ID NPD1_ARCFU Reviewed; 245 AA.
AC O28597;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 27-MAR-2024, entry version 149.
DE RecName: Full=NAD-dependent protein deacylase 1 {ECO:0000255|HAMAP-Rule:MF_01121};
DE EC=2.3.1.286 {ECO:0000255|HAMAP-Rule:MF_01121, ECO:0000255|PROSITE-ProRule:PRU00236};
DE AltName: Full=Regulatory protein SIR2 homolog 1 {ECO:0000255|HAMAP-Rule:MF_01121};
DE AltName: Full=SIR2-Af1;
GN Name=cobB1 {ECO:0000255|HAMAP-Rule:MF_01121}; OrderedLocusNames=AF_1676;
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 MUTAGENESIS OF MET-162; GLN-191 AND PRO-216.
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 [4]
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 [5]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH NAD AND ZINC, AND
RP COFACTOR.
RC STRAIN=ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16;
RX PubMed=11336676; DOI=10.1016/s0092-8674(01)00317-8;
RA Min J., Landry J., Sternglanz R., Xu R.-M.;
RT "Crystal structure of a SIR2 homolog-NAD complex.";
RL Cell 105:269-279(2001).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) IN COMPLEX WITH ZINC AND ADP-RIBOSE,
RP COFACTOR, AND MUTAGENESIS OF SER-24; ARG-33; GLU-45; HIS-80; ASP-101;
RP HIS-116 AND PHE-159.
RX PubMed=12091395; DOI=10.1074/jbc.m205460200;
RA Chang J.-H., Kim H.-C., Hwang K.-Y., Lee J.-W., Jackson S.P., Bell S.D.,
RA Cho Y.;
RT "Structural basis for the NAD-dependent deacetylase mechanism of Sir2.";
RL J. Biol. Chem. 277:34489-34498(2002).
CC -!- FUNCTION: NAD-dependent lysine deacetylase and desuccinylase that
CC specifically removes acetyl and succinyl groups on target proteins.
CC Modulates the activities of several proteins which are inactive in
CC their acylated form. Deacetylates the N-terminal lysine residue of
CC Alba, the major archaeal chromatin protein and that, in turn, increases
CC Alba's DNA binding affinity, thereby repressing transcription.
CC {ECO:0000255|HAMAP-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 -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-succinyl-L-lysyl-[protein] + NAD(+) = 2''-O-
CC succinyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:47668, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:11877,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:87830, ChEBI:CHEBI:87832;
CC 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:11336676, ECO:0000269|PubMed:12091395};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01121,
CC ECO:0000269|PubMed:11336676, ECO:0000269|PubMed:12091395};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01121}.
CC -!- DOMAIN: 2 residues (Tyr-64 and Arg-67) present in a large hydrophobic
CC pocket are probably involved in substrate specificity. They are
CC important for desuccinylation activity, but dispensable for
CC deacetylation activity. {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. Af1 cannot
CC deacetylate histones but does deacetylate BSA in a NAD-dependent manner
CC (PubMed:11336676). {ECO:0000305|PubMed:11336676}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01121}.
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DR EMBL; AE000782; AAB89569.1; -; Genomic_DNA.
DR PIR; C69459; C69459.
DR RefSeq; WP_010879172.1; NC_000917.1.
DR PDB; 1ICI; X-ray; 2.10 A; A/B=1-245.
DR PDB; 1M2G; X-ray; 1.70 A; A=1-245.
DR PDB; 1M2H; X-ray; 1.80 A; A=1-245.
DR PDB; 1M2J; X-ray; 1.70 A; A=1-245.
DR PDB; 1M2K; X-ray; 1.47 A; A=1-245.
DR PDB; 1M2N; X-ray; 2.60 A; A/B=1-245.
DR PDB; 4TWI; X-ray; 1.79 A; A=1-245.
DR PDBsum; 1ICI; -.
DR PDBsum; 1M2G; -.
DR PDBsum; 1M2H; -.
DR PDBsum; 1M2J; -.
DR PDBsum; 1M2K; -.
DR PDBsum; 1M2N; -.
DR PDBsum; 4TWI; -.
DR AlphaFoldDB; O28597; -.
DR SMR; O28597; -.
DR STRING; 224325.AF_1676; -.
DR PaxDb; 224325-AF_1676; -.
DR EnsemblBacteria; AAB89569; AAB89569; AF_1676.
DR GeneID; 24795419; -.
DR KEGG; afu:AF_1676; -.
DR eggNOG; arCOG04248; Archaea.
DR HOGENOM; CLU_023643_3_1_2; -.
DR OrthoDB; 728at2157; -.
DR PhylomeDB; O28597; -.
DR BRENDA; 2.3.1.286; 414.
DR BRENDA; 2.3.1.B43; 414.
DR EvolutionaryTrace; O28597; -.
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:UniProtKB-UniRule.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR CDD; cd01412; SIRT5_Af1_CobB; 1.
DR Gene3D; 3.30.1600.10; SIR2/SIRT2 'Small Domain; 1.
DR Gene3D; 3.40.50.1220; TPP-binding domain; 1.
DR HAMAP; MF_01121; Sirtuin_ClassIII; 1.
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; IPR026590; Ssirtuin_cat_dom.
DR NCBIfam; NF040867; prot_deacyl_CobB; 1.
DR PANTHER; PTHR11085:SF12; NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL; 1.
DR PANTHER; PTHR11085; NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL-RELATED; 1.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 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..245
FT /note="NAD-dependent protein deacylase 1"
FT /id="PRO_0000110377"
FT DOMAIN 1..243
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT ACT_SITE 116
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 20..39
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:11336676"
FT BINDING 64
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 67
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 98..101
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:11336676"
FT BINDING 124
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:11336676, ECO:0000269|PubMed:12091395"
FT BINDING 127
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:11336676, ECO:0000269|PubMed:12091395"
FT BINDING 145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:11336676, ECO:0000269|PubMed:12091395"
FT BINDING 148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:11336676, ECO:0000269|PubMed:12091395"
FT BINDING 185..187
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:11336676"
FT BINDING 211..213
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:11336676"
FT BINDING 229
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:11336676"
FT MUTAGEN 24
FT /note="S->A: Reduces activity 6-fold. Reduces affinity for
FT NAD 10-fold."
FT /evidence="ECO:0000269|PubMed:12091395"
FT MUTAGEN 33
FT /note="R->A: Reduces activity by 20%."
FT /evidence="ECO:0000269|PubMed:12091395"
FT MUTAGEN 45
FT /note="E->A: No effect."
FT /evidence="ECO:0000269|PubMed:12091395"
FT MUTAGEN 80
FT /note="H->N: Slightly reduces affinity for NAD."
FT /evidence="ECO:0000269|PubMed:12091395"
FT MUTAGEN 101
FT /note="D->N: Reduces activity 80-fold. Reduces affinity for
FT NAD 10-fold."
FT /evidence="ECO:0000269|PubMed:12091395"
FT MUTAGEN 116
FT /note="H->D,N: Reduces activity 30-fold."
FT /evidence="ECO:0000269|PubMed:12091395"
FT MUTAGEN 159
FT /note="F->A: Reduces activity 20-fold."
FT /evidence="ECO:0000269|PubMed:12091395"
FT MUTAGEN 162
FT /note="M->P: Change in substrate affinity; when associated
FT with Y-191 and M-216."
FT /evidence="ECO:0000269|PubMed:12408821"
FT MUTAGEN 191
FT /note="Q->Y: Change in substrate affinity; when associated
FT with P-162 and M-216."
FT /evidence="ECO:0000269|PubMed:12408821"
FT MUTAGEN 216
FT /note="P->M: Change in substrate affinity; when associated
FT with P-162 and Y-191."
FT /evidence="ECO:0000269|PubMed:12408821"
FT HELIX 3..10
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 13..19
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 21..27
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:1M2N"
FT HELIX 38..41
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 44..47
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 50..55
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 57..73
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 78..88
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 92..97
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 117..128
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 146..156
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 165..177
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 179..185
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 196..202
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 206..210
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 218..220
FT /evidence="ECO:0007829|PDB:1M2K"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:1M2K"
FT HELIX 229..245
FT /evidence="ECO:0007829|PDB:1M2K"
SQ SEQUENCE 245 AA; 27143 MW; 29E365517F480418 CRC64;
MDEKLLKTIA ESKYLVALTG AGVSAESGIP TFRGKDGLWN RYRPEELANP QAFAKDPEKV
WKWYAWRMEK VFNAQPNKAH QAFAELERLG VLKCLITQNV DDLHERAGSR NVIHLHGSLR
VVRCTSCNNS FEVESAPKIP PLPKCDKCGS LLRPGVVWFG EMLPPDVLDR AMREVERADV
IIVAGTSAVV QPAASLPLIV KQRGGAIIEI NPDETPLTPI ADYSLRGKAG EVMDELVRHV
RKALS
//
