SIR2_TRYB2
ID SIR2_TRYB2 Reviewed; 351 AA.
AC Q57V41; D6XK87; O96670;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=NAD-dependent protein deacetylase SIR2rp1;
DE EC=2.3.1.286;
DE AltName: Full=Regulatory protein SIR2 homolog 1;
DE AltName: Full=SIR2-related protein 1;
GN Name=SIR2rp1; Synonyms=SIR2; ORFNames=Tb927.7.1690;
OS Trypanosoma brucei brucei (strain 927/4 GUTat10.1).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX NCBI_TaxID=185431;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=927/4 GUTat10.1 {ECO:0000312|Proteomes:UP000008524};
RA Hoek M., Wirtz E., Cross G.A.M.;
RT "Cloning of a Trypanosoma brucei Sir2 homolog.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=927/4 GUTat10.1;
RX PubMed=16020726; DOI=10.1126/science.1112642;
RA Berriman M., Ghedin E., Hertz-Fowler C., Blandin G., Renauld H.,
RA Bartholomeu D.C., Lennard N.J., Caler E., Hamlin N.E., Haas B., Bohme U.,
RA Hannick L., Aslett M.A., Shallom J., Marcello L., Hou L., Wickstead B.,
RA Alsmark U.C.M., Arrowsmith C., Atkin R.J., Barron A.J., Bringaud F.,
RA Brooks K., Carrington M., Cherevach I., Chillingworth T.J., Churcher C.,
RA Clark L.N., Corton C.H., Cronin A., Davies R.M., Doggett J., Djikeng A.,
RA Feldblyum T., Field M.C., Fraser A., Goodhead I., Hance Z., Harper D.,
RA Harris B.R., Hauser H., Hostetler J., Ivens A., Jagels K., Johnson D.,
RA Johnson J., Jones K., Kerhornou A.X., Koo H., Larke N., Landfear S.,
RA Larkin C., Leech V., Line A., Lord A., Macleod A., Mooney P.J., Moule S.,
RA Martin D.M., Morgan G.W., Mungall K., Norbertczak H., Ormond D., Pai G.,
RA Peacock C.S., Peterson J., Quail M.A., Rabbinowitsch E., Rajandream M.A.,
RA Reitter C., Salzberg S.L., Sanders M., Schobel S., Sharp S., Simmonds M.,
RA Simpson A.J., Tallon L., Turner C.M., Tait A., Tivey A.R., Van Aken S.,
RA Walker D., Wanless D., Wang S., White B., White O., Whitehead S.,
RA Woodward J., Wortman J., Adams M.D., Embley T.M., Gull K., Ullu E.,
RA Barry J.D., Fairlamb A.H., Opperdoes F., Barrell B.G., Donelson J.E.,
RA Hall N., Fraser C.M., Melville S.E., El-Sayed N.M.A.;
RT "The genome of the African trypanosome Trypanosoma brucei.";
RL Science 309:416-422(2005).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF HIS-142.
RX PubMed=14592982; DOI=10.1093/emboj/cdg553;
RA Garcia-Salcedo J.A., Gijon P., Nolan D.P., Tebabi P., Pays E.;
RT "A chromosomal SIR2 homologue with both histone NAD-dependent ADP-
RT ribosyltransferase and deacetylase activities is involved in DNA repair in
RT Trypanosoma brucei.";
RL EMBO J. 22:5851-5862(2003).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17214740; DOI=10.1111/j.1365-2958.2006.05553.x;
RA Alsford S., Kawahara T., Isamah C., Horn D.;
RT "A sirtuin in the African trypanosome is involved in both DNA repair and
RT telomeric gene silencing but is not required for antigenic variation.";
RL Mol. Microbiol. 63:724-736(2007).
CC -!- FUNCTION: NAD-dependent protein deacetylase, which is involved in
CC repression of RNA polymerase I-mediated expression immediately adjacent
CC to telomeres. It is however not involved in antigenic variation and
CC subtelomeric variant surface glycoprotein (VSG) gene silencing. Plays a
CC role in DNA damage response. Also has ADP-ribosylation activity in
CC vitro. {ECO:0000269|PubMed:14592982, ECO:0000269|PubMed:17214740}.
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|PROSITE-ProRule:PRU00236};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- INTERACTION:
CC Q57V41; Q02539: H1-1; Xeno; NbExp=2; IntAct=EBI-7579996, EBI-932603;
CC Q57V41; P02253: H1-2; Xeno; NbExp=7; IntAct=EBI-7579996, EBI-7580031;
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome, telomere. Note=Co-localizes
CC with telomeres and minichromosomes.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; AF102869; AAC73004.1; -; Genomic_DNA.
DR EMBL; AC159447; AAX70528.1; -; Genomic_DNA.
DR EMBL; CP000070; AAZ12234.1; -; Genomic_DNA.
DR RefSeq; XP_845793.1; XM_840700.1.
DR AlphaFoldDB; Q57V41; -.
DR SMR; Q57V41; -.
DR IntAct; Q57V41; 2.
DR MINT; Q57V41; -.
DR STRING; 5691.AAZ12234; -.
DR PaxDb; Q57V41; -.
DR GeneID; 3658380; -.
DR KEGG; tbr:Tb927.7.1690; -.
DR VEuPathDB; TriTrypDB:Tb927.7.1690; -.
DR eggNOG; KOG2682; Eukaryota.
DR InParanoid; Q57V41; -.
DR OMA; PCSRLPR; -.
DR Proteomes; UP000008524; Chromosome 7.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:0005829; C:cytosol; ISO:GeneDB.
DR GO; GO:0005634; C:nucleus; IDA:GeneDB.
DR GO; GO:0004407; F:histone deacetylase activity; IDA:GeneDB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; IDA:GeneDB.
DR GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:GeneDB.
DR GO; GO:0006281; P:DNA repair; IDA:GeneDB.
DR Gene3D; 3.30.1600.10; -; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR017328; Sirtuin_class_I.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR PIRSF; PIRSF037938; SIR2_euk; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW Chromosome; Metal-binding; NAD; Nucleus; Reference proteome; Repressor;
KW Telomere; Transcription; Transcription regulation; Transferase; Zinc.
FT CHAIN 1..351
FT /note="NAD-dependent protein deacetylase SIR2rp1"
FT /id="PRO_0000417407"
FT DOMAIN 18..327
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 260..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 142
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 37..57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 122..125
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 150
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 153
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 177
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 213..215
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 238..240
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 311
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MUTAGEN 142
FT /note="H->Y: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:14592982"
FT CONFLICT 161
FT /note="M -> I (in Ref. 1; AAC73004)"
FT /evidence="ECO:0000305"
FT CONFLICT 281
FT /note="N -> S (in Ref. 1; AAC73004)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 351 AA; 38575 MW; 046B99AAC661D650 CRC64;
MTEPKLATTH VVGEPTFEGL ARFIERNNIT KIFVMVGAGI SVAAGIPDFR SPHTGLYAKL
SRYNLNSPED AFSLPLLRQQ PSVFYNILMD MDLWPGKYCP TTVHHFISLL AKKGMLLCCC
TQNIDGLERA CGIPESLLVE AHGSFSSASC VDCHAKYDIN MARAETRAGK VPHCNQCGGI
VKPDVVFFGE NLPEAFFNVA GLIEETELLL ILGTSLQVHP FADLALMVPS DVPRVLFNLE
RVGGRMFRFP TDRTPNFRAS SYRLSTGNGN GSKISSGDSS NSSSVDGYDQ FTLAENDETG
VLRDIFFPGD CQVSVRSFAQ ALGFGEQLDA SVREGREIFE RTRRREKVVE G
