SIR2 Week 3

From LMU BioDB 2024
Revision as of 17:31, 31 January 2024 by Asandle1 (talk | contribs) (3D Structure Image not high confidence)
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Summary:

Sir 2 is a member of the Sirtuin family. Sir2 is crucial for cellular function, as it deacetylates nuclear proteins, facilitating telomere formation during cell dormancy and regulating lifespan. It also silences genes at specific chromosomal sites and suppresses early DNA replication, contributing to genome stability. Similar to its mammalian counterpart SIRT1, it regulates autophagy and mitophagy, promoting cellular health. Additionally, it influences chromatin structure through histone deacetylase activity and participates in processes like protein complex localization and metabolic regulation. Found in various cellular regions, including chromosomes and nucleoli, it's part of the RENT complex. Interestingly, it's associated with diseases like Alzheimer's, Parkinson's, diabetes mellitus, and Huntington's disease in humans, with SIRT1 being its counterpart present in humans.


Research indicates that the activity of sirtuin proteins, including Sir2/SIRT1, plays a role in modulating lifespan. One of the primary mechanisms involves the regulation of cellular stress responses and DNA repair processes. Sirtuins are involved in maintaining genomic stability and promoting efficient DNA repair, which are crucial for preventing the accumulation of DNA damage over time.

Sir2 also has been found to regulate key metabolic pathways including glucose, lipid metabolism and mitochondrial function. By regulating these pathways, Sir2 can influence energy production, oxidative stress levels, and overall metabolic health, which impacts lifespan.


NAD-dependent histone deacetylase involved in chromatin assembly, organization and silencing. Also involved in sister chromatid cohesion, double-strand break repair, and the tethering of telomeres at the nuclear periphery (SGD).


   Conserved NAD+ dependent histone deacetylase of the Sirtuin family; deacetylation targets are primarily nuclear proteins; required for telomere hypercluster formation in quiescent yeast cells; involved in regulation of lifespan; plays roles in silencing at HML, HMR, telomeres, and rDNA; negatively regulates initiation of DNA replication; functions as regulator of autophagy like mammalian homolog SIRT1, and also of mitophagy [Source:SGD;Acc:S000002200]


What is the standard name, systematic name, and name description for your gene (from SGD)?

-Standard Name: SIR2 1

-Systematic Name: YDL042C

Description from SGD: Conserved NAD+ dependent histone deacetylase of the Sirtuin family; deacetylation targets are primarily nuclear proteins; required for telomere hypercluster formation in quiescent yeast cells; involved in regulation of lifespan; plays roles in silencing at HML, HMR, telomeres, and rDNA; negatively regulates initiation of DNA replication, suppressing early firing of multicopy rDNA origins; functions as regulator of autophagy like mammalian homolog SIRT1, and also of mitophagy.

What is the gene ID (identifier) for your gene in all four databases (SGD, NCBI Gene, Ensembl, UniProt)?

SGD: S000002200

Uniprot: P06700

Ensembl: YDL042C

NCBI: 851520

Provide hyperlinks to the specific pages for your gene in each of the above databases.

https://www.yeastgenome.org/locus/S000002200

https://www.uniprot.org/uniprotkb/P06700/entry

https://useast.ensembl.org/Saccharomyces_cerevisiae/Gene/Summary?db=core;g=YDL042C;r=IV:376757-378445;t=YDL042C_mRNA

https://www.ncbi.nlm.nih.gov/gene/851520

What is the DNA sequence of your gene?

1 ATGACCATCC CACATATGAA ATACGCCGTA TCAAAGACTA GCGAAAATAA GGTTTCAAAT

 61 ACAGTAAGCC CCACACAAGA TAAAGACGCG ATCAGAAAAC AACCCGATGA CATTATAAAT 
121 AATGATGAAC CTTCACATAA GAAGATAAAA GTAGCACAGC CGGATTCCTT GAGGGAAACC 
181 AACACAACAG ATCCACTTGG GCACACTAAA GCTGCGCTCG GAGAAGTGGC ATCGATGGAG 
241 CTCAAACCAA CTAATGACAT GGATCCCTTG GCAGTGTCAG CAGCTTCAGT AGTGTCAATG 
301 TCCAATGACG TTTTGAAACC AGAGACGCCC AAGGGGCCAA TCATAATCAG TAAAAACCCA 
361 TCAAATGGTA TTTTCTATGG TCCCTCCTTC ACTAAACGAG AGTCTCTCAA TGCTCGAATG 
421 TTTCTGAAAT ACTATGGTGC ACACAAATTT TTAGACACTT ACCTCCCCGA GGATTTGAAC 
481 TCGTTATACA TTTACTATCT TATCAAGTTG CTAGGCTTTG AAGTTAAAGA TCAAGCGCTT 
541 ATCGGCACCA TCAACAGTAT TGTCCATATC AACTCGCAAG AGCGTGTTCA AGATTTGGGA 
601 AGTGCAATAT CTGTCACAAA TGTTGAAGAC CCATTGGCAA AAAAGCAAAC AGTTCGTCTA 
661 ATCAAAGATT TGCAAAGAGC AATTAACAAA GTTCTATGTA CAAGATTAAG ATTATCCAAT 
721 TTTTTCACTA TTGATCATTT TATTCAAAAA TTACATACCG CTAGAAAAAT TTTGGTCCTG 
781 ACTGGTGCAG GTGTTTCAAC TTCATTAGGG ATCCCGGACT TCAGATCTTC TGAGGGGTTC 
841 TATTCAAAGA TCAAACATTT GGGGCTCGAT GATCCCCAAG ACGTTTTCAA TTACAATATA 
901 TTTATGCACG ACCCCTCTGT TTTCTATAAT ATTGCCAATA TGGTTTTACC TCCAGAAAAA 
961 ATTTATTCTC CATTGCATAG TTTCATTAAG ATGCTACAAA TGAAAGGGAA ATTATTGAGA 

1021 AATTATACTC AAAACATTGA TAATTTGGAA TCTTATGCGG GAATAAGCAC AGATAAACTG 1081 GTGCAGTGCC ATGGCTCTTT TGCTACTGCC ACCTGCGTTA CCTGCCATTG GAACCTACCC 1141 GGTGAGAGGA TATTTAATAA AATTAGAAAC CTCGAACTTC CACTATGCCC GTACTGTTAC 1201 AAAAAAAGAA GAGAATATTT CCCAGAGGGA TATAATAATA AAGTAGGTGT TGCTGCATCA 1261 CAGGGTTCAA TGTCGGAAAG GCCTCCATAT ATCCTTAACT CATATGGCGT TCTCAAACCA 1321 GATATCACAT TCTTTGGCGA AGCACTGCCA AATAAATTTC ATAAGAGCAT TCGCGAAGAT 1381 ATCTTAGAAT GTGATTTGTT GATTTGCATT GGGACAAGTT TAAAAGTAGC GCCAGTGTCT 1441 GAAATCGTAA ACATGGTTCC TTCCCACGTT CCCCAAGTCC TGATTAATCG TGATCCCGTC 1501 AAGCACGCAG AATTTGATTT ATCTCTTTTG GGGTACTGTG ATGACATTGC AGCTATGGTA 1561 GCCCAAAAAT GTGGCTGGAC GATTCCGCAT AAGAAATGGA ACGATTTGAA GAACAAGAAC 1621 TTTAAATGCC AAGAGAAGGA TAAGGGCGTG TATGTCGTTA CATCAGATGA ACATCCCAAA 1681 ACCCTCTAA

What is the protein sequence corresponding to your gene?

1 MTIPHMKYAV SKTSENKVSN TVSPTQDKDA IRKQPDDIIN NDEPSHKKIK VAQPDSLRET 
61 NTTDPLGHTK AALGEVASME LKPTNDMDPL AVSAASVVSM SNDVLKPETP KGPIIISKNP 

121 SNGIFYGPSF TKRESLNARM FLKYYGAHKF LDTYLPEDLN SLYIYYLIKL LGFEVKDQAL 181 IGTINSIVHI NSQERVQDLG SAISVTNVED PLAKKQTVRL IKDLQRAINK VLCTRLRLSN 241 FFTIDHFIQK LHTARKILVL TGAGVSTSLG IPDFRSSEGF YSKIKHLGLD DPQDVFNYNI 301 FMHDPSVFYN IANMVLPPEK IYSPLHSFIK MLQMKGKLLR NYTQNIDNLE SYAGISTDKL 361 VQCHGSFATA TCVTCHWNLP GERIFNKIRN LELPLCPYCY KKRREYFPEG YNNKVGVAAS 421 QGSMSERPPY ILNSYGVLKP DITFFGEALP NKFHKSIRED ILECDLLICI GTSLKVAPVS 481 EIVNMVPSHV PQVLINRDPV KHAEFDLSLL GYCDDIAAMV AQKCGWTIPH KKWNDLKNKN 541 FKCQEKDKGV YVVTSDEHPK TL*

Go to the ExPASy tool and translate the DNA sequence of your gene. Which reading frame encodes the protein sequence? Take a screenshot of your results, display it on your wiki page, and state which frame it is.

What is the function of your gene?

Sir2 acts as a NAD+-dependent histone deacetylase. It is involved in gene silencing at specific chromosomal sites like telomeres and loci, and in preserving genomic stability through DNA repair mechanisms. Sir2 influences the regulation of lifespan with increased expression or activity often associated with lifespan extension. It also modulates metabolic pathways such as glucose and lipid metabolism, as well as mitochondrial function, impacting energy generation and cellular health.

What was different about the information provided about your gene in each of the parent databases?

- In one database it included not only the Gene, but the surrounding DNA. (Ensemble)

Were there differences in content, the information or data itself?

Were there differences in presentation of the information?

====Why did you choose your particular gene? i.e., why is it interesting to you and your partner? Include an image related to your gene (be careful that you do not violate any copyright restrictions!)====


Please make the image something scientific (not like the random images seen on the SGD blog posts).

If a 3D structure of the protein your gene encodes is available, you can choose to embed a rotating image of the structure on your page using the FirstGlance in Jmol software. This is optional, a different static image would be OK, too.

The 3D structure of SIR2 is shown on the structure section of it's UniProt entry. The issue is that the Alphafold rendering that is shown is labeled as low confidence, and the x-ray determined structures available from PDB do not show the entire section from positions 1-562, they only show chunks of the positions.

The NCBI Structure database and RSCB Protein Databank also display structures.

Include Acknowledgments and References sections on your wiki page. Both partners should sign the Academic Honesty statement with their wiki signatures.

You need to cite the specific database page from which you derived your information for each of the questions.

Guarente, L. (2013). Calorie restriction and sirtuins revisited. Genes & Development, 27(19), 2072–2085. https://doi.org/10.1101/gad.227439.113 Kennedy, B. K., & Lamming, D. W. (2016). The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging. Cell Metabolism, 23(6), 990–1003. https://doi.org/10.1016/j.cmet.2016.05.009 Bonkowski, M. S., & Sinclair, D. A. (2016). Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nature Reviews Molecular Cell Biology, 17(11), 679–690. https://doi.org/10.1038/nrm.2016.93

https://www.yeastgenome.org/locus/S000002200

https://www.uniprot.org/taxonomy/559292

https://useast.ensembl.org/Saccharomyces_cerevisiae/Gene/Summary?db=core;g=YDL042C;r=IV:376757-378445;t=YDL042C_mRNA

https://www.ncbi.nlm.nih.gov/gene/851520

Except for what is noted above, this individual journal entry was completed by me and not copied from another source. Ckapla12 (talk) 16:13, 31 January 2024 (PST)