| UniProt ID | SIR6_HUMAN | |
|---|---|---|
| UniProt AC | Q8N6T7 | |
| Protein Name | NAD-dependent protein deacetylase sirtuin-6 | |
| Gene Name | SIRT6 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 355 | |
| Subcellular Localization | Nucleus, nucleoplasm . Predominantly nuclear. Associated with telomeric heterochromatin regions. | |
| Protein Description | NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate.. | |
| Protein Sequence | MSVNYAAGLSPYADKGKCGLPEIFDPPEELERKVWELARLVWQSSSVVFHTGAGISTASGIPDFRGPHGVWTMEERGLAPKFDTTFESARPTQTHMALVQLERVGLLRFLVSQNVDGLHVRSGFPRDKLAELHGNMFVEECAKCKTQYVRDTVVGTMGLKATGRLCTVAKARGLRACRGELRDTILDWEDSLPDRDLALADEASRNADLSITLGTSLQIRPSGNLPLATKRRGGRLVIVNLQPTKHDRHADLRIHGYVDEVMTRLMKHLGLEIPAWDGPRVLERALPPLPRPPTPKLEPKEESPTRINGSIPAGPKQEPCAQHNGSEPASPKRERPTSPAPHRPPKRVKAKAVPS | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 2 | Acetylation | ------MSVNYAAGL ------CCCCCCCCC | 21.04 | 19413330 | |
| 2 | Phosphorylation | ------MSVNYAAGL ------CCCCCCCCC | 21.04 | 23186163 | |
| 5 | Phosphorylation | ---MSVNYAAGLSPY ---CCCCCCCCCCCC | 8.82 | 23186163 | |
| 10 | Phosphorylation | VNYAAGLSPYADKGK CCCCCCCCCCCCCCC | 18.23 | 25159151 | |
| 12 | Phosphorylation | YAAGLSPYADKGKCG CCCCCCCCCCCCCCC | 24.85 | 26074081 | |
| 15 | Ubiquitination | GLSPYADKGKCGLPE CCCCCCCCCCCCCCC | 52.69 | - | |
| 17 | Ubiquitination | SPYADKGKCGLPEIF CCCCCCCCCCCCCCC | 30.76 | - | |
| 81 | Ubiquitination | EERGLAPKFDTTFES HHCCCCCCCCCCCCC | 50.71 | - | |
| 128 | Ubiquitination | RSGFPRDKLAELHGN CCCCCHHHHHHHHCC | 51.37 | - | |
| 146 | Phosphorylation | EECAKCKTQYVRDTV HHHHHCCCCEECCCC | 34.30 | - | |
| 148 | Phosphorylation | CAKCKTQYVRDTVVG HHHCCCCEECCCCHH | 11.59 | - | |
| 160 (in isoform 2) | Ubiquitination | - | 37.87 | 21890473 | |
| 160 (in isoform 1) | Ubiquitination | - | 37.87 | 21890473 | |
| 160 | Ubiquitination | VVGTMGLKATGRLCT CHHCCCCCCCCCCHH | 37.87 | 21906983 | |
| 162 | Phosphorylation | GTMGLKATGRLCTVA HCCCCCCCCCCHHHH | 22.65 | - | |
| 167 | Phosphorylation | KATGRLCTVAKARGL CCCCCCHHHHHHHCH | 28.26 | 24719451 | |
| 170 | Ubiquitination | GRLCTVAKARGLRAC CCCHHHHHHHCHHHH | 33.99 | - | |
| 170 | Acetylation | GRLCTVAKARGLRAC CCCHHHHHHHCHHHH | 33.99 | 25953088 | |
| 191 | Phosphorylation | TILDWEDSLPDRDLA HHHCCHHHCCHHHHH | 30.22 | 24719451 | |
| 240 (in isoform 2) | Ubiquitination | - | 23.10 | 21890473 | |
| 245 | Ubiquitination | IVNLQPTKHDRHADL EEECCCCCCCCCCCC | 50.63 | - | |
| 257 | Nitration | ADLRIHGYVDEVMTR CCCEECHHHHHHHHH | 7.20 | - | |
| 267 | Ubiquitination | EVMTRLMKHLGLEIP HHHHHHHHHHCCCCC | 40.03 | 21890473 | |
| 267 (in isoform 1) | Ubiquitination | - | 40.03 | 21890473 | |
| 294 | Phosphorylation | PPLPRPPTPKLEPKE CCCCCCCCCCCCCCC | 35.42 | 30266825 | |
| 303 | Phosphorylation | KLEPKEESPTRINGS CCCCCCCCCCCCCCC | 32.44 | 23927012 | |
| 305 | Phosphorylation | EPKEESPTRINGSIP CCCCCCCCCCCCCCC | 54.16 | 30266825 | |
| 310 | Phosphorylation | SPTRINGSIPAGPKQ CCCCCCCCCCCCCCC | 22.40 | 30266825 | |
| 326 | Phosphorylation | PCAQHNGSEPASPKR CCHHCCCCCCCCCCC | 45.80 | 23401153 | |
| 330 | Phosphorylation | HNGSEPASPKRERPT CCCCCCCCCCCCCCC | 41.49 | 23401153 | |
| 337 | Phosphorylation | SPKRERPTSPAPHRP CCCCCCCCCCCCCCC | 54.27 | 30266825 | |
| 338 | Phosphorylation | PKRERPTSPAPHRPP CCCCCCCCCCCCCCC | 23.03 | 30266825 |
| Modified Location | Modified Residue | Modification | Function | Reference | ||
|---|---|---|---|---|---|---|
Oops, there are no descriptions of PTM sites of SIR6_HUMAN !! | ||||||
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of SIR6_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| There are no disease associations of PTM sites. | ||||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| Phosphorylation | |
| Reference | PubMed |
| "Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND MASSSPECTROMETRY. | |
| "A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-294 AND SER-303, ANDMASS SPECTROMETRY. | |
