3K35

Crystal Structure of Human SIRT6

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
D	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8063732	3001728	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8063732	3001728	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8063732	3001728	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8063732	3001728	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8063732	3001728	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	DHS-like NAD/FAD-binding domain	8063732	3001728	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
D	SIR2_1st	e3k35D2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: SIR2_1st	ECOD (1.6)
D	KOG1905	e3k35D3	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: KOG1905	ECOD (1.6)
A	SIR2_1st	e3k35A2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: SIR2_1st	ECOD (1.6)
A	KOG1905	e3k35A3	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: KOG1905	ECOD (1.6)
B	SIR2_1st	e3k35B2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: SIR2_1st	ECOD (1.6)
B	KOG1905	e3k35B3	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: KOG1905	ECOD (1.6)
C	SIR2_1st	e3k35C2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: SIR2_1st	ECOD (1.6)
C	KOG1905	e3k35C3	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: KOG1905	ECOD (1.6)
E	SIR2_1st	e3k35E2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: SIR2_1st	ECOD (1.6)
E	KOG1905	e3k35E3	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: KOG1905	ECOD (1.6)
F	SIR2_1st	e3k35F2	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: DHS-like NAD/FAD-binding domain	F: SIR2_1st	ECOD (1.6)
F	KOG1905	e3k35F3	A: few secondary structure elements	X: Rubredoxin-like	H: Rubredoxin-related	T: Rubredoxin-related	F: KOG1905	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
D	3.40.50.1220	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	TPP-binding domain	CATH (4.3.0)
D	2.20.28.200	Mainly Beta	Single Sheet	Rubrerythrin, domain 2		CATH (4.3.0)
A	3.40.50.1220	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	TPP-binding domain	CATH (4.3.0)
A	2.20.28.200	Mainly Beta	Single Sheet	Rubrerythrin, domain 2		CATH (4.3.0)
B	3.40.50.1220	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	TPP-binding domain	CATH (4.3.0)
B	2.20.28.200	Mainly Beta	Single Sheet	Rubrerythrin, domain 2		CATH (4.3.0)
C	3.40.50.1220	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	TPP-binding domain	CATH (4.3.0)
C	2.20.28.200	Mainly Beta	Single Sheet	Rubrerythrin, domain 2		CATH (4.3.0)
E	3.40.50.1220	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	TPP-binding domain	CATH (4.3.0)
E	2.20.28.200	Mainly Beta	Single Sheet	Rubrerythrin, domain 2		CATH (4.3.0)
F	3.40.50.1220	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	TPP-binding domain	CATH (4.3.0)
F	2.20.28.200	Mainly Beta	Single Sheet	Rubrerythrin, domain 2		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D, E A, B, C, D, E, F	PF02146	Sir2 family (SIR2)	Sir2 family	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D, E A, B, C, D, E, F	NAD-dependent deacetylase sirtuin-6	NAD+ ADP-ribosyltransferase activity pentosyltransferase activity glycosyltransferase activity transferase activity catalytic activity RNA binding binding organic cyclic compound binding lncRNA binding nucleic acid binding deacetylase activity protein lysine deacetylase activity catalytic activity, acting on a protein NAD-dependent protein lysine deacetylase activity NAD+ ADP-ribosyltransferase activity pentosyltransferase activity glycosyltransferase activity transferase activity catalytic activity RNA binding binding organic cyclic compound binding lncRNA binding nucleic acid binding deacetylase activity protein lysine deacetylase activity catalytic activity, acting on a protein NAD-dependent protein lysine deacetylase activity hydrolase activity NAD-dependent histone deacetylase activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds NAD-dependent histone H3K56 deacetylase activity histone deacetylase activity histone H3K deacetylase activity histone modifying activity NAD-dependent histone H3K18 deacetylase activity protein-containing complex binding TORC2 complex binding NAD+ binding NAD binding nucleotide binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding adenyl nucleotide binding heterocyclic compound binding small molecule binding NAD+-protein-arginine ADP-ribosyltransferase activity NAD+-protein ADP-ribosyltransferase activity NAD+- protein-lysine ADP-ribosyltransferase activity DNA damage sensor activity small molecule sensor activity NAD-dependent protein demyristoylase activity acyltransferase activity acyltransferase activity, transferring groups other than amino-acyl groups chromatin binding NAD-dependent histone H3K9 deacetylase activity histone H3K9 deacetylase activity DNA binding damaged DNA binding transcription corepressor activity transcription regulator activity transcription coregulator activity protein-macromolecule adaptor activity molecular adaptor activity identical protein binding protein binding protein homodimerization activity protein dimerization activity chromatin DNA binding cation binding transition metal ion binding zinc ion binding metal ion binding nucleotidyltransferase activity transferase activity, transferring phosphorus-containing groups NAD-dependent protein depalmitoylase activity nucleosome binding	protein localization negative regulation of protein transport regulation of localization establishment of protein localization negative regulation of nucleocytoplasmic transport nitrogen compound transport regulation of cellular process nucleocytoplasmic transport nuclear transport negative regulation of biological process negative regulation of intracellular protein transport negative regulation of transport localization import into nucleus cellular macromolecule localization protein localization negative regulation of protein transport regulation of localization establishment of protein localization negative regulation of nucleocytoplasmic transport nitrogen compound transport regulation of cellular process nucleocytoplasmic transport nuclear transport negative regulation of biological process negative regulation of intracellular protein transport negative regulation of transport localization import into nucleus cellular macromolecule localization establishment of localization in cell regulation of intracellular transport regulation of biological process organic substance transport negative regulation of establishment of protein localization intracellular transport regulation of nucleocytoplasmic transport protein localization to nucleus establishment of localization establishment of protein localization to organelle regulation of intracellular protein transport intracellular protein transport cellular localization regulation of protein localization transport regulation of protein localization to nucleus negative regulation of protein import into nucleus regulation of protein import into nucleus protein import into nucleus negative regulation of cellular process negative regulation of protein localization negative regulation of intracellular transport regulation of transport biological regulation regulation of establishment of protein localization regulation of protein transport negative regulation of protein localization to nucleus protein transport regulation of cellular localization macromolecule localization protein localization to organelle cellular process cellular response to stimulus regulation of DNA recombination regulation of double-strand break repair response to stimulus regulation of cellular response to stress regulation of primary metabolic process nucleobase-containing compound metabolic process organic substance metabolic process cellular response to stress response to stress regulation of response to stress recombinational repair regulation of nucleobase-containing compound metabolic process double-strand break repair via homologous recombination DNA repair double-strand break repair DNA recombination primary metabolic process DNA metabolic process regulation of macromolecule metabolic process nucleic acid metabolic process regulation of DNA repair regulation of double-strand break repair via homologous recombination organic cyclic compound metabolic process DNA damage response regulation of response to stimulus metabolic process macromolecule metabolic process regulation of metabolic process regulation of DNA metabolic process protein destabilization regulation of protein stability regulation of biological quality protein localization to extracellular region regulation of secretion by cell secretion by cell secretion establishment of protein localization to extracellular region export from cell protein secretion regulation of protein secretion regulation of secretion retrotransposon silencing transposition retrotransposition DNA repair-dependent chromatin remodeling protein-containing complex organization protein-DNA complex organization cellular component organization chromatin organization chromatin remodeling cellular component organization or biogenesis pyridine nucleotide catabolic process oxoacid metabolic process carbohydrate catabolic process organophosphate catabolic process carbohydrate derivative metabolic process regulation of generation of precursor metabolites and energy nucleoside phosphate catabolic process organic acid metabolic process regulation of ATP metabolic process regulation of purine nucleotide catabolic process negative regulation of nucleotide metabolic process regulation of small molecule metabolic process regulation of nucleotide metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process small molecule metabolic process purine ribonucleotide catabolic process negative regulation of carbohydrate metabolic process nucleoside phosphate metabolic process organonitrogen compound catabolic process pyruvate metabolic process cellular metabolic process negative regulation of metabolic process negative regulation of purine nucleotide catabolic process purine nucleoside diphosphate metabolic process purine-containing compound catabolic process regulation of purine nucleotide metabolic process nucleobase-containing compound catabolic process nucleoside diphosphate metabolic process regulation of phosphorus metabolic process monocarboxylic acid metabolic process pyridine-containing compound catabolic process ribose phosphate metabolic process ATP metabolic process negative regulation of purine nucleotide metabolic process negative regulation of phosphate metabolic process nucleobase-containing small molecule metabolic process purine ribonucleoside triphosphate metabolic process negative regulation of nucleotide catabolic process purine nucleotide catabolic process carbohydrate derivative catabolic process organic cyclic compound catabolic process purine-containing compound metabolic process ADP metabolic process negative regulation of phosphorus metabolic process purine ribonucleoside diphosphate metabolic process organic substance catabolic process purine ribonucleoside diphosphate catabolic process ribonucleotide catabolic process negative regulation of small molecule metabolic process negative regulation of glycolytic process negative regulation of ATP metabolic process negative regulation of cellular metabolic process glycolytic process pyridine-containing compound metabolic process negative regulation of nucleobase-containing compound metabolic process phosphorus metabolic process pyridine nucleotide metabolic process nicotinamide nucleotide metabolic process regulation of carbohydrate catabolic process regulation of cellular metabolic process nucleotide metabolic process purine nucleoside diphosphate catabolic process nucleoside diphosphate catabolic process regulation of nucleotide catabolic process nucleoside triphosphate metabolic process purine ribonucleotide metabolic process catabolic process purine nucleotide metabolic process ribonucleotide metabolic process ribonucleoside diphosphate metabolic process ribonucleoside diphosphate catabolic process regulation of carbohydrate metabolic process nucleotide catabolic process ribonucleoside triphosphate metabolic process negative regulation of catabolic process purine nucleoside triphosphate metabolic process carbohydrate metabolic process organonitrogen compound metabolic process ADP catabolic process carboxylic acid metabolic process regulation of catabolic process generation of precursor metabolites and energy regulation of glycolytic process organophosphate metabolic process developmental process heart development multicellular organismal process cellular developmental process cardiac muscle tissue development cardiac muscle cell differentiation animal organ development muscle cell differentiation tissue development cardiocyte differentiation striated muscle tissue development circulatory system development muscle structure development multicellular organism development cell differentiation anatomical structure development striated muscle cell differentiation muscle tissue development system development negative regulation of transcription elongation by RNA polymerase II negative regulation of RNA biosynthetic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II organic substance biosynthetic process regulation of DNA-templated transcription elongation negative regulation of DNA-templated transcription regulation of transcription elongation by RNA polymerase II negative regulation of cellular biosynthetic process negative regulation of DNA-templated transcription, elongation regulation of gene expression biosynthetic process negative regulation of macromolecule biosynthetic process organic cyclic compound biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process transcription elongation by RNA polymerase II cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process DNA-templated transcription elongation negative regulation of biosynthetic process heterochromatin formation epigenetic regulation of gene expression pericentric heterochromatin formation negative regulation of gene expression constitutive heterochromatin formation negative regulation of gene expression, epigenetic protein localization to chromosome protein localization to site of double-strand break positive regulation of proteasomal protein catabolic process positive regulation of protein metabolic process proteolysis involved in protein catabolic process positive regulation of biological process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process regulation of ubiquitin-dependent protein catabolic process positive regulation of metabolic process positive regulation of ubiquitin-dependent protein catabolic process regulation of proteolysis regulation of proteolysis involved in protein catabolic process modification-dependent macromolecule catabolic process proteolysis positive regulation of macromolecule metabolic process protein metabolic process regulation of protein metabolic process proteasomal protein catabolic process protein catabolic process positive regulation of protein catabolic process positive regulation of proteolysis involved in protein catabolic process positive regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process positive regulation of proteolysis regulation of proteasomal protein catabolic process positive regulation of proteasomal ubiquitin-dependent protein catabolic process ubiquitin-dependent protein catabolic process regulation of protein catabolic process regulation of stem cell proliferation cell population proliferation positive regulation of cell population proliferation positive regulation of stem cell proliferation stem cell proliferation regulation of cell population proliferation positive regulation of cellular process rhythmic process circadian regulation of gene expression circadian rhythm positive regulation of chondrocyte proliferation chondrocyte proliferation endothelial cell proliferation positive regulation of epithelial cell proliferation regulation of vascular endothelial cell proliferation regulation of endothelial cell proliferation positive regulation of endothelial cell proliferation vascular endothelial cell proliferation regulation of epithelial cell proliferation epithelial cell proliferation positive regulation of vascular endothelial cell proliferation macromolecule deacylation protein deacetylation protein deacylation macromolecule modification protein modification process response to light stimulus response to radiation response to abiotic stimulus response to UV subtelomeric heterochromatin formation telomere organization chromosome organization organelle organization base-excision repair small molecule biosynthetic process cellular ketone metabolic process ketone biosynthetic process positive regulation of organelle organization regulation of telomere maintenance regulation of cellular component organization positive regulation of cellular component organization positive regulation of telomere maintenance positive regulation of nucleobase-containing compound metabolic process regulation of chromosome organization regulation of organelle organization positive regulation of chromosome organization telomere maintenance positive regulation of DNA metabolic process protein localization to cell periphery protein localization to plasma membrane localization within membrane regulation of protein localization to cell periphery protein localization to membrane regulation of protein localization to plasma membrane regulation of protein localization to membrane regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II fat cell differentiation positive regulation of fat cell differentiation regulation of developmental process regulation of cell differentiation positive regulation of developmental process positive regulation of cell differentiation regulation of fat cell differentiation chemical homeostasis homeostatic process glucose homeostasis carbohydrate homeostasis positive regulation of response to stimulus positive regulation of DNA repair positive regulation of double-strand break repair regulation of lipid metabolic process lipid metabolic process regulation of circadian rhythm fibroblast proliferation regulation of fibroblast proliferation positive regulation of fibroblast proliferation hexose transmembrane transport glucose import carbohydrate transport negative regulation of transmembrane transport glucose transmembrane transport regulation of glucose import transmembrane transport negative regulation of glucose import regulation of glucose transmembrane transport negative regulation of glucose transmembrane transport regulation of transmembrane transport monosaccharide transmembrane transport carbohydrate transmembrane transport regulation of stem cell population maintenance stem cell population maintenance positive regulation of stem cell population maintenance positive regulation of multicellular organismal process regulation of multicellular organismal process maintenance of cell number lipid catabolic process regulation of lipid catabolic process protein localization to chromatin negative regulation of protein localization to chromatin regulation of protein localization to chromatin adaptive thermogenesis multicellular organismal-level homeostasis regulation of cold-induced thermogenesis cold-induced thermogenesis temperature homeostasis positive regulation of cold-induced thermogenesis positive regulation of nucleocytoplasmic transport positive regulation of establishment of protein localization positive regulation of protein transport positive regulation of intracellular transport nuclear export regulation of protein export from nucleus protein export from nucleus positive regulation of protein export from nucleus positive regulation of transport positive regulation of protein localization positive regulation of intracellular protein transport determination of adult lifespan branching morphogenesis of an epithelial tube angiogenesis regulation of vasculature development tube morphogenesis positive regulation of morphogenesis of an epithelium regulation of morphogenesis of an epithelium epithelial tube morphogenesis regulation of anatomical structure morphogenesis blood vessel development regulation of morphogenesis of a branching structure epithelium development regulation of multicellular organismal development blood vessel morphogenesis tube development morphogenesis of an epithelium positive regulation of angiogenesis regulation of blood vessel branching vasculature development positive regulation of blood vessel branching branching involved in blood vessel morphogenesis tissue morphogenesis anatomical structure morphogenesis positive regulation of vasculature development regulation of angiogenesis morphogenesis of a branching structure anatomical structure formation involved in morphogenesis morphogenesis of a branching epithelium positive regulation of stem cell differentiation stem cell differentiation regulation of stem cell differentiation protein delipidation negative regulation of cell population proliferation regulation of cellular senescence cellular senescence negative regulation of cellular senescence monosaccharide metabolic process gluconeogenesis negative regulation of gluconeogenesis regulation of glucose metabolic process carbohydrate biosynthetic process hexose metabolic process monosaccharide biosynthetic process hexose biosynthetic process regulation of gluconeogenesis regulation of carbohydrate biosynthetic process glucose metabolic process positive regulation of protein localization to chromatin positive regulation of cell communication cell communication positive regulation of insulin secretion regulation of peptide hormone secretion regulation of hormone levels positive regulation of peptide hormone secretion regulation of hormone secretion regulation of peptide secretion signaling positive regulation of secretion by cell hormone secretion peptide secretion positive regulation of hormone secretion positive regulation of secretion amide transport signal release positive regulation of peptide secretion regulation of signaling regulation of peptide transport cell-cell signaling positive regulation of protein secretion peptide transport regulation of insulin secretion peptide hormone secretion hormone transport regulation of cell communication insulin secretion positive regulation of signaling	intracellular organelle protein-containing complex intracellular anatomical structure protein-DNA complex organelle intracellular non-membrane-bounded organelle chromatin chromosome cellular anatomical entity non-membrane-bounded organelle membrane-bounded organelle intracellular membrane-bounded organelle nucleus membrane-enclosed lumen intracellular organelle protein-containing complex intracellular anatomical structure protein-DNA complex organelle intracellular non-membrane-bounded organelle chromatin chromosome cellular anatomical entity non-membrane-bounded organelle membrane-bounded organelle intracellular membrane-bounded organelle nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen chromosome, subtelomeric region chromosome, telomeric region chromosomal region pericentric heterochromatin heterochromatin chromosome, centromeric region site of double-strand break site of DNA damage endoplasmic reticulum cytoplasm endomembrane system

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D, E A, B, C, D, E, F	IPR003000	Sirtuin family	Family
A, B, C, D, E A, B, C, D, E, F	IPR029035	DHS-like NAD/FAD-binding domain superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F	IPR026590	Sirtuin family, catalytic core domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D, E A, B, C, D, E, F	Pharos: Q8N6T7	Cardiomegaly atypical teratoid rhabdoid tumor large cell medulloblastoma cancer ovarian cancer glioblastoma

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.