| IED ID | IndEnz0007000656 |
| Enzyme Type ID | catalase000656 |
| Protein Name |
NAD-dependent protein deacetylase sirtuin-3, mitochondrial hSIRT3 EC 2.3.1.286 Regulatory protein SIR2 homolog 3 SIR2-like protein 3 |
| Gene Name | SIRT3 SIR2L3 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MAFWGWRAAAALRLWGRVVERVEAGGGVGPFQACGCRLVLGGRDDVSAGLRGSHGARGEPLDPARPLQRPPRPEVPRAFRRQPRAAAPSFFFSSIKGGRRSISFSVGASSVVGSGGSSDKGKLSLQDVAELIRARACQRVVVMVGAGISTPSGIPDFRSPGSGLYSNLQQYDLPYPEAIFELPFFFHNPKPFFTLAKELYPGNYKPNVTHYFLRLLHDKGLLLRLYTQNIDGLERVSGIPASKLVEAHGTFASATCTVCQRPFPGEDIRADVMADRVPRCPVCTGVVKPDIVFFGEPLPQRFLLHVVDFPMADLLLILGTSLEVEPFASLTEAVRSSVPRLLINRDLVGPLAWHPRSRDVAQLGDVVHGVESLVELLGWTEEMRDLVQRETGKLDGPDK |
| Enzyme Length | 399 |
| Uniprot Accession Number | Q9NTG7 |
| Absorption | |
| Active Site | ACT_SITE 248; /note="Proton acceptor"; /evidence="ECO:0000269|PubMed:12186850, ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18794531" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide; Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731, ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969, ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767; EC=2.3.1.286; Evidence={ECO:0000255|PROSITE-ProRule:PRU00236, ECO:0000269|PubMed:12186850, ECO:0000269|PubMed:12374852, ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18680753, ECO:0000269|PubMed:18794531, ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:24121500, ECO:0000305|PubMed:23283301}; |
| DNA Binding | |
| EC Number | 2.3.1.286 |
| Enzyme Function | FUNCTION: NAD-dependent protein deacetylase (PubMed:12186850, PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531, PubMed:23283301, PubMed:24121500, PubMed:24252090, PubMed:19535340). Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues (PubMed:12186850, PubMed:12374852, PubMed:16788062, PubMed:18680753, PubMed:18794531, PubMed:23283301, PubMed:24121500, PubMed:24252090). Known targets include ACSS1, IDH, GDH, SOD2, PDHA1, LCAD, SDHA and the ATP synthase subunit ATP5PO (PubMed:16788062, PubMed:18680753, PubMed:24121500, PubMed:24252090, PubMed:19535340). Contributes to the regulation of the cellular energy metabolism (PubMed:24252090). Important for regulating tissue-specific ATP levels (PubMed:18794531). In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription (PubMed:23283301). Acts as a regulator of ceramide metabolism by mediating deacetylation of ceramide synthases CERS1, CERS2 and CERS6, thereby increasing their activity and promoting mitochondrial ceramide accumulation (By similarity). {ECO:0000250|UniProtKB:Q8R104, ECO:0000269|PubMed:12186850, ECO:0000269|PubMed:12374852, ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18680753, ECO:0000269|PubMed:18794531, ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:24121500, ECO:0000269|PubMed:24252090}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 145..165; /note=NAD; /evidence=ECO:0000269|PubMed:23897466; NP_BIND 228..231; /note=NAD; /evidence=ECO:0000269|PubMed:23897466; NP_BIND 319..321; /note=NAD; /evidence=ECO:0000269|PubMed:23897466; NP_BIND 344..346; /note=NAD; /evidence=ECO:0000269|PubMed:23897466 |
| Features | Active site (1); Alternative sequence (1); Beta strand (12); Chain (1); Domain (1); Helix (17); Metal binding (4); Modified residue (1); Mutagenesis (7); Natural variant (3); Nucleotide binding (4); Region (1); Transit peptide (1); Turn (4) |
| Keywords | 3D-structure;Alternative splicing;Metal-binding;Mitochondrion;NAD;Reference proteome;Transferase;Transit peptide;Zinc |
| Interact With | P25705; P28799-2; O60313; Q13309 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000269|PubMed:12186850, ECO:0000269|PubMed:12374852, ECO:0000269|PubMed:16079181, ECO:0000269|PubMed:18215119, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:29445193}. |
| Modified Residue | MOD_RES 122; /note=N6-succinyllysine; /evidence=ECO:0000250|UniProtKB:Q8R104 |
| Post Translational Modification | PTM: Processed by mitochondrial processing peptidase (MPP) to give a 28 kDa product. Such processing is probably essential for its enzymatic activity. {ECO:0000269|PubMed:12186850}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (31) |
| Cross Reference PDB | 3GLR; 3GLS; 3GLT; 3GLU; 4BN4; 4BN5; 4BV3; 4BVB; 4BVE; 4BVF; 4BVG; 4BVH; 4C78; 4C7B; 4FVT; 4FZ3; 4HD8; 4JSR; 4JT8; 4JT9; 4O8Z; 5BWN; 5BWO; 5D7N; 5H4D; 5Y4H; 5YTK; 5Z93; 5Z94; 5ZGC; 6ISO; |
| Mapped Pubmed ID | 12239572; 14976264; 15676284; 16169070; 16189514; 17059877; 17437997; 17715127; 17923681; 17957139; 18710944; 18781224; 19209188; 19240061; 19343720; 19367319; 19680556; 19714312; 20129246; 20132432; 20198340; 20463968; 20661474; 20800603; 20819778; 20877624; 20945913; 21212461; 21358671; 21397863; 21566644; 21701047; 21720390; 22016654; 22155639; 22326535; 22416140; 22585829; 22589271; 22595756; 22609775; 22674009; 22750084; 22770219; 22849721; 23045395; 23046812; 23075334; 23139766; 23185430; 23272146; 23316803; 23397292; 23494737; 23570514; 23665396; 23790338; 23800187; 23839864; 23840057; 23842789; 23856293; 23868064; 23928404; 23956348; 24042441; 24194516; 24211137; 24287180; 24322174; 24324009; 24339251; 24344202; 24464653; 24486017; 24491532; 24503539; 24746213; 24771001; 24774224; 24877629; 24889606; 24909164; 24924131; 25005846; 25007762; 25103363; 25109285; 25128872; 25162939; 25165814; 25194924; 25210848; 25221980; 25227106; 25284742; 25329972; 25361925; 25369635; 25525879; 25562154; 25607838; 25755250; 25755722; 25829495; 25915406; 25915842; 25961022; 26042459; 26045440; 26109058; 26121130; 26121691; 26138757; 26141949; 26223796; 26225774; 26317998; 26456643; 26520405; 26523980; 26577410; 26625292; 26631723; 26667041; 26701732; 26722027; 26743598; 26787646; 26893145; 26950437; 27034011; 27053302; 27078640; 27114304; 27164052; 27216459; 27232755; 27270321; 27277143; 27295248; 27337034; 27367026; 27420645; 27483432; 27501476; 27604398; 27628218; 27731402; 27732568; 27773814; 27815257; 27856259; 27925196; 28032248; 28108513; 28161643; 28197634; 28213977; 28239025; 28258190; 28347248; 28368421; 28429188; 28459202; 28526626; 28536275; 28567457; 28711502; 28717408; 28737710; 28760703; 28867266; 28947845; 29072685; 29130578; 29184120; 29198988; 29220206; 29243781; 29277324; 29323702; 29330215; 29411439; 29421536; 29466723; 29567426; 29574628; 29581566; 29683756; 29898623; 29915029; 30021354; 30091830; 30095923; 30107294; 30126181; 30132870; 30216853; 30250024; 30412732; 30487699; 30572719; 30641770; 30683653; 30691320; 30736780; 30774023; 30829051; 30958373; 30993888; 31037127; 31055111; 31108370; 31153640; 31185214; 31188638; 31189433; 31201798; 31292999; 31677030; 31723239; 31812668; 31894331; 31930676; 31991048; 32195489; 32229158; 32305451; 32329068; 32403131; 32428596; 32462533; 32495859; 32507768; 32681437; 32703935; 32724473; 32747616; 32951306; 33003340; 33115805; 33143333; 33147367; 33160987; 33184465; 33231084; 33241954; 33273545; 33282964; 33423553; 33461161; 33530998; 33565085; 33610576; 33624391; 33655712; 33662874; 33669567; 33706382; 33857259; 33861984; 33872694; 34001853; 34148409; 34232204; 34278469; 34338986; 34363948; 34396428; 34446002; 34500051; 34514931; 34518519; 34630854; 34664305; 34686511; 34747319; 34747550; 34768083; 35195783; |
| Motif | |
| Gene Encoded By | |
| Mass | 43,573 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=600 uM for NAD {ECO:0000269|PubMed:19535340}; |
| Metal Binding | METAL 256; /note="Zinc"; /evidence="ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23897466"; METAL 259; /note="Zinc"; /evidence="ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23897466"; METAL 280; /note="Zinc"; /evidence="ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23897466"; METAL 283; /note="Zinc"; /evidence="ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23897466" |
| Rhea ID | RHEA:43636 |
| Cross Reference Brenda | 2.3.1.24;2.3.1.286; |