SIRT6 - sirtuin 6 Gene

Also Known as SIR2L6; hSIRT6

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 51548

About SIRT6

Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38): 19:4,174,109-4,182,563 (from NCBI)

This gene has 15 transcripts (splice variants), 193 orthologues, 6 paralogues and is associated with 1 phenotype. Ubiquitous expression in colon (RPKM 11.3), spleen (RPKM 5.1) and 25 other tissues.

Summary

This gene encodes a member of the Sirtuin family of NAD-dependent Enzymes that are implicated in cellular stress resistance, genomic stability, aging and energy homeostasis. The encoded protein is localized to the nucleus, exhibits ADP-ribosyl transferase and histone deacetylase activities, and plays a role in DNA repair, maintenance of telomeric chromatin, inflammation, lipid and glucose metabolism. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

SIRT6 Products (10)

mRNA	Protein	Name
NM_001321061.2	NP_001307990.1	NAD-dependent protein deacylase sirtuin-6 isoform 6
NM_001321064.2	NP_001307993.1	NAD-dependent protein deacylase sirtuin-6 isoform 9
NM_001321063.2	NP_001307992.1	NAD-dependent protein deacylase sirtuin-6 isoform 8
NM_001321062.2	NP_001307991.1	NAD-dependent protein deacylase sirtuin-6 isoform 7
NM_001321059.2	NP_001307988.1	NAD-dependent protein deacylase sirtuin-6 isoform 4
NM_001321060.2	NP_001307989.1	NAD-dependent protein deacylase sirtuin-6 isoform 5
NM_001321058.2	NP_001307987.1	NAD-dependent protein deacylase sirtuin-6 isoform 3
XM_024451539.2	XP_024307307.1	NAD-dependent protein deacetylase sirtuin-6 isoform X1
NM_016539.4	NP_057623.2	NAD-dependent protein deacylase sirtuin-6 isoform 1
NM_001193285.3	NP_001180214.1	NAD-dependent protein deacylase sirtuin-6 isoform 2

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables DNA binding	IMP IMP: Inferred from mutant phenotype	33067423	GOA
enables DNA damage sensor activity	IDA IDA: Inferred from direct assay	31995034	GOA
enables NAD+-protein ADP-ribosyltransferase activity	IDA IDA: Inferred from direct assay	21680843	GOA
enables NAD-dependent histone H3K18 deacetylase activity	IDA IDA: Inferred from direct assay	27043296	GOA
enables NAD-dependent histone H3K56 deacetylase activity	IDA IDA: Inferred from direct assay	23911928	GOA
enables NAD-dependent histone H3K9 deacetylase activity	IDA IDA: Inferred from direct assay	18337721	GOA
enables NAD-dependent histone H3K9 deacetylase activity	IMP IMP: Inferred from mutant phenotype	29555651	GOA
enables NAD-dependent histone deacetylase activity	IDA IDA: Inferred from direct assay	24043303	GOA
enables NAD-dependent protein demyristoylase activity	IDA IDA: Inferred from direct assay	23552949	GOA
enables NAD-dependent protein depalmitoylase activity	IDA IDA: Inferred from direct assay	23552949	GOA
enables NAD-dependent protein depalmitoylase activity	IMP IMP: Inferred from mutant phenotype	29555651	GOA
enables NAD-dependent protein lysine deacetylase activity	IDA IDA: Inferred from direct assay	19109893	GOA
enables chromatin DNA binding	IDA IDA: Inferred from direct assay	33067423	GOA
enables chromatin binding	IDA IDA: Inferred from direct assay	27043296	GOA
enables chromatin binding	IMP IMP: Inferred from mutant phenotype	33067423	GOA
enables damaged DNA binding	IDA IDA: Inferred from direct assay	31995034	GOA
enables histone H3K9 deacetylase activity	EXP EXP: Inferred from Experiment	33067423	GOA
enables nucleosome binding	IDA IDA: Inferred from direct assay	23892288	GOA
enables nucleosome binding	IMP IMP: Inferred from mutant phenotype	33067423	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	19135889	GOA
enables protein homodimerization activity	IDA IDA: Inferred from direct assay	31995034	GOA

Biological Process GO Annotation	Evidence	References	Source
involved in chromatin remodeling	IDA IDA: Inferred from direct assay	23892288	GOA
involved in determination of adult lifespan	IMP IMP: Inferred from mutant phenotype	25541994	GOA
involved in double-strand break repair	IDA IDA: Inferred from direct assay	21680843	GOA
involved in negative regulation of cellular senescence	IDA IDA: Inferred from direct assay	22753495	GOA
involved in negative regulation of cellular senescence	IMP IMP: Inferred from mutant phenotype	29474172	GOA
involved in negative regulation of gene expression, epigenetic	IMP IMP: Inferred from mutant phenotype	21847107	GOA
involved in negative regulation of gluconeogenesis	IDA IDA: Inferred from direct assay	23142079	GOA
involved in negative regulation of glycolytic process	IDA IDA: Inferred from direct assay	26456828	GOA
involved in negative regulation of protein localization to chromatin	IDA IDA: Inferred from direct assay	27912097	GOA
involved in negative regulation of transcription by RNA polymerase II	IDA IDA: Inferred from direct assay	24043303	GOA
involved in pericentric heterochromatin formation	IDA IDA: Inferred from direct assay	27043296	GOA
involved in positive regulation of blood vessel branching	IMP IMP: Inferred from mutant phenotype	23201774	GOA
involved in positive regulation of chondrocyte proliferation	IMP IMP: Inferred from mutant phenotype	25819580	GOA
involved in positive regulation of double-strand break repair	IDA IDA: Inferred from direct assay	23911928	GOA
involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP IMP: Inferred from mutant phenotype	27457971	GOA
involved in positive regulation of protein export from nucleus	IDA IDA: Inferred from direct assay	25009184	GOA
involved in positive regulation of stem cell differentiation	IDA IDA: Inferred from direct assay	27912097	GOA
involved in positive regulation of stem cell population maintenance	IDA IDA: Inferred from direct assay	27912097	GOA
involved in positive regulation of telomere maintenance	IMP IMP: Inferred from mutant phenotype	23201774	GOA
involved in positive regulation of vascular endothelial cell proliferation	IMP IMP: Inferred from mutant phenotype	23201774	GOA
involved in protein deacetylation	IMP IMP: Inferred from mutant phenotype	27457971	GOA
involved in protein delipidation	IDA IDA: Inferred from direct assay	23552949	GOA
involved in protein destabilization	IDA IDA: Inferred from direct assay	29474172	GOA
involved in protein destabilization	IMP IMP: Inferred from mutant phenotype	29474172	GOA
involved in protein import into nucleus	IDA IDA: Inferred from direct assay	20117128	GOA
involved in protein import into nucleus	IMP IMP: Inferred from mutant phenotype	20117128	GOA
involved in protein localization to site of double-strand break	IDA IDA: Inferred from direct assay	27568560	GOA
involved in regulation of double-strand break repair via homologous recombination	IDA IDA: Inferred from direct assay	19135889	GOA
involved in regulation of protein localization to plasma membrane	IDA IDA: Inferred from direct assay	28406396	GOA
involved in regulation of protein secretion	IDA IDA: Inferred from direct assay	23552949	GOA
involved in response to UV	IDA IDA: Inferred from direct assay	19109893	GOA
involved in subtelomeric heterochromatin formation	IMP IMP: Inferred from mutant phenotype	21847107	GOA

Cellular Component GO Annotation	Evidence	References	Source
located in chromatin	IDA IDA: Inferred from direct assay	23892288	GOA
located in chromosome, subtelomeric region	IDA IDA: Inferred from direct assay	18337721	GOA
is active in endoplasmic reticulum	IDA IDA: Inferred from direct assay	23552949	GOA
NOT located in nucleolus	IDA IDA: Inferred from direct assay	16079181	GOA
located in nucleoplasm	IDA IDA: Inferred from direct assay	16079181	GOA
is active in nucleus	IDA IDA: Inferred from direct assay	26898756	GOA
located in nucleus	IDA IDA: Inferred from direct assay	25819580	GOA
is active in pericentric heterochromatin	IDA IDA: Inferred from direct assay	27043296	GOA
is active in site of DNA damage	IDA IDA: Inferred from direct assay	19109893	GOA
is active in site of double-strand break	IDA IDA: Inferred from direct assay	21680843	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

SIRT6 Protein Structure

SIR2

0
100
200
300
355 a.a.

Protein Preferred Names	Protein Names
NAD-dependent protein deacylase sirtuin-6 NAD-dependent protein deacetylase sirtuin-6	SIR2-like protein 6 protein mono-ADP-ribosyltransferase sirtuin-6 regulatory protein SIR2 homolog 6 sir2-related protein type 6 sirtuin type 6

Protein Preferred Names

Protein Names

NAD-dependent protein deacylase sirtuin-6

NAD-dependent protein deacetylase sirtuin-6

SIR2-like protein 6
protein mono-ADP-ribosyltransferase sirtuin-6
regulatory protein SIR2 homolog 6
sir2-related protein type 6
sirtuin type 6

SIRT6 Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	SIRT6	Q8N6T7	MYC	Homo sapiens	P01106	Anti Bait CoIP	23217706

Cross: Cross-species interaction Intra: Intraspecies interaction

SIRT6 Antibodies

Cat. No.	Product Name	Application	Reactivity
HY-P80322	SIRT6 Antibody (YA078)	WB, ICC/IF, IHC-P, FC	Human, Mouse
HY-P85522	SIRT6 Antibody (YA5214)	WB, ICC/IF, IP	Human, Mouse, Rat, Monkey

Related Diseases

Diseases	Alias
Premature Menopause	Primary Ovarian Insufficiency Premature Ovarian Failure Hypergonadotropic Hypogonadism Premature Ovarian Insufficiency Menopause - Premature Menopause Praecox Menopause Premature Menopause, Premature Female Hypergonadotropic Hypogonadism Hypergonadotrophic Ovarian Failure Primary Female Hypogonadism Pof - [Premature Ovarian Failure] Ovarian Failure Ovarian Secretion Suppression Ovary Hyposecretion Ovary Secretion Deficiency Premature Menopause Nos
Monckeberg Arteriosclerosis	Monckeberg Medial Calcific Sclerosis
Diabetes Mellitus	Diabetes
Amyotrophic Lateral Sclerosis 1	Amyotrophic Lateral Sclerosis ALS Lou Gehrig Disease Amyotrophic Lateral Sclerosis Type 1 Charcot Disease ALS1 Amyotrophic Lateral Sclerosis, Susceptibility To Fals Lou Gehrig'S Disease Mnd Motor Neuron Disease Familial Amyotrophic Lateral Sclerosis Amyotrophic Lateral Sclerosis 1, Familial Amyotrophic Lateral Sclerosis 1, Autosomal Dominant Motor Neuron Disease, Bulbar Motor Neurone Disease Amyotrophic Lateral Sclerosis With Dementia Dementia With Amyotrophic Lateral Sclerosis Motor Neuron Disease, Amyotrophic Lateral Sclerosis Sclerosis, Lateral, Amyotrophic Sclerosis, Lateral, Amyotrophic, Type 1 Amyotrophic Sclerosis Als - [Amyotrophic Lateral Sclerosis] Wasting Palsy Amyotrophic Paralysis Amyotrophy Lateral Sclerosis Wasting Paralysis Spinal Progressive Amyotrophy Progressive Atrophic Paralysis
Lethal Brain And Heart Developmental Defects
Type 2 Diabetes Mellitus	Insulin Resistance NIDDM Diabetes Mellitus, Non-Insulin-Dependent Type 2 Diabetes T2D Noninsulin-Dependent Diabetes Mellitus Diabetes Mellitus, Type Ii Maturity-Onset Diabetes Insulin Resistance, Severe, Digenic Diabetes Mellitus, Type 2 Diabetes Mellitus, Noninsulin-Dependent Diabetes Mellitus, Noninsulin-Dependent, Association With Diabetes Mellitus, Noninsulin-Dependent, Late Onset Hypertension, Insulin Resistance-Related, Susceptibility To Insulin Resistance, Susceptibility To Non-Insulin-Dependent Diabetes Mellitus Type Ii Diabetes Mellitus Adult-Onset Diabetes Mellitus Maturity-Onset Diabetes Mellitus Diabetes Mellitus Type 2 Type Ii Diabetes Type 2 Diabetes Mellitus, Susceptibility To Diabetes, Type 2 Diabetes Mellitus, Noninsulin-Dependent, Susceptibility To Diabetes Mellitus, Non-Insulin-Dependent, Susceptibility To Diabetes Mellitus, Type 2, Susceptibility To Diabetes Mellitus, Noninsulin-Dependent, 2 Diabetes Mellitus, Type Ii, Susceptibility To Hypertension, Insulin Resistance-Related Adult-Onset Diabetes Aodm Diabetes Mellitus, Adult-Onset Diabetes Mellitus Type Ii Diabetes Mellitus Type 2, Susceptibility To Diabetes, Type Ii, Susceptibility To Diabetes Type 2 Diabetes Mellitus Adult Onset Diabetes Maturity Onset Diabetes Nonketotic Diabetes Non-Insulin Dependent Diabetes Mellitus T2dm - [Type 2 Diabetes Mellitus] Niddm - [Non Insulin Dependent Diabetes Mellitus] Dm2 Dm Type Ii Diabetic Type 2 Insulin Requiring Type 2 Diabetes Noninsulin Dependent Diabetes Non-Insulin-Dependent Diabetes Mellitus Without Complications Diabetes Due To Insulin Secretory Defect Diabetes Mellitus Due To Insulin Secretory Defect Non-Insulin-Dependent Diabetes Of The Young Senile Diabetes Nonketotic Hyperglycaemia Stable Diabetes
Osteoporosis	Postmenopausal Osteoporosis Osteoporosis, Postmenopausal Bone Mineral Density Quantitative Trait Locus Bmnd Osteoporosis, Involutional Osteoporosis, Susceptibility To Osteoporosis, Postmenopausal, Susceptibility Bone Mineral Density Variation Qtl, Osteoporosis OSTEOP Involutional Osteoporosis Senile Osteoporosis Osteoporosis Postmenopausal Bone Mineral Density, Quantitative Trait Locus Osteoporosis, Senile Idiopathic Osteoporosis Bone Rarefaction Nos Type 1 Osteoporosis
Nervous System Disease	Abnormality Of The Nervous System Nervous System Diseases Nervous System Disorder
Non-Alcoholic Fatty Liver Disease	Fatty Liver Non-Alcoholic Fatty Liver Nafld Nonalcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis Steatosis Nafl Nash Non-Alcoholic Steatohepatitis Susceptibility To Nonalcoholic Fatty Liver Disease Steatohepatitis Fatty Degeneration Non-Alcoholic Fatty Liver Disease Without Mention Of Non-Alcoholic Steatohepatitis Nafld Without Nash Nafld Without Mention Of Nash
Pancreatic Cancer	Pancreatic Carcinoma Familial Pancreatic Carcinoma Pancreatic Neoplasm Carcinoma Of Pancreas Pancreatic Carcinoma, Familial Malignant Neoplasm Of Pancreas Pancreatic Acinar Carcinoma Pancreatic Tumor Familial Pancreatic Cancer Neoplasm Of The Pancreas Pancreatic Carcinoma, Somatic Pancreatic Cancer, Somatic Ca Body Of Pancreas Ca Head Of Pancreas Ca Tail Of Pancreas Malignant Neoplasm Of Body Of Pancreas Malignant Neoplasm Of Head Of Pancreas Malignant Neoplasm Of Tail Of Pancreas Pancreas Neoplasm Exocrine Cancer Exocrine Pancreas Carcinoma Hereditary Pancreatic Cancer Hereditary Pancreatic Carcinoma PNCA Cancer Of The Pancreas Pancreatic Cancer, Susceptibility To Carcinoma Of Head Of Pancreas Pancreatic Neoplasms Pancreatic Tumors Cancer, Pancreatic Cancer Of Pancreas Mixed Islet Cell With Exocrine Carcinoma Of Unspecified Site
Body Mass Index Quantitative Trait Locus 11	OBESITY Obesity, Susceptibility To Leanness, Inherited Obesity, Susceptibility To, Bmiq11 Obesity, Mild, Early-Onset Obesity, Association With Obesity, Early-Onset, Susceptibility To Obesity, Severe Obesity, Severe, And Type Ii Diabetes Obesity, Late-Onset BMIQ11 Obesity Bmiq11 Obesity, Early-Onset Obesity , Susceptibility To Simple Obesity Nos Excess Fat Obesity, Not Elsewhere Classified, Body Mass Index Not Elsewhere Classified Adiposis
Parkinson Disease, Late-Onset	Parkinson Disease Parkinson'S Disease PD PARK Parkinson Disease, Susceptibility To Late Onset Parkinson'S Disease Late Onset Parkinson Disease Paralysis Agitans Primary Parkinsonism Idiopathic Parkinson Disease Parkinson'S Parkinson Disease, Late-Onset, Susceptibility To Parkinson Disease, Age Of Onset, Modifier Lewy Body Parkinson Disease Idiopathic Parkinson'S Disease Pd - [Parkinson Disease] Parkinson Disease Nos Parkinson, Nos Primary Parkinson Disease
Aging
Pulpitis	Pulp Stones Pulpitis Nos

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Pre-clinical Phase

Pre-clinical Phase

Bioactive Molecules (17)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-107454	OSS_128167	Inhibitor	98.92%	Unkown
HY-115453	UBCS039	Activator	98.88%	Unkown
HY-N0010	Geniposidic acid	Agonist	98.87%	Unkown
HY-119376	MDL-800	Activator	99.11%	Unkown
HY-148712	SIRT6 activator 12q	Activator	99.83%	Unkown
HY-103721	SIRT6-IN-2	Inhibitor	99.92%	Unkown
HY-156757	MDL-811	Activator	99.68%	Unkown
HY-16605	SIRT6-IN-6	Inhibitor	98.59%	Unkown
HY-156027	SIRT6-IN-3	Inhibitor	98.19%	Unkown
HY-150727	SIRT5 inhibitor 4	Inhibitor	98.37%	Unkown
HY-P3364A	Ac-QPKK(Ac)-AMC acetate	Substrate	99.38%	Unkown
HY-153104	CrBKA		98.46%	Unkown
HY-178990	SIRT6-IN-5	Inhibitor	/	Unkown
HY-170402	SIRT6-IN-4	Inhibitor	/	Unkown
HY-177878	IMU-856	Modulator	/	Unkown
HY-182061	SIRT6 activator 3	Activator	/	Unkown
HY-169159	SIRT6 activator 2	Activator	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Felis catus	SIRT6	VGNC	VGNC:65160
Rattus norvegicus	SIRT6	RGD	RGD:1305216
Bos taurus	SIRT6	VGNC	VGNC:34635
Mus musculus	SIRT6	MGD	MGI:1354161
Canis familiaris	SIRT6	VGNC	VGNC:46187
Macaca mulatta	SIRT6	VGNC	VGNC:77486
Others	SIRT6	NCBI