NPD_PROMH
ID NPD_PROMH Reviewed; 285 AA.
AC B4EVF5;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 96.
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, ECO:0000269|PubMed:31328167};
DE AltName: Full=Regulatory protein SIR2 homolog {ECO:0000255|HAMAP-Rule:MF_01121};
GN Name=npdA {ECO:0000312|EMBL:CAR41984.1};
GN Synonyms=cobB {ECO:0000255|HAMAP-Rule:MF_01121,
GN ECO:0000303|PubMed:31328167};
GN OrderedLocusNames=PMI0881 {ECO:0000312|EMBL:CAR41984.1};
OS Proteus mirabilis (strain HI4320).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Morganellaceae; Proteus.
OX NCBI_TaxID=529507;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=HI4320;
RX PubMed=18375554; DOI=10.1128/jb.01981-07;
RA Pearson M.M., Sebaihia M., Churcher C., Quail M.A., Seshasayee A.S.,
RA Luscombe N.M., Abdellah Z., Arrosmith C., Atkin B., Chillingworth T.,
RA Hauser H., Jagels K., Moule S., Mungall K., Norbertczak H.,
RA Rabbinowitsch E., Walker D., Whithead S., Thomson N.R., Rather P.N.,
RA Parkhill J., Mobley H.L.T.;
RT "Complete genome sequence of uropathogenic Proteus mirabilis, a master of
RT both adherence and motility.";
RL J. Bacteriol. 190:4027-4037(2008).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF TYR-94 AND ARG-97.
RC STRAIN=ATCC 29906;
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. Catalyzes deacetylation and
CC de-2-hydroxyisobutyrylation of Eno at 'Lys-326' and 'Lys-343',
CC respectively, thereby promoting the enolase activity.
CC {ECO:0000255|HAMAP-Rule:MF_01121, 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 ECO:0000305|PubMed:31328167};
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 ECO:0000305|PubMed:31328167};
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:0000269|PubMed:31328167};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13.3 uM for a N6-(2-hydroxyisobutyryl)lysine peptide
CC {ECO:0000269|PubMed:31328167};
CC Note=kcat is 0.225 sec(-1) for a N6-(2-hydroxyisobutyryl)lysine
CC peptide. {ECO:0000269|PubMed:31328167};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01121}.
CC -!- DOMAIN: 2 residues (Tyr-94 and Arg-97) present in a large hydrophobic
CC pocket are probably involved in substrate specificity. They are
CC important for deacylation activity, but dispensable for deacetylation
CC activity. {ECO:0000255|HAMAP-Rule:MF_01121}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01121}.
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DR EMBL; AM942759; CAR41984.1; -; Genomic_DNA.
DR RefSeq; WP_004247834.1; NC_010554.1.
DR STRING; 529507.PMI0881; -.
DR EnsemblBacteria; CAR41984; CAR41984; PMI0881.
DR GeneID; 6799909; -.
DR KEGG; pmr:PMI0881; -.
DR eggNOG; COG0846; Bacteria.
DR HOGENOM; CLU_023643_3_1_6; -.
DR OMA; SMQVYPA; -.
DR Proteomes; UP000008319; 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; IDA:UniProtKB.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:UniProtKB.
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:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006476; P:protein deacetylation; IEA:UniProtKB-UniRule.
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 Cytoplasm; Metal-binding; NAD; Reference proteome; Transferase; Zinc.
FT CHAIN 1..285
FT /note="NAD-dependent protein deacylase"
FT /id="PRO_0000454795"
FT DOMAIN 30..277
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 50..69
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 94
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 97
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 132..135
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 158
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 177
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 217..219
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 243..245
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 261
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT MUTAGEN 94
FT /note="Y->F: Does not affect activity toward a N6-(2-
FT hydroxyisobutyryl)lysine peptide."
FT /evidence="ECO:0000269|PubMed:31328167"
FT MUTAGEN 97
FT /note="R->M: Strongly decreased activity toward a N6-(2-
FT hydroxyisobutyryl)lysine peptide."
FT /evidence="ECO:0000269|PubMed:31328167"
SQ SEQUENCE 285 AA; 32895 MW; E9D218C64C374A12 CRC64;
MMKLKLRHRR LRKFRKIKSL RRQHSRCRYF HLTHKTEHEM NLPKVVVLTG AGISAESGIK
TFRSEDGLWE EHRVEDVATP EGYHRNPKLV QQFYNERRRQ LQQPSIQPNE AHYALAKLEQ
YLGKDNFLLV TQNIDNLHEK AGSKHILHMH GELLKVRCPQ SGQVFEWKGD LSTTDYCHCC
QFPSPLRPHI VWFGEMPIGM DEIYHALAQA DLFIAIGTSG NVYPAAGFVH EARLTGAHTV
ELNLEPSLVE SEFEEKHYGP ASQVVDAYVH KLFDLINDPK ADLTQ
