Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9WYW0 (NPD_THEMA) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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

EC=3.5.1.-
Alternative name(s):
Regulatory protein SIR2 homolog
Short name=Sir2Tm
Gene names
Name:cobB
Synonyms:sir2
Ordered Locus Names:TM_0490
OrganismThermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099) [Reference proteome] [HAMAP]
Taxonomic identifier243274 [NCBI]
Taxonomic lineageBacteriaThermotogaeThermotogalesThermotogaceaeThermotoga

Protein attributes

Sequence length246 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

NAD-dependent protein deacetylase which modulates the activities of several enzymes which are inactive in their acetylated form. Has also depropionylation activity in vitro. Also able to ADP-ribosylate peptide substrates with Arg or Lys in the +2 position. The role of this function in vivo is not clear. Ref.2 Ref.5 Ref.8

Catalytic activity

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. Ref.5

Cofactor

Binds 1 zinc ion per subunit. Ref.3 Ref.4 Ref.5

Enzyme regulation

Non-competitively inhibited by nicotinamide but not by nicotinic acid. Ref.3

Subcellular location

Cytoplasm By similarity HAMAP-Rule MF_01968.

Sequence similarities

Belongs to the sirtuin family. Class U subfamily.

Contains 1 deacetylase sirtuin-type domain.

Ontologies

Keywords
   Cellular componentCytoplasm
   LigandMetal-binding
NAD
Zinc
   Molecular functionHydrolase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionNAD+ binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

NAD-dependent protein deacetylase activity

Inferred from electronic annotation. Source: UniProtKB-HAMAP

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 246246NAD-dependent protein deacetylase HAMAP-Rule MF_01968
PRO_0000110362

Regions

Domain4 – 246243Deacetylase sirtuin-type
Nucleotide binding21 – 4020NAD HAMAP-Rule MF_01968
Nucleotide binding98 – 1014NAD HAMAP-Rule MF_01968
Nucleotide binding188 – 1903NAD HAMAP-Rule MF_01968
Nucleotide binding214 – 2163NAD HAMAP-Rule MF_01968
Nucleotide binding231 – 2322NAD HAMAP-Rule MF_01968

Sites

Active site1161Proton acceptor Probable
Metal binding1241Zinc
Metal binding1271Zinc
Metal binding1481Zinc
Metal binding1511Zinc

Experimental info

Mutagenesis331F → A: Reduces kcat for NAD(+), greatly increases sensitivity to nicotinamide inhibition. Ref.6
Mutagenesis1011D → N: Alters cosubstrate specificity, decreases Km for NAD(+), enzyme unable to discriminate between NAD(+) and nicotinic acid adenine dinucleotide (NAAD). Ref.3
Mutagenesis1161H → A: 2-fold decrease in turnover and peptide affinity. Ref.5
Mutagenesis1161H → Y: 10-fold decrease in turnover and peptide affinity. Ref.5
Mutagenesis1651N → D: Increased affinity for substrate peptides with a lysine or arginine at position -1. Ref.4

Secondary structure

........................................................ 246
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9WYW0 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 6BD2EF1B751C190D

FASTA24627,538
        10         20         30         40         50         60 
MKMKEFLDLL NESRLTVTLT GAGISTPSGI PDFRGPNGIY KKYSQNVFDI DFFYSHPEEF 

        70         80         90        100        110        120 
YRFAKEGIFP MLQAKPNLAH VLLAKLEEKG LIEAVITQNI DRLHQRAGSK KVIELHGNVE 

       130        140        150        160        170        180 
EYYCVRCEKK YTVEDVIKKL ESSDVPLCDD CNSLIRPNIV FFGENLPQDA LREAIGLSSR 

       190        200        210        220        230        240 
ASLMIVLGSS LVVYPAAELP LITVRSGGKL VIVNLGETPF DDIATLKYNM DVVEFARRVM 


EEGGIS 

« Hide

References

« Hide 'large scale' references
[1]"Evidence for lateral gene transfer between Archaea and Bacteria from genome sequence of Thermotoga maritima."
Nelson K.E., Clayton R.A., Gill S.R., Gwinn M.L., Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Nelson W.C., Ketchum K.A., McDonald L.A., Utterback T.R., Malek J.A., Linher K.D., Garrett M.M., Stewart A.M., Cotton M.D., Pratt M.S. expand/collapse author list , Phillips C.A., Richardson D.L., Heidelberg J.F., Sutton G.G., Fleischmann R.D., Eisen J.A., White O., Salzberg S.L., Smith H.O., Venter J.C., Fraser C.M.
Nature 399:323-329(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 43589 / MSB8 / DSM 3109 / JCM 10099.
[2]"N-lysine propionylation controls the activity of propionyl-CoA synthetase."
Garrity J., Gardner J.G., Hawse W., Wolberger C., Escalante-Semerena J.C.
J. Biol. Chem. 282:30239-30245(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[3]"Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme."
Avalos J.L., Bever K.M., Wolberger C.
Mol. Cell 17:855-868(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH NICOTINAMIDE, ENZYME REGULATION, COFACTOR, MUTAGENESIS OF ASP-101.
[4]"The structural basis of sirtuin substrate affinity."
Cosgrove M.S., Bever K., Avalos J.L., Muhammad S., Zhang X., Wolberger C.
Biochemistry 45:7511-7521(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) IN COMPLEX WITH PEPTIDE SUBSTRATES, COFACTOR, MUTAGENESIS OF ASN-165.
[5]"Insights into the sirtuin mechanism from ternary complexes containing NAD+ and acetylated peptide."
Hoff K.G., Avalos J.L., Sens K., Wolberger C.
Structure 14:1231-1240(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN TERNARY COMPLEX WITH NAD AND PEPTIDE SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF HIS-116.
[6]"Structural insights into intermediate steps in the Sir2 deacetylation reaction."
Hawse W.F., Hoff K.G., Fatkins D.G., Daines A., Zubkova O.V., Schramm V.L., Zheng W., Wolberger C.
Structure 16:1368-1377(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH ANALOGS, MUTAGENESIS OF PHE-33.
[7]"Structure of Sir2Tm bound to a propionylated peptide."
Bheda P., Wang J.T., Escalante-Semerena J.C., Wolberger C.
Protein Sci. 20:131-139(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[8]"Structure-based mechanism of ADP-ribosylation by sirtuins."
Hawse W.F., Wolberger C.
J. Biol. Chem. 284:33654-33661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEX WITH PEPTIDE SUBSTRATES, FUNCTION, CHARACTERIZATION OF ADP-RIBOSYLATION ACTIVITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AE000512 Genomic DNA. Translation: AAD35575.1.
PIRA72370.
RefSeqNP_228300.1. NC_000853.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1YC5X-ray1.40A1-246[»]
2H2DX-ray1.70A1-246[»]
2H2FX-ray2.20A1-246[»]
2H2GX-ray1.63A1-246[»]
2H2HX-ray2.20A1-246[»]
2H2IX-ray1.80A1-246[»]
2H4FX-ray2.00A1-246[»]
2H4HX-ray1.99A1-246[»]
2H4JX-ray2.10A1-246[»]
2H59X-ray1.90A/B1-246[»]
3D4BX-ray1.90A1-246[»]
3D81X-ray2.50A1-246[»]
3JR3X-ray1.50A1-246[»]
3PDHX-ray1.80A1-246[»]
4BUZX-ray1.90A1-246[»]
4BV2X-ray3.30A/B1-246[»]
ProteinModelPortalQ9WYW0.
SMRQ9WYW0. Positions 1-244.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-29141N.
STRING243274.TM0490.

Protocols and materials databases

DNASU897531.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAD35575; AAD35575; TM_0490.
GeneID897531.
KEGGtma:TM0490.
PATRIC23935885. VBITheMar51294_0497.

Phylogenomic databases

eggNOGCOG0846.
KOK12410.
OMARFYCINC.
OrthoDBEOG6VQPX1.

Enzyme and pathway databases

BioCycTMAR243274:GC6P-514-MONOMER.

Family and domain databases

Gene3D3.30.1600.10. 2 hits.
3.40.50.1220. 3 hits.
HAMAPMF_01968. Sirtuin_ClassU.
InterProIPR029035. DHS-like_NAD/FAD-binding_dom.
IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR028628. Sirtuin_class_U.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]
PANTHERPTHR11085. PTHR11085. 1 hit.
PfamPF02146. SIR2. 1 hit.
[Graphical view]
SUPFAMSSF52467. SSF52467. 1 hit.
PROSITEPS50305. SIRTUIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9WYW0.

Entry information

Entry nameNPD_THEMA
AccessionPrimary (citable) accession number: Q9WYW0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: November 1, 1999
Last modified: June 11, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references