NPD_ECOLI
ID NPD_ECOLI Reviewed; 279 AA.
AC P75960;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 07-SEP-2016, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=NAD-dependent protein deacylase {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 {ECO:0000255|HAMAP-Rule:MF_01121};
GN Name=cobB {ECO:0000255|HAMAP-Rule:MF_01121}; Synonyms=ycfY;
GN OrderedLocusNames=b1120, JW1106;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=8905232; DOI=10.1093/dnares/3.3.137;
RA Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K.,
RA Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S.,
RA Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H.,
RA Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G.,
RA Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M.,
RA Horiuchi T.;
RT "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 12.7-28.0 min region on the linkage map.";
RL DNA Res. 3:137-155(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [4]
RP WEAK ADP-RIBOSYLTRANSFERASE ACTIVITY.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=10381378; DOI=10.1006/bbrc.1999.0897;
RA Frye R.A.;
RT "Characterization of five human cDNAs with homology to the yeast SIR2 gene:
RT Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-
RT ribosyltransferase activity.";
RL Biochem. Biophys. Res. Commun. 260:273-279(1999).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=10811920; DOI=10.1073/pnas.110148297;
RA Landry J., Sutton A., Tafrov S.T., Heller R.C., Stebbins J., Pillus L.,
RA Sternglanz R.;
RT "The silencing protein SIR2 and its homologs are NAD-dependent protein
RT deacetylases.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5807-5811(2000).
RN [6]
RP DISCUSSION OF START SITE.
RC STRAIN=K12 / JM109 / ATCC 53323;
RX PubMed=17366475; DOI=10.1002/pmic.200600599;
RA Maillet I., Berndt P., Malo C., Rodriguez S., Brunisholz R.A., Pragai Z.,
RA Arnold S., Langen H., Wyss M.;
RT "From the genome sequence to the proteome and back: evaluation of E. coli
RT genome annotation with a 2-D gel-based proteomics approach.";
RL Proteomics 7:1097-1106(2007).
RN [7]
RP FUNCTION AS A DEACETYLASE AND A DESUCCINYLASE, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, DOMAIN, AND MUTAGENESIS OF TYR-92 AND
RP ARG-95.
RX PubMed=24176774; DOI=10.1074/mcp.m113.031567;
RA Colak G., Xie Z., Zhu A.Y., Dai L., Lu Z., Zhang Y., Wan X., Chen Y.,
RA Cha Y.H., Lin H., Zhao Y., Tan M.;
RT "Identification of lysine succinylation substrates and the succinylation
RT regulatory enzyme CobB in E. coli.";
RL Mol. Cell. Proteomics 12:3509-3520(2013).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 40-274 IN COMPLEX WITH PEPTIDE
RP SUBSTRATE AND ZINC, CATALYTIC ACTIVITY, FUNCTION, SUBSTRATE, INTERACTION
RP WITH ACETYL-COA SYNTHETASE, AND COFACTOR.
RX PubMed=15019790; DOI=10.1016/j.jmb.2004.01.060;
RA Zhao K., Chai X., Marmorstein R.;
RT "Structure and substrate binding properties of cobB, a Sir2 homolog protein
RT deacetylase from Escherichia coli.";
RL J. Mol. Biol. 337:731-741(2004).
RN [9]
RP FUNCTION.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=31328167; DOI=10.1126/sciadv.aaw6703;
RA Dong H., Zhai G., Chen C., Bai X., Tian S., Hu D., Fan E., Zhang K.;
RT "Protein lysine de-2-hydroxyisobutyrylation by CobB in prokaryotes.";
RL Sci. Adv. 5:eaaw6703-eaaw6703(2019).
CC -!- FUNCTION: NAD-dependent lysine deacetylase that specifically removes
CC acetyl groups on target proteins. Also acts as a protein-lysine
CC deacylase by mediating protein desuccinylation and de-2-
CC hydroxyisobutyrylation. Modulates the activities of several proteins
CC which are inactive in their acylated form. Activates the enzyme acetyl-
CC CoA synthetase by deacetylating 'Lys-609' in the inactive, acetylated
CC form of the enzyme. May also modulate the activity of other propionyl-
CC adenosine monophosphate (AMP)-forming enzymes. {ECO:0000255|HAMAP-
CC Rule:MF_01121, ECO:0000269|PubMed:10811920,
CC ECO:0000269|PubMed:15019790, ECO:0000269|PubMed:24176774,
CC ECO:0000269|PubMed:31328167}.
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 -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] + NAD(+) =
CC 2''-O-(2-hydroxyisobutanoyl)-ADP-D-ribose + L-lysyl-[protein] +
CC nicotinamide; Xref=Rhea:RHEA:24364, Rhea:RHEA-COMP:9752, Rhea:RHEA-
CC COMP:15921, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:144968, ChEBI:CHEBI:144969;
CC Evidence={ECO:0000250|UniProtKB:B4EVF5, ECO:0000255|HAMAP-
CC 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:15019790};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01121,
CC ECO:0000269|PubMed:15019790};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15.1 uM for a synthetic histone H3K9 acetyllysine peptide
CC {ECO:0000269|PubMed:24176774};
CC KM=86 uM for a synthetic histone H3K9 succinyllysine peptide
CC {ECO:0000269|PubMed:24176774};
CC Note=kcat is 0.135 sec(-1) for acetyllysine peptide. kcat is 0.242
CC sec(-1) for succinyllysine peptide.;
CC -!- SUBUNIT: Forms a 1:1 complex with acetyl-CoA synthetase (Acs).
CC {ECO:0000269|PubMed:15019790}.
CC -!- INTERACTION:
CC P75960; P75869: sxy; NbExp=9; IntAct=EBI-544459, EBI-544452;
CC P75960; P77376: ydgJ; NbExp=2; IntAct=EBI-544459, EBI-544796;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01121}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=CobB-Long {ECO:0000250|UniProtKB:P0A2F2};
CC IsoId=P75960-1; Sequence=Displayed;
CC Name=CobB-Short {ECO:0000250|UniProtKB:P0A2F2};
CC IsoId=P75960-2; Sequence=VSP_058458;
CC -!- DOMAIN: 2 residues (Tyr-92 and Arg-95) 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 ECO:0000269|PubMed:24176774}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01121}.
CC -!- CAUTION: Was originally thought to be involved in cobalamin
CC biosynthesis. {ECO:0000305}.
CC -!- CAUTION: In contrast to human SIRT5, which has only weak deacetylation
CC activity, CobB shows comparable lysine deacetylation and lysine
CC deacylation activities. {ECO:0000305|PubMed:24176774}.
CC -!- CAUTION: PubMed:10381378 has reported that this protein has a weak ADP-
CC ribosyltransferase activity, but that is probably not its primary
CC activity in vivo. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC74204.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U00096; AAC74204.2; ALT_INIT; Genomic_DNA.
DR EMBL; AP009048; BAA35940.1; -; Genomic_DNA.
DR PIR; E64856; E64856.
DR RefSeq; NP_415638.2; NC_000913.3.
DR RefSeq; WP_000952737.1; NZ_LN832404.1.
DR PDB; 1S5P; X-ray; 1.96 A; A=40-274.
DR PDB; 6RXJ; X-ray; 1.60 A; A/B=40-254.
DR PDB; 6RXK; X-ray; 1.35 A; A=40-279.
DR PDB; 6RXL; X-ray; 2.30 A; A=40-279.
DR PDB; 6RXM; X-ray; 1.92 A; A/B/C/D/E/F=40-279.
DR PDB; 6RXO; X-ray; 1.95 A; A/B=40-279.
DR PDB; 6RXP; X-ray; 1.80 A; A/B=40-279.
DR PDB; 6RXQ; X-ray; 1.70 A; A/B/C/D=40-279.
DR PDB; 6RXR; X-ray; 1.70 A; A/B/C/D=40-279.
DR PDB; 6RXS; X-ray; 1.60 A; A=40-279.
DR PDBsum; 1S5P; -.
DR PDBsum; 6RXJ; -.
DR PDBsum; 6RXK; -.
DR PDBsum; 6RXL; -.
DR PDBsum; 6RXM; -.
DR PDBsum; 6RXO; -.
DR PDBsum; 6RXP; -.
DR PDBsum; 6RXQ; -.
DR PDBsum; 6RXR; -.
DR PDBsum; 6RXS; -.
DR AlphaFoldDB; P75960; -.
DR SMR; P75960; -.
DR BioGRID; 4260089; 21.
DR BioGRID; 850059; 2.
DR DIP; DIP-9301N; -.
DR IntAct; P75960; 19.
DR STRING; 511145.b1120; -.
DR jPOST; P75960; -.
DR PaxDb; P75960; -.
DR PRIDE; P75960; -.
DR EnsemblBacteria; AAC74204; AAC74204; b1120.
DR EnsemblBacteria; BAA35940; BAA35940; BAA35940.
DR GeneID; 945687; -.
DR KEGG; ecj:JW1106; -.
DR KEGG; eco:b1120; -.
DR PATRIC; fig|1411691.4.peg.1147; -.
DR EchoBASE; EB3217; -.
DR eggNOG; COG0846; Bacteria.
DR HOGENOM; CLU_023643_3_1_6; -.
DR InParanoid; P75960; -.
DR OMA; SMQVYPA; -.
DR PhylomeDB; P75960; -.
DR BRENDA; 2.3.1.286; 2026.
DR BRENDA; 2.3.1.B43; 2026.
DR EvolutionaryTrace; P75960; -.
DR PRO; PR:P75960; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0035438; F:cyclic-di-GMP binding; IDA:EcoCyc.
DR GO; GO:0061690; F:lipoamidase activity; IDA:EcoCyc.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IDA:GO_Central.
DR GO; GO:0070403; F:NAD+ binding; IEA:UniProtKB-UniRule.
DR GO; GO:0160013; F:NAD-dependent protein de-2-hydroxyisobutyrylase activity; IEA:RHEA.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:EcoCyc.
DR GO; GO:0061697; F:protein-glutaryllysine deglutarylase activity; IBA:GO_Central.
DR GO; GO:0036054; F:protein-malonyllysine demalonylase activity; IBA:GO_Central.
DR GO; GO:0036055; F:protein-succinyllysine desuccinylase activity; IDA:EcoCyc.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006935; P:chemotaxis; IMP:EcoCyc.
DR GO; GO:0051607; P:defense response to virus; IMP:EcoCyc.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:EcoCyc.
DR GO; GO:0036047; P:peptidyl-lysine demalonylation; IBA:GO_Central.
DR GO; GO:0036049; P:peptidyl-lysine desuccinylation; IDA:EcoCyc.
DR GO; GO:0006476; P:protein deacetylation; IEA:UniProtKB-UniRule.
DR GO; GO:0061698; P:protein deglutarylation; IBA:GO_Central.
DR CDD; cd01412; SIRT5_Af1_CobB; 1.
DR Gene3D; 3.30.1600.10; -; 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 Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; Cytoplasm; Metal-binding; NAD;
KW Reference proteome; Transferase; Zinc.
FT CHAIN 1..279
FT /note="NAD-dependent protein deacylase"
FT /id="PRO_0000110312"
FT DOMAIN 1..274
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT ACT_SITE 147
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 48..67
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 92
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:24176774"
FT BINDING 95
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:24176774"
FT BINDING 129..132
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15019790"
FT BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121,
FT ECO:0000269|PubMed:15019790"
FT BINDING 214..216
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 240..242
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 258
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT VAR_SEQ 1..37
FT /note="Missing (in isoform CobB-Short)"
FT /evidence="ECO:0000250|UniProtKB:P0A2F2"
FT /id="VSP_058458"
FT MUTAGEN 92
FT /note="Y->F: 42-fold decrease in desuccinylase activity. 3-
FT fold decrease in deacetylase activity."
FT /evidence="ECO:0000269|PubMed:24176774"
FT MUTAGEN 95
FT /note="R->M: 100-fold decrease in desuccinylase activity.
FT 3-fold decrease in deacetylase activity."
FT /evidence="ECO:0000269|PubMed:24176774"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 49..55
FT /evidence="ECO:0007829|PDB:6RXK"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 78..83
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 85..99
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 108..120
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:6RXK"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 134..138
FT /evidence="ECO:0007829|PDB:6RXK"
FT STRAND 148..155
FT /evidence="ECO:0007829|PDB:6RXK"
FT TURN 156..158
FT /evidence="ECO:0007829|PDB:6RXK"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:6RXK"
FT STRAND 175..179
FT /evidence="ECO:0007829|PDB:6RXK"
FT STRAND 182..187
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 197..206
FT /evidence="ECO:0007829|PDB:6RXK"
FT STRAND 208..214
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 225..231
FT /evidence="ECO:0007829|PDB:6RXK"
FT STRAND 235..242
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:6RXK"
FT STRAND 251..256
FT /evidence="ECO:0007829|PDB:6RXK"
FT HELIX 258..273
FT /evidence="ECO:0007829|PDB:6RXK"
SQ SEQUENCE 279 AA; 31464 MW; 779CF84961325CB9 CRC64;
MLSRRGHRLS RFRKNKRRLR ERLRQRIFFR DKVVPEAMEK PRVLVLTGAG ISAESGIRTF
RAADGLWEEH RVEDVATPEG FDRDPELVQA FYNARRRQLQ QPEIQPNAAH LALAKLQDAL
GDRFLLVTQN IDNLHERAGN TNVIHMHGEL LKVRCSQSGQ VLDWTGDVTP EDKCHCCQFP
APLRPHVVWF GEMPLGMDEI YMALSMADIF IAIGTSGHVY PAAGFVHEAK LHGAHTVELN
LEPSQVGNEF AEKYYGPASQ VVPEFVEKLL KGLKAGSIA
