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P53686 (HST2_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length357 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.17

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.19

KM=0.92 µM for acetylated poly-L-lysine

KM=0.5 µM for a synthetic histone H3K14 acetyllysine peptide

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.15
Chain2 – 357356NAD-dependent protein deacetylase HST2
PRO_0000110282

Regions

Domain13 – 286274Deacetylase sirtuin-type
Nucleotide binding32 – 5221NAD
Nucleotide binding115 – 1184NAD
Nucleotide binding223 – 2253NAD
Nucleotide binding248 – 2503NAD

Sites

Active site1351Proton acceptor Ref.14
Metal binding1431Zinc
Metal binding1461Zinc
Metal binding1701Zinc
Metal binding1731Zinc
Binding site2701NAD; via amide nitrogen

Amino acid modifications

Modified residue21N-acetylserine Ref.15
Modified residue3401Phosphoserine Ref.13

Experimental info

Mutagenesis1171I → A, D, H, W or Y: Nearly or completely catalytically inactive. Ref.19
Mutagenesis1171I → F or V: Near wild-type activity for deacetylation. Increases slightly the KM for NAD(+) to 25 uM. Ref.19

Secondary structure

............................................................... 357
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P53686 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: ED281E5B8241A4D0

FASTA35739,979
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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 204508 / S288c.
[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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[16]"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.
[17]"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.
[18]"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.
[19]"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.
PIRS59678.
RefSeqNP_015310.1. NM_001183829.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Q14X-ray2.50A1-357[»]
1Q17X-ray2.70A/B/C1-294[»]
1Q1AX-ray1.50A5-293[»]
1SZCX-ray1.75A1-294[»]
1SZDX-ray1.50A1-294[»]
2OD2X-ray2.00A1-294[»]
2OD7X-ray2.00A1-294[»]
2OD9X-ray2.05A1-294[»]
2QQFX-ray2.00A1-294[»]
2QQGX-ray2.05A1-294[»]
ProteinModelPortalP53686.
SMRP53686. Positions 5-293.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid36162. 36 interactions.
IntActP53686. 2 interactions.
MINTMINT-4504340.
STRING4932.YPL015C.

Chemistry

BindingDBP53686.
ChEMBLCHEMBL5933.

Proteomic databases

PaxDbP53686.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblFungiYPL015C; YPL015C; YPL015C.
GeneID856092.
KEGGsce:YPL015C.

Organism-specific databases

CYGDYPL015c.
SGDS000005936. HST2.

Phylogenomic databases

eggNOGCOG0846.
GeneTreeENSGT00740000115546.
HOGENOMHOG000085952.
KOK11121.
OMAFRPTIAH.
OrthoDBEOG7MWH64.

Enzyme and pathway databases

BioCycYEAST:G3O-33934-MONOMER.
SABIO-RKP53686.

Gene expression databases

GenevestigatorP53686.

Family and domain databases

Gene3D3.30.1600.10. 2 hits.
InterProIPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR017328. Sirtuin_class_I.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERPTHR11085. PTHR11085. 1 hit.
PfamPF02146. SIR2. 1 hit.
[Graphical view]
PIRSFPIRSF037938. SIR2_euk. 1 hit.
PROSITEPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP53686.
NextBio981122.
PROP53686.

Entry information

Entry nameHST2_YEAST
AccessionPrimary (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: April 16, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome XVI

Yeast (Saccharomyces cerevisiae) chromosome XVI: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references