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SIRT6
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  • SIRT6
PROTEIN SUMMARY SECTION OVERVIEW RNA DATA ANTIBODY DATA
Amygdala Basal ganglia Thalamus Midbrain Pons Medulla oblongata Hippocampal formation Spinal cord White matter Cerebral cortex Cerebellum Choroid plexus Hypothalamus Retina Thyroid gland Parathyroid gland Adrenal gland Pituitary gland Lung Salivary gland Esophagus Tongue Stomach Rectum Duodenum Small intestine Colon Liver Gallbladder Pancreas Kidney Urinary bladder Testis Epididymis Prostate Seminal vesicle Vagina Breast Cervix Endometrium Fallopian tube Ovary Placenta Heart muscle Skeletal muscle Smooth muscle Adipose tissue Skin Bone marrow Tonsil Thymus Lymph node Appendix Spleen
SIRT6 INFORMATION
Proteini

Full gene name according to HGNC.

Sirtuin 6
Gene namei

Official gene symbol, which is typically a short form of the gene name, according to HGNC.

SIRT6
Protein classi

Assigned HPA protein class(es) for the encoded protein(s).

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Enzymes
Metabolic proteins
Number of transcriptsi

Number of protein-coding transcripts from the gene as defined by Ensembl.

6
Protein evidence Evidence at protein level (all genes)
PROTEIN EXPRESSION AND LOCALIZATION
Tissue profilei

A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue section.

"Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.
Ubiquitous nuclear expression.
Subcellular location Localized to the Nucleoplasm In addition localized to the Vesicles
Predicted locationi

All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.

  • Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.

  • Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).

The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.

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Intracellular
TISSUE RNA EXPRESSION
Tissue specificityi

The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.

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Low tissue specificity
Tissue expression clusteri

The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

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Intestine - Brush border (mainly)
Brain specificityi

The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category

Read more
Low human brain regional specificity
Single cell type specificityi

The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.

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Cell type enhanced (Distal enterocytes)
Single cell type
expression clusteri

The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Read more
Enterocytes - Absorption (mainly)
Tissue cell type classificationi

Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.

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Cell type enriched (Adipose visceral - Adipose progenitor cells)
IMMUNE CELLS
Immune cell specificityi

The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.

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Low immune cell specificity
Immune cell
expression clusteri

The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Read more
Eosinophils - Transcription (mainly)
CANCER & CELL LINES
Prognostic summary Prognostic marker in urothelial cancer (favorable), endometrial cancer (favorable) and stomach cancer (favorable) Urothelial cancer p<0.001
Cancer specificityi

Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.

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Low cancer specificity
Cell line
expression clusteri

The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Read more
Non-specific - mRNA processing (mainly)
Cell line specificityi

RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.

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Low cancer specificity
PROTEINS IN BLOOD
Detected in blood by
immunoassayi

The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.

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No (not applicable)
Detected in blood by
mass spectrometryi

Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.

No
Detected in blood by
proximity extension assayi

Detection or not of the gene in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with three visits during two years.

Read more
No
PROTEIN FUNCTION
Protein function (UniProt)i

Useful information about the protein provided by UniProt.

NAD-dependent protein deacetylase, deacylase and mono-ADP-ribosyltransferase that plays an essential role in DNA damage repair, telomere maintenance, metabolic homeostasis, inflammation, tumorigenesis and aging 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13. Displays protein-lysine deacetylase or defatty-acylase (demyristoylase and depalmitoylase) activity, depending on the context 14, 15, 16. Acts as a key histone deacetylase by catalyzing deacetylation of histone H3 at 'Lys-9', 'Lys-18' and 'Lys-56' (H3K9ac, H3K18ac and H3K56ac, respectively), suppressing target gene expression of several transcription factors, including NF-kappa-B 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27. Acts as an inhibitor of transcription elongation by mediating deacetylation of H3K9ac and H3K56ac, preventing release of NELFE from chromatin and causing transcriptional pausing (By similarity). Involved in DNA repair by promoting double-strand break (DSB) repair: acts as a DSB sensor by recognizing and binding DSB sites, leading to (1) recruitment of DNA repair proteins, such as SMARCA5/SNF2H, and (2) deacetylation of histone H3K9ac and H3K56ac 28, 29, 30. SIRT6 participation to DSB repair is probably involved in extension of life span (By similarity). Also promotes DNA repair by deacetylating non-histone proteins, such as DDB2 and p53/TP53 31, 32. Specifically deacetylates H3K18ac at pericentric heterochromatin, thereby maintaining pericentric heterochromatin silencing at centromeres and protecting against genomic instability and cellular senescence 33. Involved in telomere maintenance by catalyzing deacetylation of histone H3 in telomeric chromatin, regulating telomere position effect and telomere movement in response to DNA damage 34, 35, 36. Required for embryonic stem cell differentiation by mediating histone deacetylation of H3K9ac 37, 38. Plays a major role in metabolism by regulating processes such as glycolysis, gluconeogenesis, insulin secretion and lipid metabolism 39, 40. Inhibits glycolysis via histone deacetylase activity and by acting as a corepressor of the transcription factor HIF1A, thereby controlling the expression of multiple glycolytic genes (By similarity). Has tumor suppressor activity by repressing glycolysis, thereby inhibiting the Warburg effect 41. Also regulates glycolysis and tumorigenesis by mediating deacetylation and nuclear export of non-histone proteins, such as isoform M2 of PKM (PKM2) 42. Acts as a negative regulator of gluconeogenesis by mediating deacetylation of non-histone proteins, such as FOXO1 and KAT2A/GCN5 43, 44. Promotes beta-oxidation of fatty acids during fasting by catalyzing deacetylation of NCOA2, inducing coactivation of PPARA (By similarity). Acts as a regulator of lipid catabolism in brown adipocytes, both by catalyzing deacetylation of histones and non-histone proteins, such as FOXO1 (By similarity). Also acts as a regulator of circadian rhythms, both by regulating expression of clock-controlled genes involved in lipid and carbohydrate metabolism, and by catalyzing deacetylation of PER2 (By similarity). The defatty-acylase activity is specifically involved in regulation of protein secretion 45, 46, 47, 48. Has high activity toward long-chain fatty acyl groups and mediates protein-lysine demyristoylation and depalmitoylation of target proteins, such as RRAS2 and TNF, thereby regulating their secretion 49, 50. Also acts as a mono-ADP-ribosyltransferase by mediating mono-ADP-ribosylation of PARP1, TRIM28/KAP1 or SMARCC2/BAF170 51, 52, 53, 54. Mono-ADP-ribosyltransferase activity is involved in DNA repair, cellular senescence, repression of LINE-1 retrotransposon elements and regulation of transcription 55, 56, 57.... show less
Molecular function (UniProt)i

Keywords assigned by UniProt to proteins due to their particular molecular function.

Acyltransferase, Chromatin regulator, Developmental protein, DNA-binding, Glycosyltransferase, Nucleotidyltransferase, RNA-binding, Transferase
Biological process (UniProt)i

Keywords assigned by UniProt to proteins because they are involved in a particular biological process.

DNA damage, DNA repair
Disease involvementi

Disease related keywords assigned by UniProt combined with Cancer-related genes and FDA approved drug targets

Read more
Disease variant, Tumor suppressor
Ligand (UniProt)i

Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.

Metal-binding, NAD, Zinc
Gene summary (Entrez)i

Useful information about the gene from Entrez

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]... show less

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