NPD_MYCTU
ID NPD_MYCTU Reviewed; 237 AA.
AC P9WGG3; L0T5V4; O06549; P66813; Q7U0J1;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 40.
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=sir2;
GN OrderedLocusNames=Rv1151c; ORFNames=MTCI65.18c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, CATALYTIC ACTIVITY, AND
RP AUTO-ADP-RIBOSYLATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19747094; DOI=10.1134/s0006297909070062;
RA Gu J., Deng J.Y., Li R., Wei H., Zhang Z., Zhou Y., Zhang Y., Zhang X.E.;
RT "Cloning and characterization of NAD-dependent protein deacetylase
RT (Rv1151c) from Mycobacterium tuberculosis.";
RL Biochemistry (Mosc.) 74:743-748(2009).
RN [3]
RP FUNCTION IN THE DEACETYLATION OF ACSA.
RX PubMed=21896569; DOI=10.1093/abbs/gmr076;
RA Li R., Gu J., Chen P., Zhang Z., Deng J., Zhang X.;
RT "Purification and characterization of the acetyl-CoA synthetase from
RT Mycobacterium tuberculosis.";
RL Acta Biochim. Biophys. Sin. 43:891-899(2011).
RN [4]
RP FUNCTION IN THE DEACETYLATION OF ACSA.
RX PubMed=21627103; DOI=10.1021/bi200156t;
RA Xu H., Hegde S.S., Blanchard J.S.;
RT "Reversible acetylation and inactivation of Mycobacterium tuberculosis
RT acetyl-CoA synthetase is dependent on cAMP.";
RL Biochemistry 50:5883-5892(2011).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP INTERACTION WITH KU AND LIGD, AND SUBUNIT.
RX PubMed=21637345; DOI=10.1371/journal.pone.0020045;
RA Li Z., Wen J., Lin Y., Wang S., Xue P., Zhang Z., Zhou Y., Wang X., Sui L.,
RA Bi L.J., Zhang X.E.;
RT "A Sir2-like protein participates in mycobacterial NHEJ.";
RL PLoS ONE 6:E20045-E20045(2011).
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 (By similarity). Reactivates acetylated acetyl-CoA
CC synthetase (ACS) through an NAD-dependent deacetylation. Is able to
CC ADP-ribosylate itself. {ECO:0000255|HAMAP-Rule:MF_01121,
CC ECO:0000269|PubMed:21627103, ECO:0000269|PubMed:21896569}.
CC -!- FUNCTION: Involved in non-homologous end joining (NHEJ) repair of
CC blunt, 5' overhang and 3' overhang DNA double strand breaks (DSB).
CC {ECO:0000305}.
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:19747094};
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:0000269|PubMed:19747094};
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 -!- ACTIVITY REGULATION: Inhibited by 2-hydroxy-1-naphthaldehyde and
CC nicotinamide. {ECO:0000269|PubMed:19747094}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 9.0. {ECO:0000269|PubMed:19747094};
CC Temperature dependence:
CC Optimum temperature is 25 degrees Celsius.
CC {ECO:0000269|PubMed:19747094};
CC -!- SUBUNIT: Interacts with both Ku and LigD; may form a trimeric complex
CC during NHEJ. {ECO:0000269|PubMed:21637345}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01121}.
CC -!- DOMAIN: 2 residues (Tyr-53 and Arg-56) 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 -!- PTM: Auto-ADP-ribosylated.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01121}.
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DR EMBL; AL123456; CCP43906.1; -; Genomic_DNA.
DR PIR; H70554; H70554.
DR RefSeq; NP_215667.1; NC_000962.3.
DR RefSeq; WP_003406044.1; NZ_NVQJ01000025.1.
DR AlphaFoldDB; P9WGG3; -.
DR SMR; P9WGG3; -.
DR STRING; 83332.Rv1151c; -.
DR PaxDb; P9WGG3; -.
DR DNASU; 886026; -.
DR GeneID; 886026; -.
DR KEGG; mtu:Rv1151c; -.
DR TubercuList; Rv1151c; -.
DR eggNOG; COG0846; Bacteria.
DR OMA; SMQVYPA; -.
DR PhylomeDB; P9WGG3; -.
DR SABIO-RK; P9WGG3; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0070403; F:NAD+ binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003953; F:NAD+ nucleosidase activity; IDA:MTBBASE.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:MTBBASE.
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:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
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:0070213; P:protein auto-ADP-ribosylation; IDA:MTBBASE.
DR GO; GO:0006476; P:protein deacetylation; IDA:MTBBASE.
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 ADP-ribosylation; Cytoplasm; DNA damage; DNA repair; Metal-binding; NAD;
KW Reference proteome; Transferase; Zinc.
FT CHAIN 1..237
FT /note="NAD-dependent protein deacylase"
FT /id="PRO_0000110331"
FT DOMAIN 1..237
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT ACT_SITE 104
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 8..28
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 53
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 56
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 86..89
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 138
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 140
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 177..179
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 203..205
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
FT BINDING 221
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01121"
SQ SEQUENCE 237 AA; 25661 MW; 0D826859B37AFFD7 CRC64;
MRVAVLSGAG ISAESGVPTF RDDKNGLWAR FDPYELSSTQ GWLRNPERVW GWYLWRHYLV
ANVEPNDGHR AIAAWQDHAE VSVITQNVDD LHERAGSGAV HHLHGSLFEF RCARCGVPYT
DALPEMPEPA IEVEPPVCDC GGLIRPDIVW FGEPLPEEPW RSAVEATGSA DVMVVVGTSA
IVYPAAGLPD LALARGTAVI EVNPEPTPLS GSATISIRES ASQALPGLLE RLPALLK
