Summary: Sir2 family
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "Sirtuin". More...
Sirtuin Edit Wikipedia article
Redirect to:
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Sir2 family Provide feedback
This region is characteristic of Silent information regulator 2 (Sir2) proteins, or sirtuins. These are protein deacetylases that depend on nicotine adenine dinucleotide (NAD). They are found in many subcellular locations, including the nucleus, cytoplasm and mitochondria. Eukaryotic forms play in important role in the regulation of transcriptional repression. Moreover, they are involved in microtubule organisation and DNA damage repair processes [1].i
Literature references
-
North BJ, Verdin E; , Genome Biol 2004;5:224.: Sirtuins: Sir2-related NAD-dependent protein deacetylases. PUBMED:15128440 EPMC:15128440
Internal database links
SCOOP: | PNTB TPP_enzyme_M |
External database links
PROSITE profile: | PS50305 |
SCOP: | 1j8f |
This tab holds annotation information from the InterPro database.
InterPro entry IPR003000
The sirtuin (also known as Sir2) family is broadly conserved from bacteria to human. Yeast Sir2 (silent mating-type information regulation 2), the founding member, was first isolated as part of the SIR complex required for maintaining a modified chromatin structure at telomeres. Sir2 functions in transcriptional silencing, cell cycle progression, and chromosome stability [ PUBMED:7498786 ]. Although most sirtuins in eukaryotic cells are located in the nucleus, others are cytoplasmic or mitochondrial.
This family is divided into five classes (I-IV and U) on the basis of a phylogenetic analysis of 60 sirtuins from a wide array of organisms [ PUBMED:10873683 ]. Class I and class IV are further divided into three and two subgroups, respectively. The U-class sirtuins are found only in Gram-positive bacteria [ PUBMED:10873683 ]. The S. cerevisiae genome encodes five sirtuins, Sir2 and four additional proteins termed 'homologues of sir two' (Hst1p-Hst4p) [ PUBMED:7498786 ]. The human genome encodes seven sirtuins, with representatives from classes I-IV [ PUBMED:10873683 , PUBMED:15128440 ].
Sirtuins are responsible for a newly classified chemical reaction, NAD-dependent protein deacetylation. The final products of the reaction are the deacetylated peptide and an acetyl ADP-ribose [ PUBMED:11747420 ]. In nuclear sirtuins this deacetylation reaction is mainly directed against histones acetylated lysines [ PUBMED:11722841 ].
Sirtuins typically consist of two optional and highly variable N- and C- terminal domain (50-300 aa) and a conserved catalytic core domain (~250 aa). Mutagenesis experiments suggest that the N- and C-terminal regions help direct catalytic core domain to different targets [ PUBMED:11722841 , PUBMED:10381378 ].
The 3D-structure of an archaeal sirtuin in complex with NAD reveals that the protein consists of a large domain having a Rossmann fold and a small domain containing a three-stranded zinc ribbon motif. NAD is bound in a pocket between the two domains [ PUBMED:11336676 ].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Molecular function | NAD+ binding (GO:0070403) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
Loading domain graphics...
Pfam Clan
This family is a member of clan FAD_DHS (CL0085), which has the following description:
The members of this family adopt a Rossmann fold, similar to CLAN:CL0063. However, the members of this family are distinguished in that the FAD/NAD cofactor is bound in the opposite direction. In this arrangement, the adenosine moiety is found bound at the second half of the fold. In addition, the conserved GxGxxG motif found in classical NADP binding Rossmann folds is absent. Finally, another distinguishing characteristic is the formation of an internal hydrogen bond in the FAD molecule [1].
The clan contains the following 10 members:
CO_dh DS DUF4917 ETF_alpha PNTB PPS_PS SIR2 SIR2_2 TPP_enzyme_M TPP_enzyme_M_2Alignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
View options
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
Seed (18) |
Full (19213) |
Representative proteomes | UniProt (58288) |
||||
---|---|---|---|---|---|---|---|
RP15 (3381) |
RP35 (8920) |
RP55 (16789) |
RP75 (25888) |
||||
Jalview | |||||||
HTML | |||||||
PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
Format an alignment
Download options
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
Seed (18) |
Full (19213) |
Representative proteomes | UniProt (58288) |
||||
---|---|---|---|---|---|---|---|
RP15 (3381) |
RP35 (8920) |
RP55 (16789) |
RP75 (25888) |
||||
Raw Stockholm | |||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
Seed source: | IPR003000 |
Previous IDs: | none |
Type: | Family |
Sequence Ontology: | SO:0100021 |
Author: |
Mian N |
Number in seed: | 18 |
Number in full: | 19213 |
Average length of the domain: | 170.6 aa |
Average identity of full alignment: | 28 % |
Average coverage of the sequence by the domain: | 51.98 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|
||||||||||||
Model details: |
|
||||||||||||
Model length: | 179 | ||||||||||||
Family (HMM) version: | 20 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
Sunburst controls
HideWeight segments by...
Change the size of the sunburst
Colour assignments
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
Selections
Generate a FASTA-format file
Clear selection
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...
Tree controls
HideThe tree shows the occurrence of this domain across different species. More...
Loading...
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the SIR2 domain has been found. There are 414 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
Loading structure mapping...
AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.