NPD_SALTY
ID NPD_SALTY Reviewed; 273 AA.
AC P0A2F2; P97013;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-SEP-2016, sequence version 3.
DT 03-AUG-2022, entry version 99.
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, ECO:0000303|PubMed:8206834};
GN OrderedLocusNames=STM1221;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DISRUPTION PHENOTYPE.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=8955330; DOI=10.1128/jb.178.23.7016-7019.1996;
RA Tsang A.W., Escalante-Semerena J.C.;
RT "cobB function is required for catabolism of propionate in Salmonella
RT typhimurium LT2: evidence for existence of a substitute function for CobB
RT within the 1,2-propanediol utilization (pdu) operon.";
RL J. Bacteriol. 178:7016-7019(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [3]
RP DISRUPTION PHENOTYPE.
RC STRAIN=LT2;
RX PubMed=8206834; DOI=10.1128/jb.176.12.3568-3575.1994;
RA Trzebiatowski J.R., O'Toole G.A., Escalante-Semerena J.C.;
RT "The cobT gene of Salmonella typhimurium encodes the NaMN: 5,6-
RT dimethylbenzimidazole phosphoribosyltransferase responsible for the
RT synthesis of N1-(5-phospho-alpha-D-ribosyl)-5,6-dimethylbenzimidazole, an
RT intermediate in the synthesis of the nucleotide loop of cobalamin.";
RL J. Bacteriol. 176:3568-3575(1994).
RN [4]
RP FUNCTION.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=9822644; DOI=10.1074/jbc.273.48.31788;
RA Tsang A.W., Escalante-Semerena J.C.;
RT "CobB, a new member of the SIR2 family of eucaryotic regulatory proteins,
RT is required to compensate for the lack of nicotinate mononucleotide:5,6-
RT dimethylbenzimidazole phosphoribosyltransferase activity in cobT mutants
RT during cobalamin biosynthesis in Salmonella typhimurium LT2.";
RL J. Biol. Chem. 273:31788-31794(1998).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=12493915; DOI=10.1126/science.1077650;
RA Starai V.J., Celic I., Cole R.N., Boeke J.D., Escalante-Semerena J.C.;
RT "Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of
RT active lysine.";
RL Science 298:2390-2392(2002).
RN [6]
RP FUNCTION AS AN NAD-DEPENDENT DEACETYLASE.
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
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 [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=LT2;
RX PubMed=12700259; DOI=10.1128/jb.185.9.2802-2810.2003;
RA Palacios S., Starai V.J., Escalante-Semerena J.C.;
RT "Propionyl coenzyme A is a common intermediate in the 1,2-propanediol and
RT propionate catabolic pathways needed for expression of the prpBCDE operon
RT during growth of Salmonella enterica on 1,2-propanediol.";
RL J. Bacteriol. 185:2802-2810(2003).
RN [8]
RP FUNCTION, ALTERNATIVE PROMOTER USAGE (ISOFORMS COBB-LONG AND COBB-SHORT),
RP SUBUNIT, INDUCTION, AND MUTAGENESIS OF MET-1 AND 37-MET-MET-38.
RC STRAIN=LT2;
RX PubMed=20889757; DOI=10.1128/jb.00874-10;
RA Tucker A.C., Escalante-Semerena J.C.;
RT "Biologically active isoforms of CobB sirtuin deacetylase in Salmonella
RT enterica and Erwinia amylovora.";
RL J. Bacteriol. 192:6200-6208(2010).
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 (By similarity). Activates
CC the enzyme acetyl-CoA synthetase (acs) by deacetylating 'Lys-609' in
CC the inactive, acetylated form of the enzyme (PubMed:12493915,
CC PubMed:20889757, PubMed:12700259). May also modulate the activity of
CC other propionyl-adenosine monophosphate (AMP)-forming enzymes such as
CC propionate--CoA ligase (prpE) (PubMed:12493915, PubMed:12700259).
CC Overexpression compensates for a cobT deletion, suggesting it may have
CC N(1)-alpha-phosphoribosyltransferase activity; alternatively this
CC protein may stimulate synthesis of an enzyme with the CobT activity
CC (PubMed:9822644). {ECO:0000255|HAMAP-Rule:MF_01121,
CC ECO:0000269|PubMed:10841563, ECO:0000269|PubMed:12493915,
CC ECO:0000269|PubMed:20889757, ECO:0000269|PubMed:9822644,
CC ECO:0000305|PubMed:12700259}.
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 ECO:0000269|PubMed:20889757};
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:0000255|HAMAP-Rule:MF_01121};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01121};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_01121};
CC -!- SUBUNIT: Both isoforms are monomers (PubMed:20889757).
CC {ECO:0000269|PubMed:20889757}.
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:0000269|PubMed:20889757};
CC IsoId=P0A2F2-1; Sequence=Displayed;
CC Name=CobB-Short {ECO:0000269|PubMed:20889757};
CC IsoId=P0A2F2-2; Sequence=VSP_058462;
CC -!- INDUCTION: Most expressed in mid- to late-log growth phases (at protein
CC level) (PubMed:20889757). Has 3 promoters, P1 (upstream of nagK) gives
CC rise to a nagK-cobB transcript, P2 (within the nagK coding region)
CC gives rise to a transcript able to generate both CobB isoforms, while
CC P3 (nucleotide 44 of the long isoform) can only give rise to the CobB-
CC Short isoform (PubMed:20889757). {ECO:0000269|PubMed:20889757}.
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 -!- DISRUPTION PHENOTYPE: Single mutant grows on cobinamide (CBI), CBI plus
CC 5,6-dimethylbenzimidazole (DMB) and cobalamin (CBL); double cobB-cobT
CC deletion mutants do not grow on CBI plus DMB (PubMed:8206834). Single
CC mutant does not grow on propionate (PubMed:8955330). Acetyl-CoA
CC synthetase (acs) accumulates in an inactive, acetylated form
CC (PubMed:12493915). Considerably decreased growth on 1,2-propanediol,
CC cells do not excrete more propanediol than wild-type (PubMed:12700259).
CC {ECO:0000269|PubMed:12493915, ECO:0000269|PubMed:12700259,
CC ECO:0000269|PubMed:8206834, ECO:0000269|PubMed:8955330}.
CC -!- MISCELLANEOUS: Originally isolated genetically as functioning in
CC cobalamin biosynthesis and in propionate catabolism (PubMed:8206834,
CC PubMed:8955330). {ECO:0000305|PubMed:8206834,
CC ECO:0000305|PubMed:8955330}.
CC -!- MISCELLANEOUS: [Isoform CobB-Long]: The less prevalent isoform.
CC {ECO:0000269|PubMed:20889757}.
CC -!- MISCELLANEOUS: [Isoform CobB-Short]: 5- to 20-fold higher levels of
CC this protein are seen in rich and minimal media.
CC {ECO:0000269|PubMed:20889757}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01121}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC78722.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305|PubMed:20889757};
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DR EMBL; U89687; AAC78722.1; ALT_INIT; Genomic_DNA.
DR EMBL; AE006468; AAL20150.1; -; Genomic_DNA.
DR RefSeq; NP_460191.1; NC_003197.2. [P0A2F2-1]
DR RefSeq; WP_001191856.1; NC_003197.2.
DR AlphaFoldDB; P0A2F2; -.
DR SMR; P0A2F2; -.
DR STRING; 99287.STM1221; -.
DR PaxDb; P0A2F2; -.
DR EnsemblBacteria; AAL20150; AAL20150; STM1221.
DR GeneID; 1252739; -.
DR KEGG; stm:STM1221; -.
DR PATRIC; fig|99287.12.peg.1290; -.
DR HOGENOM; CLU_023643_3_1_6; -.
DR OMA; SMQVYPA; -.
DR PhylomeDB; P0A2F2; -.
DR BioCyc; SENT99287:STM1221-MON; -.
DR PHI-base; PHI:5572; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-UniRule.
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; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0036047; P:peptidyl-lysine demalonylation; IBA:GO_Central.
DR GO; GO:0036049; P:peptidyl-lysine desuccinylation; IBA:GO_Central.
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 Alternative promoter usage; Cytoplasm; Metal-binding; NAD;
KW Reference proteome; Transferase; Zinc.
FT CHAIN 1..273
FT /note="NAD-dependent protein deacylase"
FT /id="PRO_0000110348"
FT DOMAIN 1..273
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 BINDING 95
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
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 BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
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 /id="VSP_058462"
FT MUTAGEN 1
FT /note="M->A: Complements a cobB deletion, produces only the
FT short isoform. Has deacylation and
FT phosphoribosyltransferase activities."
FT /evidence="ECO:0000269|PubMed:20889757"
FT MUTAGEN 37..38
FT /note="MM->AA: Complements a cobB deletion, produces only
FT the long isoform. Has deacylation and
FT phosphoribosyltransferase activities."
FT /evidence="ECO:0000269|PubMed:20889757"
FT CONFLICT 115..123
FT /note="KLEEALGDR -> NLKKRLAIA (in Ref. 1; AAC78722)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="H -> Q (in Ref. 1; AAC78722)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="S -> N (in Ref. 1; AAC78722)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 273 AA; 31138 MW; 84DEA78DB7FC403C CRC64;
MQSRRFHRLS RFRKNKRLLR ERLRQRIFFR DRVVPEMMEN PRVLVLTGAG ISAESGIRTF
RAADGLWEEH RVEDVATPEG FARNPGLVQT FYNARRQQLQ QPEIQPNAAH LALAKLEEAL
GDRFLLVTQN IDNLHERAGN RNIIHMHGEL LKVRCSQSGQ ILEWNGDVMP EDKCHCCQFP
APLRPHVVWF GEMPLGMDEI YMALSMADIF IAIGTSGHVY PAAGFVHEAK LHGAHTVELN
LEPSQVGSEF EEKHYGPASQ VVPEFVDKFL KGL