NDP_MYCS2
ID NDP_MYCS2 Reviewed; 240 AA.
AC A0R2N3;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=NAD-dependent protein deacylase Sir2 {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=sir2; Synonyms=cobB, npdA; OrderedLocusNames=MSMEG_5175, MSMEI_5041;
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP PROTEIN SEQUENCE OF 71-94 AND 219-231, FUNCTION IN NHEJ, INTERACTION WITH
RP KU, SUBUNIT, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
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. {ECO:0000255|HAMAP-Rule:MF_01121}.
CC -!- FUNCTION: Involved in non-homologous end joining (NHEJ) repair of
CC blunt, 5' overhang and 3' overhang DNA double strand breaks (DSB).
CC Overexpression increases the efficiency of NHEJ of the above DSBs 2-
CC fold with no effect on repair fidelity. {ECO:0000269|PubMed:21637345}.
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)-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 -!- 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: 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 -!- DISRUPTION PHENOTYPE: Not essential for growth in the absence of DNA
CC damage. Increased sensitivity to ionizing radiation in log, stationary
CC and late stationary phase. Decreased efficiency of NHEJ on blunt, 5'
CC overhang and 3' overhanging DSB, fidelity the same as for wild-type
CC NHEJ. {ECO:0000269|PubMed:21637345}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class III subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_01121}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CP000480; ABK72526.1; -; Genomic_DNA.
DR EMBL; CP001663; AFP41485.1; -; Genomic_DNA.
DR RefSeq; WP_011730361.1; NZ_SIJM01000038.1.
DR RefSeq; YP_889421.1; NC_008596.1.
DR AlphaFoldDB; A0R2N3; -.
DR SMR; A0R2N3; -.
DR STRING; 246196.MSMEI_5041; -.
DR EnsemblBacteria; ABK72526; ABK72526; MSMEG_5175.
DR EnsemblBacteria; AFP41485; AFP41485; MSMEI_5041.
DR GeneID; 66736490; -.
DR KEGG; msg:MSMEI_5041; -.
DR KEGG; msm:MSMEG_5175; -.
DR PATRIC; fig|246196.19.peg.5049; -.
DR eggNOG; COG0846; Bacteria.
DR OMA; SMQVYPA; -.
DR OrthoDB; 1264438at2; -.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0070403; F:NAD+ binding; IEA:UniProtKB-UniRule.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IEA:UniProtKB-UniRule.
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:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
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; Direct protein sequencing; DNA damage; DNA repair;
KW Metal-binding; NAD; Reference proteome; Transferase; Zinc.
FT CHAIN 1..240
FT /note="NAD-dependent protein deacylase Sir2"
FT /id="PRO_0000425954"
FT DOMAIN 1..240
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 240 AA; 26126 MW; 7CE740A9C5FDE76F CRC64;
MQVTVLSGAG ISAESGVPTF RDAETGLWAQ VDPYEISSTD GWQRNPEKVW AWYLWRHYMM
ARVAPNEAHR TVAAWEDHLD VRVVTQNIDD LHERAGSTNV YHLHGSLFEF RCDACGSAFE
GNLPEMPEPV ETIDPPVCPC SGLIRPSVVW FGEPLPDAAW NRSVLAVSSA DVVIVVGTSS
IVYPAAGLPE AALAAGKPVI EVNPERTPLS DSATVSLRET ASEALPTLLQ RLPELLNRSA
