UniProt functional annotation for Q9NTG7



	UniProt functional annotation for Q9NTG7

UniProt code: Q9NTG7.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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}.

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};

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23897466}; Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23897466};

Biophysicochemical properties: Kinetic parameters: KM=600 uM for NAD {ECO:0000269|PubMed:19535340};

Subunit: Upon metabolic stress, forms a complex composed of FOXO3, SIRT3 and mitochondrial RNA polymerase POLRMT; the complex is recruited to mtDNA in a SIRT3-dependent manner (PubMed:23283301). Also forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT (PubMed:29445193). Interacts with NDUFA9, ACSS1, IDH2 and GDH (PubMed:16788062, PubMed:18794531, PubMed:19535340, PubMed:18680753). Interacts with PCCA (PubMed:23438705). {ECO:0000269|PubMed:16788062, ECO:0000269|PubMed:18680753, ECO:0000269|PubMed:18794531, ECO:0000269|PubMed:19535340, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:23438705, ECO:0000269|PubMed:29445193}.

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}.

Tissue specificity: Widely expressed. {ECO:0000269|PubMed:10381378, ECO:0000269|PubMed:12374852}.

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}.

Miscellaneous: Has some ability to deacetylate histones in vitro, but seeing its subcellular location, this is unlikely in vivo. {ECO:0000269|PubMed:12374852}.

Similarity: Belongs to the sirtuin family. Class I subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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}.


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};
Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269\|PubMed:19535340, ECO:0000269\|PubMed:23897466}; Note=Binds 1 zinc ion per subunit. {ECO:0000269\|PubMed:19535340, ECO:0000269\|PubMed:23897466};
Biophysicochemical properties:		Kinetic parameters: KM=600 uM for NAD {ECO:0000269\|PubMed:19535340};
Subunit:		Upon metabolic stress, forms a complex composed of FOXO3, SIRT3 and mitochondrial RNA polymerase POLRMT; the complex is recruited to mtDNA in a SIRT3-dependent manner (PubMed:23283301). Also forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT (PubMed:29445193). Interacts with NDUFA9, ACSS1, IDH2 and GDH (PubMed:16788062, PubMed:18794531, PubMed:19535340, PubMed:18680753). Interacts with PCCA (PubMed:23438705). {ECO:0000269\|PubMed:16788062, ECO:0000269\|PubMed:18680753, ECO:0000269\|PubMed:18794531, ECO:0000269\|PubMed:19535340, ECO:0000269\|PubMed:23283301, ECO:0000269\|PubMed:23438705, ECO:0000269\|PubMed:29445193}.
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}.
Tissue specificity:		Widely expressed. {ECO:0000269\|PubMed:10381378, ECO:0000269\|PubMed:12374852}.
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}.
Miscellaneous:		Has some ability to deacetylate histones in vitro, but seeing its subcellular location, this is unlikely in vivo. {ECO:0000269\|PubMed:12374852}.
Similarity:		Belongs to the sirtuin family. Class I subfamily. {ECO:0000305}.