NPD2_ARCFU
ID NPD2_ARCFU Reviewed; 253 AA.
AC O30124;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=NAD-dependent protein deacylase 2 {ECO:0000255|HAMAP-Rule:MF_01121};
DE EC=2.3.1.286 {ECO:0000255|HAMAP-Rule:MF_01121};
DE AltName: Full=Regulatory protein SIR2 homolog 2 {ECO:0000255|HAMAP-Rule:MF_01121};
DE AltName: Full=SIR2-Af2;
GN Name=cobB2 {ECO:0000255|HAMAP-Rule:MF_01121}; Synonyms=Sir2Af2;
GN OrderedLocusNames=AF_0112;
OS Archaeoglobus fulgidus (strain ATCC 49558 / DSM 4304 / JCM 9628 / NBRC
OS 100126 / VC-16).
OC Archaea; Euryarchaeota; Archaeoglobi; Archaeoglobales; Archaeoglobaceae;
OC Archaeoglobus.
OX NCBI_TaxID=224325;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16;
RX PubMed=9389475; DOI=10.1038/37052;
RA Klenk H.-P., Clayton R.A., Tomb J.-F., White O., Nelson K.E., Ketchum K.A.,
RA Dodson R.J., Gwinn M.L., Hickey E.K., Peterson J.D., Richardson D.L.,
RA Kerlavage A.R., Graham D.E., Kyrpides N.C., Fleischmann R.D.,
RA Quackenbush J., Lee N.H., Sutton G.G., Gill S.R., Kirkness E.F.,
RA Dougherty B.A., McKenney K., Adams M.D., Loftus B.J., Peterson S.N.,
RA Reich C.I., McNeil L.K., Badger J.H., Glodek A., Zhou L., Overbeek R.,
RA Gocayne J.D., Weidman J.F., McDonald L.A., Utterback T.R., Cotton M.D.,
RA Spriggs T., Artiach P., Kaine B.P., Sykes S.M., Sadow P.W., D'Andrea K.P.,
RA Bowman C., Fujii C., Garland S.A., Mason T.M., Olsen G.J., Fraser C.M.,
RA Smith H.O., Woese C.R., Venter J.C.;
RT "The complete genome sequence of the hyperthermophilic, sulphate-reducing
RT archaeon Archaeoglobus fulgidus.";
RL Nature 390:364-370(1997).
RN [2]
RP FUNCTION AS A NAD-DEPENDENT DEACETYLASE.
RX PubMed=10841563; DOI=10.1073/pnas.97.12.6658;
RA Smith J.S., Brachmann C.B., Celic I., Kenna M.A., Muhammad S., Starai V.J.,
RA Avalos J.L., Escalante-Semerena J.C., Grubmeyer C., Wolberger C.,
RA Boeke J.D.;
RT "A phylogenetically conserved NAD+-dependent protein deacetylase activity
RT in the Sir2 protein family.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6658-6663(2000).
RN [3]
RP REVIEW.
RX PubMed=11336664; DOI=10.1016/s0092-8674(01)00305-1;
RA Dutnall R.N., Pillus L.;
RT "Deciphering NAD-dependent deacetylases.";
RL Cell 105:161-164(2001).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF COMPLEX WITH AN ACETYLATED P53
RP PEPTIDE AND ZINC, AND COFACTOR.
RX PubMed=12408821; DOI=10.1016/s1097-2765(02)00628-7;
RA Avalos J.L., Celic I., Muhammad S., Cosgrove M.S., Boeke J.D.,
RA Wolberger C.;
RT "Structure of a Sir2 enzyme bound to an acetylated p53 peptide.";
RL Mol. Cell 10:523-535(2002).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH ZINC AND NAD, AND
RP COFACTOR.
RX PubMed=15023335; DOI=10.1016/s1097-2765(04)00082-6;
RA Avalos J.L., Boeke J.D., Wolberger C.;
RT "Structural basis for the mechanism and regulation of Sir2 enzymes.";
RL Mol. Cell 13:639-648(2004).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH NAD; ZINC AND
RP NICOTINAMIDE, AND COFACTOR.
RX PubMed=15780941; DOI=10.1016/j.molcel.2005.02.022;
RA Avalos J.L., Bever K.M., Wolberger C.;
RT "Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+)
RT cosubstrate specificity of a Sir2 enzyme.";
RL Mol. Cell 17:855-868(2005).
CC -!- FUNCTION: NAD-dependent protein deacetylase which modulates the
CC activities of several proteins which are inactive in their acetylated
CC form. Deacetylates the N-terminal lysine residue of Alba, the major
CC archaeal chromatin protein and that, in turn, increases Alba's DNA
CC binding affinity, thereby repressing transcription. {ECO:0000255|HAMAP-
CC Rule:MF_01121, ECO:0000269|PubMed:10841563}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
CC ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
CC EC=2.3.1.286; Evidence={ECO:0000255|HAMAP-Rule:MF_01121};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01121,
CC ECO:0000269|PubMed:12408821, ECO:0000269|PubMed:15023335,
CC ECO:0000269|PubMed:15780941};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01121,
CC ECO:0000269|PubMed:12408821, ECO:0000269|PubMed:15023335,
CC ECO:0000269|PubMed:15780941};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01121}.
CC -!- MISCELLANEOUS: The two SIR2 homologs in this organism, Af1 and Af2,
CC display different substrate specificities in vitro. Af2 can deacetylate
CC histones and peptides corresponding to the C-terminal part of p53 in a
CC NAD-dependent manner (PubMed:12408821). {ECO:0000305|PubMed:12408821}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01121}.
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DR EMBL; AE000782; AAB91115.1; -; Genomic_DNA.
DR PIR; H69263; H69263.
DR RefSeq; WP_010877626.1; NC_000917.1.
DR PDB; 1MA3; X-ray; 2.00 A; A=1-253.
DR PDB; 1S7G; X-ray; 2.30 A; A/B/C/D/E=1-253.
DR PDB; 1YC2; X-ray; 2.40 A; A/B/C/D/E=1-253.
DR PDB; 4TWJ; X-ray; 1.65 A; A=1-253.
DR PDBsum; 1MA3; -.
DR PDBsum; 1S7G; -.
DR PDBsum; 1YC2; -.
DR PDBsum; 4TWJ; -.
DR AlphaFoldDB; O30124; -.
DR SMR; O30124; -.
DR STRING; 224325.AF_0112; -.
DR PRIDE; O30124; -.
DR EnsemblBacteria; AAB91115; AAB91115; AF_0112.
DR GeneID; 24793666; -.
DR KEGG; afu:AF_0112; -.
DR eggNOG; arCOG04248; Archaea.
DR HOGENOM; CLU_023643_3_1_2; -.
DR OMA; ERDCHGL; -.
DR OrthoDB; 82426at2157; -.
DR PhylomeDB; O30124; -.
DR BRENDA; 2.3.1.B41; 414.
DR EvolutionaryTrace; O30124; -.
DR Proteomes; UP000002199; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0070403; F:NAD+ binding; IEA:UniProtKB-UniRule.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0036054; F:protein-malonyllysine demalonylase activity; IEA:InterPro.
DR GO; GO:0036055; F:protein-succinyllysine desuccinylase activity; IEA:InterPro.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006476; P:protein deacetylation; IEA:UniProtKB-UniRule.
DR Gene3D; 3.30.1600.10; -; 1.
DR HAMAP; MF_01121; Sirtuin_ClassIII; 1.
DR HAMAP; MF_01968; Sirtuin_ClassU; 1.
DR IDEAL; IID90001; -.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR027546; Sirtuin_class_III.
DR InterPro; IPR028628; Sirtuin_class_U.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Metal-binding; NAD; Reference proteome;
KW Transcription; Transcription regulation; Transferase; Zinc.
FT CHAIN 1..253
FT /note="NAD-dependent protein deacylase 2"
FT /id="PRO_0000110378"
FT DOMAIN 6..251
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT ACT_SITE 118
FT /note="Proton acceptor"
FT BINDING 23..42
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15023335, ECO:0000269|PubMed:15780941"
FT BINDING 100..103
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15023335, ECO:0000269|PubMed:15780941"
FT BINDING 126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15023335, ECO:0000269|PubMed:15780941"
FT BINDING 129
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15023335, ECO:0000269|PubMed:15780941"
FT BINDING 150
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15023335, ECO:0000269|PubMed:15780941"
FT BINDING 153
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15023335, ECO:0000269|PubMed:15780941"
FT BINDING 191..193
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15023335, ECO:0000269|PubMed:15780941"
FT BINDING 217..219
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15023335, ECO:0000269|PubMed:15780941"
FT BINDING 235
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15023335, ECO:0000269|PubMed:15780941"
FT HELIX 2..14
FT /evidence="ECO:0007829|PDB:4TWJ"
FT STRAND 16..22
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 24..26
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:1S7G"
FT HELIX 48..51
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 53..58
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 60..73
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 80..90
FT /evidence="ECO:0007829|PDB:4TWJ"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 105..108
FT /evidence="ECO:0007829|PDB:4TWJ"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:4TWJ"
FT STRAND 119..126
FT /evidence="ECO:0007829|PDB:4TWJ"
FT TURN 127..129
FT /evidence="ECO:0007829|PDB:4TWJ"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 139..143
FT /evidence="ECO:0007829|PDB:4TWJ"
FT TURN 151..153
FT /evidence="ECO:0007829|PDB:4TWJ"
FT STRAND 158..162
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 171..182
FT /evidence="ECO:0007829|PDB:4TWJ"
FT STRAND 185..191
FT /evidence="ECO:0007829|PDB:4TWJ"
FT TURN 197..200
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 201..208
FT /evidence="ECO:0007829|PDB:4TWJ"
FT STRAND 212..219
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:4TWJ"
FT STRAND 228..233
FT /evidence="ECO:0007829|PDB:4TWJ"
FT HELIX 235..249
FT /evidence="ECO:0007829|PDB:4TWJ"
SQ SEQUENCE 253 AA; 28495 MW; 71A243C9012CBBFE CRC64;
MEDEIRKAAE ILAKSKHAVV FTGAGISAES GIPTFRGEDG LWRKYDPEEV ASISGFKRNP
RAFWEFSMEM KDKLFAEPNP AHYAIAELER MGIVKAVITQ NIDMLHQRAG SRRVLELHGS
MDKLDCLDCH ETYDWSEFVE DFNKGEIPRC RKCGSYYVKP RVVLFGEPLP QRTLFEAIEE
AKHCDAFMVV GSSLVVYPAA ELPYIAKKAG AKMIIVNAEP TMADPIFDVK IIGKAGEVLP
KIVEEVKRLR SEK
