NPD_THEMA
ID NPD_THEMA Reviewed; 246 AA.
AC Q9WYW0;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=NAD-dependent protein deacetylase {ECO:0000255|HAMAP-Rule:MF_01968};
DE EC=2.3.1.286 {ECO:0000255|HAMAP-Rule:MF_01968};
DE AltName: Full=Regulatory protein SIR2 homolog {ECO:0000255|HAMAP-Rule:MF_01968};
DE Short=Sir2Tm;
GN Name=cobB {ECO:0000255|HAMAP-Rule:MF_01968}; Synonyms=sir2;
GN OrderedLocusNames=TM_0490;
OS Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826
OS / MSB8).
OC Bacteria; Thermotogae; Thermotogales; Thermotogaceae; Thermotoga.
OX NCBI_TaxID=243274;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX PubMed=10360571; DOI=10.1038/20601;
RA Nelson K.E., Clayton R.A., Gill S.R., Gwinn M.L., Dodson R.J., Haft D.H.,
RA Hickey E.K., Peterson J.D., Nelson W.C., Ketchum K.A., McDonald L.A.,
RA Utterback T.R., Malek J.A., Linher K.D., Garrett M.M., Stewart A.M.,
RA Cotton M.D., Pratt M.S., Phillips C.A., Richardson D.L., Heidelberg J.F.,
RA Sutton G.G., Fleischmann R.D., Eisen J.A., White O., Salzberg S.L.,
RA Smith H.O., Venter J.C., Fraser C.M.;
RT "Evidence for lateral gene transfer between Archaea and Bacteria from
RT genome sequence of Thermotoga maritima.";
RL Nature 399:323-329(1999).
RN [2]
RP FUNCTION.
RX PubMed=17684016; DOI=10.1074/jbc.m704409200;
RA Garrity J., Gardner J.G., Hawse W., Wolberger C., Escalante-Semerena J.C.;
RT "N-lysine propionylation controls the activity of propionyl-CoA
RT synthetase.";
RL J. Biol. Chem. 282:30239-30245(2007).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) IN COMPLEX WITH NICOTINAMIDE,
RP ACTIVITY REGULATION, COFACTOR, AND MUTAGENESIS OF ASP-101.
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).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) IN COMPLEX WITH PEPTIDE SUBSTRATES,
RP COFACTOR, AND MUTAGENESIS OF ASN-165.
RX PubMed=16768447; DOI=10.1021/bi0526332;
RA Cosgrove M.S., Bever K., Avalos J.L., Muhammad S., Zhang X., Wolberger C.;
RT "The structural basis of sirtuin substrate affinity.";
RL Biochemistry 45:7511-7521(2006).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN TERNARY COMPLEX WITH NAD AND
RP PEPTIDE SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS
RP OF HIS-116.
RX PubMed=16905097; DOI=10.1016/j.str.2006.06.006;
RA Hoff K.G., Avalos J.L., Sens K., Wolberger C.;
RT "Insights into the sirtuin mechanism from ternary complexes containing NAD+
RT and acetylated peptide.";
RL Structure 14:1231-1240(2006).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH ANALOGS, AND
RP MUTAGENESIS OF PHE-33.
RX PubMed=18786399; DOI=10.1016/j.str.2008.05.015;
RA Hawse W.F., Hoff K.G., Fatkins D.G., Daines A., Zubkova O.V., Schramm V.L.,
RA Zheng W., Wolberger C.;
RT "Structural insights into intermediate steps in the Sir2 deacetylation
RT reaction.";
RL Structure 16:1368-1377(2008).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
RX PubMed=21080423; DOI=10.1002/pro.544;
RA Bheda P., Wang J.T., Escalante-Semerena J.C., Wolberger C.;
RT "Structure of Sir2Tm bound to a propionylated peptide.";
RL Protein Sci. 20:131-139(2011).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEX WITH PEPTIDE SUBSTRATES,
RP FUNCTION, AND CHARACTERIZATION OF ADP-RIBOSYLATION ACTIVITY.
RX PubMed=19801667; DOI=10.1074/jbc.m109.024521;
RA Hawse W.F., Wolberger C.;
RT "Structure-based mechanism of ADP-ribosylation by sirtuins.";
RL J. Biol. Chem. 284:33654-33661(2009).
CC -!- FUNCTION: NAD-dependent protein deacetylase which modulates the
CC activities of several enzymes which are inactive in their acetylated
CC form. Has also depropionylation activity in vitro. Also able to ADP-
CC ribosylate peptide substrates with Arg or Lys in the +2 position. The
CC role of this function in vivo is not clear. {ECO:0000255|HAMAP-
CC Rule:MF_01968, ECO:0000269|PubMed:16905097,
CC ECO:0000269|PubMed:17684016, ECO:0000269|PubMed:19801667}.
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_01968,
CC ECO:0000269|PubMed:16905097};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01968,
CC ECO:0000269|PubMed:15780941, ECO:0000269|PubMed:16768447,
CC ECO:0000269|PubMed:16905097};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01968,
CC ECO:0000269|PubMed:15780941, ECO:0000269|PubMed:16768447,
CC ECO:0000269|PubMed:16905097};
CC -!- ACTIVITY REGULATION: Non-competitively inhibited by nicotinamide but
CC not by nicotinic acid. {ECO:0000269|PubMed:15780941}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01968}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class U subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01968}.
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DR EMBL; AE000512; AAD35575.1; -; Genomic_DNA.
DR PIR; A72370; A72370.
DR RefSeq; NP_228300.1; NC_000853.1.
DR PDB; 1YC5; X-ray; 1.40 A; A=1-246.
DR PDB; 2H2D; X-ray; 1.70 A; A=1-246.
DR PDB; 2H2F; X-ray; 2.20 A; A=1-246.
DR PDB; 2H2G; X-ray; 1.63 A; A=1-246.
DR PDB; 2H2H; X-ray; 2.20 A; A=1-246.
DR PDB; 2H2I; X-ray; 1.80 A; A=1-246.
DR PDB; 2H4F; X-ray; 2.00 A; A=1-246.
DR PDB; 2H4H; X-ray; 1.99 A; A=1-246.
DR PDB; 2H4J; X-ray; 2.10 A; A=1-246.
DR PDB; 2H59; X-ray; 1.90 A; A/B=1-246.
DR PDB; 3D4B; X-ray; 1.90 A; A=1-246.
DR PDB; 3D81; X-ray; 2.50 A; A=1-246.
DR PDB; 3JR3; X-ray; 1.50 A; A=1-246.
DR PDB; 3PDH; X-ray; 1.80 A; A=1-246.
DR PDB; 4BUZ; X-ray; 1.90 A; A=1-246.
DR PDB; 4BV2; X-ray; 3.30 A; A/B=1-246.
DR PDBsum; 1YC5; -.
DR PDBsum; 2H2D; -.
DR PDBsum; 2H2F; -.
DR PDBsum; 2H2G; -.
DR PDBsum; 2H2H; -.
DR PDBsum; 2H2I; -.
DR PDBsum; 2H4F; -.
DR PDBsum; 2H4H; -.
DR PDBsum; 2H4J; -.
DR PDBsum; 2H59; -.
DR PDBsum; 3D4B; -.
DR PDBsum; 3D81; -.
DR PDBsum; 3JR3; -.
DR PDBsum; 3PDH; -.
DR PDBsum; 4BUZ; -.
DR PDBsum; 4BV2; -.
DR AlphaFoldDB; Q9WYW0; -.
DR SMR; Q9WYW0; -.
DR DIP; DIP-29141N; -.
DR IntAct; Q9WYW0; 1.
DR STRING; 243274.THEMA_02220; -.
DR ChEMBL; CHEMBL3217404; -.
DR PRIDE; Q9WYW0; -.
DR DNASU; 897531; -.
DR EnsemblBacteria; AAD35575; AAD35575; TM_0490.
DR KEGG; tma:TM0490; -.
DR PATRIC; fig|243274.5.peg.497; -.
DR eggNOG; COG0846; Bacteria.
DR InParanoid; Q9WYW0; -.
DR OMA; ERDCHGL; -.
DR BRENDA; 2.3.1.286; 6331.
DR EvolutionaryTrace; Q9WYW0; -.
DR PRO; PR:Q9WYW0; -.
DR Proteomes; UP000008183; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IBA:GO_Central.
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_01968; Sirtuin_ClassU; 1.
DR IDEAL; IID90011; -.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
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 Transferase; Zinc.
FT CHAIN 1..246
FT /note="NAD-dependent protein deacetylase"
FT /id="PRO_0000110362"
FT DOMAIN 4..246
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01968"
FT ACT_SITE 116
FT /note="Proton acceptor"
FT /evidence="ECO:0000305"
FT BINDING 21..40
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 98..101
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 124
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 127
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 188..190
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 214..216
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 231..232
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT MUTAGEN 33
FT /note="F->A: Reduces kcat for NAD(+), greatly increases
FT sensitivity to nicotinamide inhibition."
FT /evidence="ECO:0000269|PubMed:18786399"
FT MUTAGEN 101
FT /note="D->N: Alters cosubstrate specificity, decreases Km
FT for NAD(+), enzyme unable to discriminate between NAD(+)
FT and nicotinic acid adenine dinucleotide (NAAD)."
FT /evidence="ECO:0000269|PubMed:15780941"
FT MUTAGEN 116
FT /note="H->A: 2-fold decrease in turnover and peptide
FT affinity."
FT /evidence="ECO:0000269|PubMed:16905097"
FT MUTAGEN 116
FT /note="H->Y: 10-fold decrease in turnover and peptide
FT affinity."
FT /evidence="ECO:0000269|PubMed:16905097"
FT MUTAGEN 165
FT /note="N->D: Increased affinity for substrate peptides with
FT a lysine or arginine at position -1."
FT /evidence="ECO:0000269|PubMed:16768447"
FT HELIX 4..12
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 14..20
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2H59"
FT HELIX 38..42
FT /evidence="ECO:0007829|PDB:2H2I"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:3JR3"
FT HELIX 50..55
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 57..67
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 69..73
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 78..88
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 117..124
FT /evidence="ECO:0007829|PDB:1YC5"
FT TURN 125..127
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 133..139
FT /evidence="ECO:0007829|PDB:1YC5"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:3D81"
FT TURN 149..151
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 154..159
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 168..180
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 182..188
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 199..206
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 209..213
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:1YC5"
FT STRAND 225..228
FT /evidence="ECO:0007829|PDB:1YC5"
FT HELIX 232..243
FT /evidence="ECO:0007829|PDB:1YC5"
SQ SEQUENCE 246 AA; 27538 MW; 6BD2EF1B751C190D CRC64;
MKMKEFLDLL NESRLTVTLT GAGISTPSGI PDFRGPNGIY KKYSQNVFDI DFFYSHPEEF
YRFAKEGIFP MLQAKPNLAH VLLAKLEEKG LIEAVITQNI DRLHQRAGSK KVIELHGNVE
EYYCVRCEKK YTVEDVIKKL ESSDVPLCDD CNSLIRPNIV FFGENLPQDA LREAIGLSSR
ASLMIVLGSS LVVYPAAELP LITVRSGGKL VIVNLGETPF DDIATLKYNM DVVEFARRVM
EEGGIS
