SIR4_DROME
ID SIR4_DROME Reviewed; 312 AA.
AC Q8IRR5; D0IQB9; Q9W4A1;
DT 16-MAY-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=NAD-dependent protein deacylase Sirt4 {ECO:0000255|HAMAP-Rule:MF_03161};
DE EC=2.3.1.286 {ECO:0000255|HAMAP-Rule:MF_03161};
DE AltName: Full=Regulatory protein SIR2 homolog 4 {ECO:0000255|HAMAP-Rule:MF_03161};
DE Flags: Precursor;
GN Name=Sirt4; ORFNames=CG3187;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.E.;
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Carlson J., Booth B., Frise E., Park S., Wan K., Yu C., Celniker S.E.;
RL Submitted (OCT-2009) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: NAD-dependent protein deacylase. Catalyzes the NAD-dependent
CC hydrolysis of acyl groups from lysine residues. {ECO:0000255|HAMAP-
CC Rule:MF_03161}.
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_03161};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03161};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03161};
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000255|HAMAP-
CC Rule:MF_03161}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=c;
CC IsoId=Q8IRR5-1; Sequence=Displayed;
CC Name=a; Synonyms=b;
CC IsoId=Q8IRR5-2; Sequence=VSP_043535;
CC -!- SIMILARITY: Belongs to the sirtuin family. Class II subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03161}.
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DR EMBL; AE014298; AAF46055.3; -; Genomic_DNA.
DR EMBL; AE014298; AAN09147.2; -; Genomic_DNA.
DR EMBL; AE014298; AAN09146.2; -; Genomic_DNA.
DR EMBL; BT011040; AAR30200.1; -; mRNA.
DR EMBL; BT099555; ACU32639.1; -; mRNA.
DR EMBL; BT100157; ACY07062.1; -; mRNA.
DR RefSeq; NP_572241.2; NM_132013.3. [Q8IRR5-1]
DR RefSeq; NP_727013.2; NM_167041.3. [Q8IRR5-2]
DR RefSeq; NP_727014.2; NM_167042.3. [Q8IRR5-2]
DR AlphaFoldDB; Q8IRR5; -.
DR SMR; Q8IRR5; -.
DR BioGRID; 57986; 29.
DR IntAct; Q8IRR5; 3.
DR STRING; 7227.FBpp0070817; -.
DR PaxDb; Q8IRR5; -.
DR PRIDE; Q8IRR5; -.
DR DNASU; 31480; -.
DR EnsemblMetazoa; FBtr0070850; FBpp0070815; FBgn0029783. [Q8IRR5-2]
DR EnsemblMetazoa; FBtr0070851; FBpp0070816; FBgn0029783. [Q8IRR5-2]
DR EnsemblMetazoa; FBtr0070852; FBpp0070817; FBgn0029783. [Q8IRR5-1]
DR GeneID; 31480; -.
DR KEGG; dme:Dmel_CG3187; -.
DR UCSC; CG3187-RA; d. melanogaster.
DR UCSC; CG3187-RC; d. melanogaster. [Q8IRR5-1]
DR CTD; 23409; -.
DR FlyBase; FBgn0029783; Sirt4.
DR VEuPathDB; VectorBase:FBgn0029783; -.
DR eggNOG; KOG2683; Eukaryota.
DR GeneTree; ENSGT00940000158891; -.
DR HOGENOM; CLU_023643_3_2_1; -.
DR InParanoid; Q8IRR5; -.
DR OMA; RRHYWAR; -.
DR PhylomeDB; Q8IRR5; -.
DR Reactome; R-DME-2151201; Transcriptional activation of mitochondrial biogenesis.
DR SignaLink; Q8IRR5; -.
DR BioGRID-ORCS; 31480; 0 hits in 1 CRISPR screen.
DR ChiTaRS; Sirt4; fly.
DR GenomeRNAi; 31480; -.
DR PRO; PR:Q8IRR5; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0029783; Expressed in ectoderm anlage and 44 other tissues.
DR Genevisible; Q8IRR5; DM.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase.
DR GO; GO:0019213; F:deacetylase activity; IBA:GO_Central.
DR GO; GO:0004407; F:histone deacetylase activity; IMP:FlyBase.
DR GO; GO:0003950; F:NAD+ ADP-ribosyltransferase activity; ISS:FlyBase.
DR GO; GO:0070403; F:NAD+ binding; IEA:UniProtKB-UniRule.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; NAS:FlyBase.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; ISS:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0009267; P:cellular response to starvation; IMP:FlyBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:FlyBase.
DR GO; GO:0016575; P:histone deacetylation; IMP:FlyBase.
DR GO; GO:0006471; P:protein ADP-ribosylation; IEA:UniProtKB-UniRule.
DR GO; GO:0006476; P:protein deacetylation; IBA:GO_Central.
DR Gene3D; 3.30.1600.10; -; 1.
DR HAMAP; MF_01967; Sirtuin_ClassII; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR026587; Sirtuin_class_II.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Metal-binding; Mitochondrion; NAD;
KW Reference proteome; Transferase; Transit peptide; Zinc.
FT TRANSIT 1..16
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT CHAIN 17..312
FT /note="NAD-dependent protein deacylase Sirt4"
FT /id="PRO_0000417347"
FT DOMAIN 36..311
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT ACT_SITE 152
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT BINDING 53..73
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT BINDING 134..137
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT BINDING 163
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT BINDING 214
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT BINDING 251..253
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT BINDING 277..279
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT BINDING 295
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03161"
FT VAR_SEQ 1..83
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_043535"
FT CONFLICT 274
FT /note="G -> A (in Ref. 4; ACY07062)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 312 AA; 34991 MW; A05187624AF8E1B2 CRC64;
MRVGQLLRFR STSLRSSTAR QEYVPHHKPV VEDDIKRLED FLLSKPNVLV LTGAGISTES
GIPDYRSEGV GLYARSNHKP VQHMEFVKSS AVRKRYWARN FVGWPKFSAT QPNATHHALA
RFEREERVQA VVTQNVDRLH TKAGSRNVVE VHGSGYVVKC LSCEYRIDRH EFQSILASLN
PAFKDAPDMI RPDGDVEIPL EYIENFRIPE CTQCGGDLKP EIVFFGDSVP RPRVDQIAGM
VYNSDGLLVL GSSLLVFSGY RVVLQTKDLK LPVGIVNIGE TRADHLADIK ISAKCGDVIP
KLFDFRNSKS VS
