P53686 (HST2_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NAD-dependent protein deacetylase HST2
EC=3.5.1.-

Alternative name(s):
Homologous to SIR2 protein 2
Regulatory protein SIR2 homolog 2

Gene names

Name:	HST2
Ordered Locus Names:	YPL015C
ORF Names:	LPA2C

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	357 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	NAD-dependent histone deacetylase that is involved in nuclear silencing events. Derepresses subtelomeric silencing and increases repression in nucleolar (rDNA) silencing. Its function is negatively regulated by active nuclear export. Ref.5 Ref.6 Ref.7 Ref.10 Ref.11
Catalytic activity	NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. Ref.12
Cofactor	Binds 1 zinc ion per subunit.
Enzyme regulation	Inhibited by ADP-ribose and nicotinamide. Ref.12
Subunit structure	Homotrimer. Monomer. Homotrimeric in its unliganded state. Undergoes a trimer-monomer transition upon acetyl-lysine substrate binding. Ref.16
Subcellular location	Cytoplasm. Nucleus. Note: Shuttles between the nucleus and cytoplasm, but is largely cytoplasmic owing to efficient nuclear export. Nuclear exclusion is mediated by the exportin CRM1. Ref.7 Ref.8 Ref.11
Miscellaneous	Present with 5260 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the sirtuin family. Class I subfamily. Contains 1 deacetylase sirtuin-type domain.
Biophysicochemical properties	Kinetic parameters: KM=10.2 µM for NAD+ Ref.6 Ref.10 Ref.12 Ref.18 KM=0.92 µM for acetylated poly-L-lysine KM=0.5 µM for a synthetic histone H3K14 acetyllysine peptide

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	Metal-binding NAD Zinc
Molecular function	Hydrolase Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chromatin silencing at rDNA Inferred from mutant phenotype Ref.7PubMed 16051752. Source: SGD chronological cell aging Inferred from mutant phenotype PubMed 16051752. Source: SGD negative regulation of chromatin silencing at telomere Inferred from mutant phenotype Ref.7. Source: SGD negative regulation of mitotic recombination Inferred from mutant phenotype PubMed 16051752. Source: SGD transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay Ref.7. Source: SGD nucleus Inferred from direct assay Ref.11. Source: SGD
Molecular_function	NAD+ binding Inferred from electronic annotation. Source: InterPro NAD-dependent histone deacetylase activity Inferred from direct assay Ref.5. Source: SGD zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 357

357

NAD-dependent protein deacetylase HST2

PRO_0000110282

Regions

Domain

13 – 286

274

Deacetylase sirtuin-type

Nucleotide binding

32 – 52

21

NAD

Nucleotide binding

115 – 118

4

NAD

Nucleotide binding

223 – 225

3

NAD

Nucleotide binding

248 – 250

3

NAD

Sites

Active site

135

1

Proton acceptor Ref.14

Metal binding

143

1

Zinc

Metal binding

146

1

Zinc

Metal binding

170

1

Zinc

Metal binding

173

1

Zinc

Binding site

270

1

NAD; via amide nitrogen

Amino acid modifications

Modified residue

340

1

Phosphoserine Ref.13

Experimental info

Mutagenesis

117

1

I → A, D, H, W or Y: Nearly or completely catalytically inactive. Ref.18

Mutagenesis

117

1

I → F or V: Near wild-type activity for deacetylation. Increases slightly the KM for NAD(+) to 25 uM. Ref.18

Secondary structure

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357

Helix Strand Turn

Details...

Beta strand

3 – 6

4

Helix

9 – 21

13

Beta strand

27 – 31

5

Helix

33 – 39

7

Beta strand

44 – 46

3

Turn

47 – 49

3

Helix

51 – 53

3

Helix

56 – 58

3

Helix

63 – 67

5

Helix

69 – 74

6

Helix

77 – 86

10

Beta strand

88 – 90

3

Helix

95 – 105

11

Beta strand

109 – 114

6

Helix

120 – 123

4

Helix

128 – 130

3

Beta strand

131 – 133

3

Beta strand

136 – 143

8

Turn

144 – 146

3

Helix

153 – 159

7

Beta strand

161 – 163

3

Turn

171 – 173

3

Beta strand

176 – 181

6

Helix

191 – 208

18

Beta strand

218 – 223

6

Turn

230 – 232

3

Helix

233 – 237

5

Beta strand

242 – 250

9

Helix

254 – 257

4

Beta strand

264 – 266

3

Helix

270 – 281

12

Helix

284 – 291

8

Helix

304 – 313

10

Sequences

	Sequence		Length	Mass (Da)
	P53686 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: ED281E5B8241A4D0	FASTA	357	39,979
	10 20 30 40 50 60 MSVSTASTEM SVRKIAAHMK SNPNAKVIFM VGAGISTSCG IPDFRSPGTG LYHNLARLKL 70 80 90 100 110 120 PYPEAVFDVD FFQSDPLPFY TLAKELYPGN FRPSKFHYLL KLFQDKDVLK RVYTQNIDTL 130 140 150 160 170 180 ERQAGVKDDL IIEAHGSFAH CHCIGCGKVY PPQVFKSKLA EHPIKDFVKC DVCGELVKPA 190 200 210 220 230 240 IVFFGEDLPD SFSETWLNDS EWLREKITTS GKHPQQPLVI VVGTSLAVYP FASLPEEIPR 250 260 270 280 290 300 KVKRVLCNLE TVGDFKANKR PTDLIVHQYS DEFAEQLVEE LGWQEDFEKI LTAQGGMGDN 310 320 330 340 350 SKEQLLEIVH DLENLSLDQS EHESADKKDK KLQRLNGHDS DEDGASNSSS SQKAAKE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability." Brachmann C.B., Sherman J.M., Devine S.E., Cameron E.E., Pillus L., Boeke J.D. Genes Dev. 9:2888-2902(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: S288c / YPH1.
[2]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI." Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W., Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D., Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E., Churcher C.M. , Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H., DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N., Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K., Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M., Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A., Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S., Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D., Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S., Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B., Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A., Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R., Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A., Vo D.H., Hani J. Nature 387:103-105(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[3]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[4]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	"The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases." Landry J., Sutton A., Tafrov S.T., Heller R.C., Stebbins J., Pillus L., Sternglanz R. Proc. Natl. Acad. Sci. U.S.A. 97:5807-5811(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose." Tanner K.G., Landry J., Sternglanz R., Denu J.M. Proc. Natl. Acad. Sci. U.S.A. 97:14178-14182(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[7]	"A cytosolic NAD-dependent deacetylase, Hst2p, can modulate nucleolar and telomeric silencing in yeast." Perrod S., Cockell M.M., Laroche T., Renauld H., Ducrest A.L., Bonnard C., Gasser S.M. EMBO J. 20:197-209(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[9]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[10]	"Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases." Borra M.T., Langer M.R., Slama J.T., Denu J.M. Biochemistry 43:9877-9887(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[11]	"Nuclear export modulates the cytoplasmic Sir2 homologue Hst2." Wilson J.M., Le V.Q., Zimmerman C., Marmorstein R., Pillus L. EMBO Rep. 7:1247-1251(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[12]	"Use of substrate analogs and mutagenesis to study substrate binding and catalysis in the Sir2 family of NAD-dependent protein deacetylases." Khan A.N., Lewis P.N. J. Biol. Chem. 281:11702-11711(2006) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[13]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-340, MASS SPECTROMETRY.
[14]	"Investigation of the catalytic mechanism of Sir2 enzyme with QM/MM approach: SN1 vs SN2?" Liang Z., Shi T., Ouyang S., Li H., Yu K., Zhu W., Luo C., Jiang H. J. Phys. Chem. B 114:11927-11933(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ACTIVE SITE.
[15]	"Structure and autoregulation of the yeast Hst2 homolog of Sir2." Zhao K., Chai X., Clements A., Marmorstein R. Nat. Struct. Biol. 10:864-871(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH PEPTIDE SUBSTRATE; ZINC AND NAD.
[16]	"Structure of the yeast Hst2 protein deacetylase in ternary complex with 2'-O-acetyl ADP ribose and histone peptide." Zhao K., Chai X., Marmorstein R. Structure 11:1403-1411(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 5-293 IN COMPLEX WITH SUBSTRATE ANALOG; PEPTIDE SUBSTRATE AND ZINC, SUBUNIT.
[17]	"Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD(+)-dependent Sir2 histone/protein deacetylases." Zhao K., Harshaw R., Chai X., Marmorstein R. Proc. Natl. Acad. Sci. U.S.A. 101:8563-8568(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-294 IN COMPLEX WITH PEPTIDE SUBSTRATE; ZINC AND NAD.
[18]	"Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes." Sanders B.D., Zhao K., Slama J.T., Marmorstein R. Mol. Cell 25:463-472(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-294 IN COMPLEX WITH PEPTIDE SUBSTRATE; NICOTINAMIDE AND ZINC, MUTAGENESIS OF 117, BIOPHYSICOCHEMICAL PROPERTIES.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U39063 Genomic DNA. Translation: AAA81035.1.
U33335 Genomic DNA. Translation: AAB68090.1.
AY693204 Genomic DNA. Translation: AAT93223.1.
BK006949 Genomic DNA. Translation: DAA11413.1.

PIR

S59678.

RefSeq

NP_015310.1. NM_001183829.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Q14	X-ray	2.50	A	1-357	[»]
1Q17	X-ray	2.70	A/B/C	1-294	[»]
1Q1A	X-ray	1.50	A	5-293	[»]
1SZC	X-ray	1.75	A	1-294	[»]
1SZD	X-ray	1.50	A	1-294	[»]
2OD2	X-ray	2.00	A	1-294	[»]
2OD7	X-ray	2.00	A	1-294	[»]
2OD9	X-ray	2.05	A	1-294	[»]
2QQF	X-ray	2.00	A	1-294	[»]
2QQG	X-ray	2.05	A	1-294	[»]

ProteinModelPortal

P53686.

SMR

P53686. Positions 5-293.

ModBase

Search...

Protein-protein interaction databases

STRING

4932.YPL015C.

Proteomic databases

PaxDb

P53686.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YPL015C; YPL015C; YPL015C.

GeneID

856092.

KEGG

sce:YPL015C.

Organism-specific databases

CYGD

YPL015c.

SGD

S000005936. HST2.

Phylogenomic databases

eggNOG

COG0846.

GeneTree

ENSGT00680000099776.

HOGENOM

HOG000085952.

KO

K11121.

OMA

CKNIVLM.

OrthoDB

EOG4FR425.

Enzyme and pathway databases

SABIO-RK

P53686.

Gene expression databases

Genevestigator

P53686.

GermOnline

YPL015C. Saccharomyces cerevisiae.

Family and domain databases

Gene3D

3.30.1600.10. 2 hits.

InterPro

IPR017328. NAD-dep_deAcase_SIR2_class_I.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]

PANTHER

PTHR11085. PTHR11085. 1 hit.

Pfam

PF02146. SIR2. 1 hit.
[Graphical view]

PIRSF

PIRSF037938. SIR2_euk. 1 hit.

PROSITE

PS50305. SIRTUIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P53686.

ChEMBL

CHEMBL5933.

EvolutionaryTrace

P53686.

NextBio

981122.

Entry information

Entry name

HST2_YEAST

Accession

Primary (citable) accession number: P53686
Secondary accession number(s): D6W3Z7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 119 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program