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414  structures 6942  species 0  interactions 19213  sequences 229  architectures

Family: SIR2 (PF02146)

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

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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

  1. North BJ, Verdin E; , Genome Biol 2004;5:224.: Sirtuins: Sir2-related NAD-dependent protein deacetylases. PUBMED:15128440 EPMC:15128440


Internal database links

External database links

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.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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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_2

Alignments

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 View  View  View  View  View  View  View 
HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(18)
Full
(19213)
Representative proteomes UniProt
(58288)
RP15
(3381)
RP35
(8920)
RP55
(16789)
RP75
(25888)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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 Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

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 View help on the curation process

Seed source: IPR003000
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Mian N , Bateman A
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 View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.0 24.0
Trusted cut-off 24.0 24.0
Noise cut-off 23.9 23.9
Model length: 179
Family (HMM) version: 20
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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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...

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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.

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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.

Protein Predicted structure External Information
A0A044RVD9 View 3D Structure Click here
A0A044T4I8 View 3D Structure Click here
A0A044TFQ0 View 3D Structure Click here
A0A044U1C1 View 3D Structure Click here
A0A044V866 View 3D Structure Click here
A0A077YVL7 View 3D Structure Click here
A0A077Z5J0 View 3D Structure Click here
A0A077Z6L0 View 3D Structure Click here
A0A077ZAD6 View 3D Structure Click here
A0A077ZL04 View 3D Structure Click here
A0A0A2V4F8 View 3D Structure Click here
A0A0D2FFX2 View 3D Structure Click here
A0A0D2GHR9 View 3D Structure Click here
A0A0D2GJM3 View 3D Structure Click here
A0A0D2GRF1 View 3D Structure Click here
A0A0D2H300 View 3D Structure Click here
A0A0D2HMQ6 View 3D Structure Click here
A0A0G2JZ79 View 3D Structure Click here
A0A0H3GVK8 View 3D Structure Click here
A0A0H5SD54 View 3D Structure Click here
A0A0J9XZ03 View 3D Structure Click here
A0A0K0DUF7 View 3D Structure Click here
A0A0K0E1Z8 View 3D Structure Click here
A0A0K0EIP1 View 3D Structure Click here
A0A0N4U1Y2 View 3D Structure Click here
A0A0N4U3F0 View 3D Structure Click here
A0A0N4U3H0 View 3D Structure Click here
A0A0N4U6G4 View 3D Structure Click here
A0A0N4UH73 View 3D Structure Click here
A0A0R0EXJ4 View 3D Structure Click here
A0A0R0LEH1 View 3D Structure Click here
A0A0R4IDA4 View 3D Structure Click here
A0A144A2E0 View 3D Structure Click here
A0A175VQC3 View 3D Structure Click here
A0A175VZ73 View 3D Structure Click here
A0A175VZZ6 View 3D Structure Click here
A0A175W1D7 View 3D Structure Click here
A0A175W303 View 3D Structure Click here
A0A175W8D2 View 3D Structure Click here
A0A175WBL4 View 3D Structure Click here