SIRTM_STRPG
ID SIRTM_STRPG Reviewed; 293 AA.
AC P0DN71;
DT 20-JAN-2016, integrated into UniProtKB/Swiss-Prot.
DT 20-JAN-2016, sequence version 1.
DT 03-AUG-2022, entry version 22.
DE RecName: Full=Protein ADP-ribosyltransferase {ECO:0000303|PubMed:26166706};
DE EC=2.4.2.- {ECO:0000269|PubMed:26166706};
DE AltName: Full=Sirtuin class M {ECO:0000303|PubMed:26166706};
DE Short=SirTM {ECO:0000303|PubMed:26166706};
GN OrderedLocusNames=SpyM50869 {ECO:0000312|EMBL:CAM30197.1};
OS Streptococcus pyogenes serotype M5 (strain Manfredo).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC Streptococcus.
OX NCBI_TaxID=160491;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Manfredo;
RX PubMed=17012393; DOI=10.1128/jb.01227-06;
RA Holden M.T.G., Scott A., Cherevach I., Chillingworth T., Churcher C.,
RA Cronin A., Dowd L., Feltwell T., Hamlin N., Holroyd S., Jagels K.,
RA Moule S., Mungall K., Quail M.A., Price C., Rabbinowitsch E., Sharp S.,
RA Skelton J., Whitehead S., Barrell B.G., Kehoe M., Parkhill J.;
RT "Complete genome of acute rheumatic fever-associated serotype M5
RT Streptococcus pyogenes strain Manfredo.";
RL J. Bacteriol. 189:1473-1477(2007).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) IN COMPLEXES WITH ZINC; ADP-RIBOSE
RP AND NAD(+), FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, COFACTOR,
RP MUTAGENESIS OF ASN-118; GLN-137 AND ARG-192, AND LACK OF PROTEIN DEACYLASE
RP ACTIVITY.
RC STRAIN=Manfredo;
RX PubMed=26166706; DOI=10.1016/j.molcel.2015.06.013;
RA Rack J.G., Morra R., Barkauskaite E., Kraehenbuehl R., Ariza A., Qu Y.,
RA Ortmayer M., Leidecker O., Cameron D.R., Matic I., Peleg A.Y., Leys D.,
RA Traven A., Ahel I.;
RT "Identification of a class of protein ADP-ribosylating sirtuins in
RT microbial pathogens.";
RL Mol. Cell 59:309-320(2015).
CC -!- FUNCTION: Catalyzes specifically the mono-ADP-ribosylation of GcvH-L
CC (SpyM50867). This activity is dependent on prior lipoylation of the
CC target protein. May be involved in the modulation of the response to
CC host-derived oxidative stress. In contrast to other sirtuin classes,
CC lacks protein deacylase activity, being unable to catalyze
CC debiotinylation, deacetylation and desuccinylation of proteins.
CC {ECO:0000269|PubMed:26166706}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-aspartyl-[protein] + NAD(+) = 4-O-(ADP-D-ribosyl)-L-
CC aspartyl-[protein] + nicotinamide; Xref=Rhea:RHEA:54424, Rhea:RHEA-
CC COMP:9867, Rhea:RHEA-COMP:13832, ChEBI:CHEBI:17154,
CC ChEBI:CHEBI:29961, ChEBI:CHEBI:57540, ChEBI:CHEBI:138102;
CC Evidence={ECO:0000269|PubMed:26166706};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:26166706};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:26166706};
CC -!- MISCELLANEOUS: The SirTM-mediated ADP-ribosylation can be specifically
CC reversed by the Macro domain-containing protein encoded by the same
CC operon (SpyM50868). {ECO:0000269|PubMed:26166706}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class M subfamily.
CC {ECO:0000305|PubMed:26166706}.
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DR EMBL; AM295007; CAM30197.1; -; Genomic_DNA.
DR RefSeq; WP_002992884.1; NC_009332.1.
DR PDB; 5A3A; X-ray; 1.54 A; A=1-293.
DR PDB; 5A3B; X-ray; 1.90 A; A=1-293.
DR PDB; 5A3C; X-ray; 2.03 A; A=1-293.
DR PDBsum; 5A3A; -.
DR PDBsum; 5A3B; -.
DR PDBsum; 5A3C; -.
DR AlphaFoldDB; P0DN71; -.
DR SMR; P0DN71; -.
DR GeneID; 57852685; -.
DR KEGG; spf:SpyM50869; -.
DR HOGENOM; CLU_071599_0_0_9; -.
DR OMA; QGDYGLW; -.
DR GO; GO:0070403; F:NAD+ binding; IDA:UniProtKB.
DR GO; GO:1990404; F:NAD+-protein ADP-ribosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006471; P:protein ADP-ribosylation; IDA:UniProtKB.
DR Gene3D; 3.30.1600.10; -; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Glycosyltransferase; Metal-binding; NAD;
KW Nucleotidyltransferase; Transferase; Zinc.
FT CHAIN 1..293
FT /note="Protein ADP-ribosyltransferase"
FT /id="PRO_0000435344"
FT DOMAIN 16..293
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 34
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26166706"
FT BINDING 117..120
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26166706"
FT BINDING 137
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26166706"
FT BINDING 145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26166706"
FT BINDING 149
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26166706"
FT BINDING 180
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26166706"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:26166706"
FT BINDING 232..234
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26166706"
FT BINDING 258
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26166706"
FT BINDING 262
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26166706"
FT BINDING 279
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26166706"
FT MUTAGEN 118
FT /note="N->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:26166706"
FT MUTAGEN 137
FT /note="Q->H,T: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:26166706"
FT MUTAGEN 192
FT /note="R->A: Dramatic decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:26166706"
SQ SEQUENCE 293 AA; 33985 MW; 8A98CFC27EA1B944 CRC64;
MSNWTTYPQK NLTQAEQLAQ LIKEADALVV GIGAGMSAAD GFTYIGPRFE TAFPDFIAKY
QFLDMLQASL FDFEDWQEYW AFQSRFVALN YLDQPVGQSY LDLKEILETK DYHIITTNAD
NAFWVAGYDP HNIFHIQGEY GLWQCSQHCH QQTYKDDTVI RQMIAEQKNM KVPGQLIPHC
PECEAPFEIN KRNEEKGMVE DADFHAQKAR YEAFLSEHKE GKVLYLEIGV GHTTPQFIKH
PFWKRVSENP NALFVTLNHK HYRIPLSIRR QSLELTEHIA QLISATKTIY QKS
