O28597 (NPD1_ARCFU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NAD-dependent protein deacylase 1
EC=3.5.1.-

Alternative name(s):
Regulatory protein SIR2 homolog 1
SIR2-Af1

Gene names

Name:	cobB1
Ordered Locus Names:	AF_1676

Organism

Archaeoglobus fulgidus (strain ATCC 49558 / VC-16 / DSM 4304 / JCM 9628 / NBRC 100126) [Reference proteome] [HAMAP]

Taxonomic identifier

224325 [NCBI]

Taxonomic lineage

cellular organisms › Archaea › Euryarchaeota › Archaeoglobi › Archaeoglobales › Archaeoglobaceae › Archaeoglobus › Archaeoglobus fulgidus

Protein attributes

Sequence length	245 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Deacetylates the N-terminal lysine residue of Alba, the major archaeal chromatin protein and that, in turn, increases Alba's DNA binding affinity, thereby repressing transcription. May also have NAD-dependent lysine demalonylase and desuccinylase activity By similarity. HAMAP-Rule MF_01121
Catalytic activity	NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein. HAMAP-Rule MF_01121
Cofactor	Binds 1 zinc ion per subunit.
Subcellular location	Cytoplasm By similarity HAMAP-Rule MF_01121.
Domain	In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-64 and Arg-67) that bind to malonylated and succinylated substrates and define the specificity By similarity. HAMAP-Rule MF_01121
Miscellaneous	The two SIR2 homologs in this organism, Af1 and Af2, display different substrate specificities in vitro. Af1 cannot deacetylate histones but does deacetylate BSA in a NAD-dependent manner. HAMAP-Rule MF_01121
Sequence similarities	Belongs to the sirtuin family. Class III subfamily. Contains 1 deacetylase sirtuin-type domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm
Ligand	Metal-binding NAD Zinc
Molecular function	Hydrolase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	peptidyl-lysine demalonylation Inferred from electronic annotation. Source: GOC peptidyl-lysine desuccinylation Inferred from electronic annotation. Source: GOC regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	NAD+ binding Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein-malonyllysine demalonylase activity Inferred from electronic annotation. Source: InterPro protein-succinyllysine desuccinylase activity 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 – 245

245

NAD-dependent protein deacylase 1 HAMAP-Rule MF_01121

PRO_0000110377

Regions

Domain

3 – 245

243

Deacetylase sirtuin-type

Nucleotide binding

20 – 39

20

NAD HAMAP-Rule MF_01121

Nucleotide binding

98 – 101

4

NAD HAMAP-Rule MF_01121

Nucleotide binding

185 – 187

3

NAD HAMAP-Rule MF_01121

Nucleotide binding

211 – 213

3

NAD HAMAP-Rule MF_01121

Sites

Active site

116

1

Proton acceptor

Metal binding

124

1

Zinc

Metal binding

127

1

Zinc

Metal binding

145

1

Zinc

Metal binding

148

1

Zinc

Binding site

64

1

Substrate By similarity

Binding site

67

1

Substrate By similarity

Binding site

229

1

NAD; via amide nitrogen

Experimental info

Mutagenesis

24

1

S → A: Reduces activity 6-fold. Reduces affinity for NAD 10-fold. Ref.6

Mutagenesis

33

1

R → A: Reduces activity by 20%. Ref.6

Mutagenesis

45

1

E → A: No effect. Ref.6

Mutagenesis

80

1

H → N: Slightly reduces affinity for NAD. Ref.6

Mutagenesis

101

1

D → N: Reduces activity 80-fold. Reduces affinity for NAD 10-fold. Ref.6

Mutagenesis

116

1

H → D or N: Reduces activity 30-fold. Ref.6

Mutagenesis

159

1

F → A: Reduces activity 20-fold. Ref.6

Mutagenesis

162

1

M → P: Change in substrate affinity; when associated with Y-191 and M-216. Ref.3

Mutagenesis

191

1

Q → Y: Change in substrate affinity; when associated with P-162 and M-216. Ref.3

Mutagenesis

216

1

P → M: Change in substrate affinity; when associated with P-162 and Y-191. Ref.3

Secondary structure

1

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245

Helix Strand Turn

Details...

Helix

3 – 10

8

Beta strand

13 – 19

7

Helix

21 – 27

7

Beta strand

32 – 34

3

Helix

35 – 37

3

Helix

38 – 41

4

Helix

44 – 47

4

Helix

50 – 55

6

Helix

57 – 73

17

Helix

78 – 88

11

Beta strand

92 – 97

6

Helix

103 – 106

4

Beta strand

111 – 114

4

Beta strand

117 – 128

12

Beta strand

130 – 132

3

Beta strand

139 – 141

3

Beta strand

146 – 156

11

Helix

165 – 177

13

Beta strand

179 – 185

7

Helix

193 – 195

3

Helix

196 – 202

7

Beta strand

206 – 210

5

Helix

218 – 220

3

Beta strand

222 – 225

4

Helix

229 – 245

17

Sequences

	Sequence		Length	Mass (Da)
	O28597 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 29E365517F480418	FASTA	245	27,143
	10 20 30 40 50 60 MDEKLLKTIA ESKYLVALTG AGVSAESGIP TFRGKDGLWN RYRPEELANP QAFAKDPEKV 70 80 90 100 110 120 WKWYAWRMEK VFNAQPNKAH QAFAELERLG VLKCLITQNV DDLHERAGSR NVIHLHGSLR 130 140 150 160 170 180 VVRCTSCNNS FEVESAPKIP PLPKCDKCGS LLRPGVVWFG EMLPPDVLDR AMREVERADV 190 200 210 220 230 240 IIVAGTSAVV QPAASLPLIV KQRGGAIIEI NPDETPLTPI ADYSLRGKAG EVMDELVRHV RKALS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The complete genome sequence of the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus." Klenk H.-P., Clayton R.A., Tomb J.-F., White O., Nelson K.E., Ketchum K.A., Dodson R.J., Gwinn M.L., Hickey E.K., Peterson J.D., Richardson D.L., Kerlavage A.R., Graham D.E., Kyrpides N.C., Fleischmann R.D., Quackenbush J., Lee N.H., Sutton G.G. , Gill S.R., Kirkness E.F., Dougherty B.A., McKenney K., Adams M.D., Loftus B.J., Peterson S.N., Reich C.I., McNeil L.K., Badger J.H., Glodek A., Zhou L., Overbeek R., Gocayne J.D., Weidman J.F., McDonald L.A., Utterback T.R., Cotton M.D., Spriggs T., Artiach P., Kaine B.P., Sykes S.M., Sadow P.W., D'Andrea K.P., Bowman C., Fujii C., Garland S.A., Mason T.M., Olsen G.J., Fraser C.M., Smith H.O., Woese C.R., Venter J.C. Nature 390:364-370(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 49558 / VC-16 / DSM 4304 / JCM 9628 / NBRC 100126.
[2]	"A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family." Smith J.S., Brachmann C.B., Celic I., Kenna M.A., Muhammad S., Starai V.J., Avalos J.L., Escalante-Semerena J.C., Grubmeyer C., Wolberger C., Boeke J.D. Proc. Natl. Acad. Sci. U.S.A. 97:6658-6663(2000) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[3]	"Structure of a Sir2 enzyme bound to an acetylated p53 peptide." Avalos J.L., Celic I., Muhammad S., Cosgrove M.S., Boeke J.D., Wolberger C. Mol. Cell 10:523-535(2002) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF MET-162; GLN-191 AND PRO-216.
[4]	"Deciphering NAD-dependent deacetylases." Dutnall R.N., Pillus L. Cell 105:161-164(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[5]	"Crystal structure of a SIR2 homolog-NAD complex." Min J., Landry J., Sternglanz R., Xu R.-M. Cell 105:269-279(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS). Strain: ATCC 49558 / VC-16 / DSM 4304 / JCM 9628 / NBRC 100126.
[6]	"Structural basis for the NAD-dependent deacetylase mechanism of Sir2." Chang J.-H., Kim H.-C., Hwang K.-Y., Lee J.-W., Jackson S.P., Bell S.D., Cho Y. J. Biol. Chem. 277:34489-34498(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) IN COMPLEX WITH NAD AND WITH ADP-RIBOSE, MUTAGENESIS OF SER-24; ARG-33; GLU-45; HIS-80; ASP-101; HIS-116 AND PHE-159.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AE000782 Genomic DNA. Translation: AAB89569.1.

PIR

C69459.

RefSeq

NP_070504.1. NC_000917.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ICI	X-ray	2.10	A/B	1-245	[»]
1M2G	X-ray	1.70	A	1-245	[»]
1M2H	X-ray	1.80	A	1-245	[»]
1M2J	X-ray	1.70	A	1-245	[»]
1M2K	X-ray	1.47	A	1-245	[»]
1M2N	X-ray	2.60	A/B	1-245	[»]

ProteinModelPortal

O28597.

SMR

O28597. Positions 1-245.

ModBase

Search...

Protein-protein interaction databases

STRING

224325.AF1676.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAB89569; AAB89569; AF_1676.

GeneID

1484899.

KEGG

afu:AF1676.

Phylogenomic databases

eggNOG

COG0846.

KO

K12410.

OMA

VLHMHGE.

ProtClustDB

PRK00481.

Enzyme and pathway databases

BioCyc

AFUL224325:GJBC-1710-MONOMER.

Family and domain databases

Gene3D

3.30.1600.10. 2 hits.

HAMAP

MF_01121. Sirtuin_ClassIII.

InterPro

IPR003000. Sirtuin.
IPR026591. Sirtuin_cat_small_dom.
IPR027546. Sirtuin_ClassIII.
IPR026590. Ssirtuin_cat_dom.
[Graphical view]

PANTHER

PTHR11085. PTHR11085. 1 hit.

Pfam

PF02146. SIR2. 1 hit.
[Graphical view]

PROSITE

PS50305. SIRTUIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O28597.

Entry information

Entry name

NPD1_ARCFU

Accession

Primary (citable) accession number: O28597

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2003
Last sequence update:	January 1, 1998
Last modified:	May 29, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program