493-1502(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Differential transcription of the human spermidine/spermine N1-acetyltransferase (SSAT) gene in human lung carcinoma cells." Xiao L., Casero R.A. Jr. Biochem. J. 313:691-696(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow and Skin.
[7]	"High specific induction of spermidine/spermine N1-acetyltransferase in a human large cell lung carcinoma." Casero R.A. Jr., Celano P., Ervin S.J., Wiest L., Pegg A.E. Biochem. J. 270:615-620(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE.
[8]	"Structures of wild-type and mutant human spermidine/spermine N1-acetyltransferase, a potential therapeutic drug target." Bewley M.C., Graziano V., Jiang J., Matz E., Studier F.W., Pegg A.E., Coleman C.S., Flanagan J.M. Proc. Natl. Acad. Sci. U.S.A. 103:2063-2068(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEXES WITH ACETYL-COENZYME A; SPERMINE AND N1,N11-BIS-(ETHYL)-NORSPERMINE, MUTAGENESIS OF TYR-140, SUBUNIT.
[9]	"Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase." Hegde S.S., Chandler J., Vetting M.W., Yu M., Blanchard J.S. Biochemistry 46:7187-7195(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH N1-SPERMINE-ACETYL-COENZYME A, BIOPHYSICOCHEMICAL PROPERTIES.
[10]	"Crystal structure of human spermidine/spermine N1-acetyltransferase (hSSAT): the first structure of a new sequence family of transferase homologous superfamily." Zhu Y.-Q., Zhu D.-Y., Yin L., Zhang Y., Vonrhein C., Wang D.-C. Proteins 63:1127-1131(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), SUBUNIT.
[11]	"Molecular genetic analysis of two families with keratosis follicularis spinulosa decalvans: refinement of gene localization and evidence for genetic heterogeneity." Oosterwijk J.C., Richard G., van der Wielen M.J.R., van de Vosse E., Harth W., Sandkuijl L.A., Bakker E., van Ommen G.-J.B. Hum. Genet. 100:520-524(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN KFSDX.
[12]	"Gene dosage of the spermidine/spermine N(1)-acetyltransferase (SSAT) gene with putrescine accumulation in a patient with a Xp21.1p22.12 duplication and keratosis follicularis spinulosa decalvans (KFSD)." Gimelli G., Giglio S., Zuffardi O., Alhonen L., Suppola S., Cusano R., Lo Nigro C., Gatti R., Ravazzolo R., Seri M. Hum. Genet. 111:235-241(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN KFSDX.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M77693 mRNA. Translation: AAA60573.1.
M55580 mRNA. Translation: AAA63260.1.
Z14136 Genomic DNA. Translation: CAA78509.1.
U40369 Genomic DNA. Translation: AAA98854.1.
BT006825 mRNA. Translation: AAP35471.1.
BC002503 mRNA. Translation: AAH02503.1.
BC008424 mRNA. Translation: AAH08424.1.

IPI

IPI00009889.

PIR

JH0783.

RefSeq

NP_002961.1. NM_002970.2.

UniGene

Hs.28491.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2B3U	X-ray	1.85	A/B	1-171	[»]
2B3V	X-ray	1.95	A	1-171	[»]
2B4B	X-ray	2.00	A/B	1-171	[»]
2B4D	X-ray	2.00	A/B	1-171	[»]
2B58	X-ray	1.95	A	1-171	[»]
2B5G	X-ray	1.70	A/B	1-171	[»]
2F5I	X-ray	2.30	A/B	1-171	[»]
2FXF	X-ray	2.00	A/B	2-171	[»]
2G3T	X-ray	1.80	A/B	1-171	[»]
2JEV	X-ray	2.30	A/B	1-171	[»]

ProteinModelPortal

P21673.

ModBase

Search...

Protein-protein interaction databases

IntAct

P21673. 58 interactions.

MINT

MINT-1369180.

STRING

9606.ENSP00000368572.

PTM databases

PhosphoSite

P21673.

Polymorphism databases

DMDM

114322.

Proteomic databases

PaxDb

P21673.

PRIDE

P21673.

Protocols and materials databases

DNASU

6303.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000379270; ENSP00000368572; ENSG00000130066.

GeneID

6303.

KEGG

hsa:6303.

UCSC

uc004dau.3. human.

Organism-specific databases

CTD

6303.

GeneCards

GC0XP023802.

H-InvDB

HIX0176797.

HGNC

HGNC:10540. SAT1.

HPA

CAB047343.

MIM

308800. phenotype.
313020. gene.

neXtProt

NX_P21673.

Orphanet

2340. Keratosis follicularis spinulosa decalvans.

PharmGKB

PA162402389.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0454.

HOGENOM

HOG000078521.

HOVERGEN

HBG063175.

KO

K00657.

OrthoDB

EOG4NGGNW.

Enzyme and pathway databases

BioCyc

MetaCyc:HS05339-MONOMER.

BRENDA

2.3.1.57. 2681.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00188; UER00363.

Gene expression databases

ArrayExpress

P21673.

Bgee

P21673.

CleanEx

HS_SAT1.

Genevestigator

P21673.

GermOnline

ENSG00000130066. Homo sapiens.

Family and domain databases

Gene3D

3.40.630.30. 1 hit.

InterPro

IPR016181. Acyl_CoA_acyltransferase.
IPR000182. GNAT_dom.
[Graphical view]

Pfam

PF00583. Acetyltransf_1. 1 hit.
[Graphical view]

SUPFAM

SSF55729. Acyl_CoA_acyltransferase. 1 hit.

PROSITE

PS51186. GNAT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P21673.

ChEMBL

CHEMBL4286.

ChiTaRS

SAT1. human.

DrugBank

DB00127. Spermine.

EvolutionaryTrace

P21673.

GenomeRNAi

6303.

NextBio

24471.

SOURCE

Search...

Entry information

Entry name

SAT1_HUMAN

Accession

Primary (citable) accession number: P21673

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	May 1, 1991
Last modified:	May 1, 2013
This is version 134 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.