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484  structures 2790  species 0  interactions 53102  sequences 1395  architectures

Family: SET (PF00856)

Summary: SET domain

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This is the Wikipedia entry entitled "SET domain". More...

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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.

SET domain Provide feedback

SET domains are protein lysine methyltransferase enzymes. SET domains appear to be protein-protein interaction domains. It has been demonstrated that SET domains mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases) [2]. A subset of SET domains have been called PR domains. These domains are divergent in sequence from other SET domains, but also appear to mediate protein-protein interaction [3]. The SET domain consists of two regions known as SET-N and SET-C. SET-C forms an unusual and conserved knot-like structure of probably functional importance. Additionally to SET-N and SET-C, an insert region (SET-I) and flanking regions of high structural variability form part of the overall structure [5].

Literature references

  1. Tripoulas N, LaJeunesse D, Gildea J, Shearn A; , Genetics 1996;143:913-928.: The Drosophila ash1 gene product, which is localized at specific sites on polytene chromosomes, contains a SET domain and a PHD finger. PUBMED:8725238 EPMC:8725238

  2. Cui X, De Vivo I, Slany R, Miyamoto A, Firestein R, Cleary ML; , Nat Genet 1998;18:331-337.: Association of SET domain and myotubularin-related proteins modulates growth control. PUBMED:9537414 EPMC:9537414

  3. Huang S, Shao G, Liu L; , J Biol Chem 1998;273:15933-15939.: The PR domain of the Rb-binding zinc finger protein RIZ1 is a protein binding interface and is related to the SET domain functioning in chromatin-mediated gene expression. PUBMED:9632640 EPMC:9632640

  4. Min J, Zhang X, Cheng X, Grewal SI, Xu RM; , Nat Struct Biol 2002;0:0-0.: Structure of the SET domain histone lysine methyltransferase Clr4. PUBMED:12389037 EPMC:12389037

  5. Marmorstein R; , Trends Biochem Sci 2003;28:59-62.: Structure of SET domain proteins: a new twist on histone methylation. PUBMED:12575990 EPMC:12575990


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001214

The SET domain is a 130 to 140 amino acid, evolutionary well conserved sequence motif that was initially characterised in the Drosophila proteins Su(var)3-9, Enhancer-of-zeste and Trithorax. In addition to these chromosomal proteins modulating gene activities and/or chromatin structure, the SET domain is found in proteins of diverse functions ranging from yeast to mammals, but also including some bacteria and viruses [ PUBMED:9487389 , PUBMED:10949293 ].

The SET domains of mammalian SUV39H1 and 2 and fission yeast clr4 have been shown to be necessary for the methylation of lysine-9 in the histone H3 N terminus [ PUBMED:10949293 ]. However, this histone methyltransferase (HMTase) activity is probably restricted to a subset of SET domain proteins as it requires the combination of the SET domain with the adjacent cysteine-rich regions, one located N-terminally (pre-SET) and the other posterior to the SET domain (post-SET). Post- and pre- SET regions seem then to play a crucial role when it comes to substrate recognition and enzymatic activity [ PUBMED:12826405 , PUBMED:12372294 ].

The structure of the SET domain and the two adjacent regions pre-SET and post-SET have been solved [ PUBMED:12372305 , PUBMED:12372304 , PUBMED:12372303 ]. The SET structure is all beta, but consists only in sets of few short strands composing no more than a couple of small sheets. Consequently the SET structure is mostly defined by turns and loops. An unusual feature is that the SET core is made up of two discontinual segments of the primary sequence forming an approximate L shape [ PUBMED:9632640 , PUBMED:12826405 , PUBMED:12372294 ]. Two of the most conserved motifs in the SET domain are constituted by (1) a stretch at the C-terminal containing a strictly conserved tyrosine residue and (2) a preceding loop inside which the C-terminal segment passes forming a knot-like structure, but not quite a true knot. These two regions have been proven to be essential for SAM binding and catalysis, particularly the invariant tyrosine where in all likelihood catalysis takes place [ PUBMED:12826405 , PUBMED:12372294 ].

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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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...

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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
(257)
Full
(53102)
Representative proteomes UniProt
(92834)
RP15
(9429)
RP35
(23088)
RP55
(41319)
RP75
(56268)
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PP/heatmap 1            

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

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

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  Seed
(257)
Full
(53102)
Representative proteomes UniProt
(92834)
RP15
(9429)
RP35
(23088)
RP55
(41319)
RP75
(56268)
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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
(257)
Full
(53102)
Representative proteomes UniProt
(92834)
RP15
(9429)
RP35
(23088)
RP55
(41319)
RP75
(56268)
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: [1]
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bateman A , Huang S
Number in seed: 257
Number in full: 53102
Average length of the domain: 159.30 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 17.94 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.4 22.4
Trusted cut-off 22.4 22.4
Noise cut-off 22.3 22.3
Model length: 169
Family (HMM) version: 31
Download: download the raw HMM for this family

Species distribution

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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 SET domain has been found. There are 484 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
A0A096MJU6 View 3D Structure Click here
A0A0G2JTW4 View 3D Structure Click here
A0A0G2JW37 View 3D Structure Click here
A0A0G2JWF0 View 3D Structure Click here
A0A0G2K001 View 3D Structure Click here
A0A0G2K5A7 View 3D Structure Click here
A0A0G2K6T6 View 3D Structure Click here
A0A0G2K889 View 3D Structure Click here
A0A0G2KB10 View 3D Structure Click here
A0A0P0V8S0 View 3D Structure Click here
A0A0P0VDF3 View 3D Structure Click here
A0A0P0VDJ3 View 3D Structure Click here
A0A0P0VE60 View 3D Structure Click here
A0A0P0VK92 View 3D Structure Click here
A0A0P0WFA2 View 3D Structure Click here
A0A0P0XCN3 View 3D Structure Click here
A0A0P0XDC9 View 3D Structure Click here
A0A0P0XQ57 View 3D Structure Click here
A0A0P0XYC1 View 3D Structure Click here
A0A0P0Y6F9 View 3D Structure Click here
A0A0R0EIG0 View 3D Structure Click here
A0A0R0ELD1 View 3D Structure Click here
A0A0R0EM36 View 3D Structure Click here
A0A0R0EQU1 View 3D Structure Click here
A0A0R0ET93 View 3D Structure Click here
A0A0R0EZ91 View 3D Structure Click here
A0A0R0FUI7 View 3D Structure Click here
A0A0R0G0Z4 View 3D Structure Click here
A0A0R0GH45 View 3D Structure Click here
A0A0R0GL68 View 3D Structure Click here
A0A0R0GZF1 View 3D Structure Click here
A0A0R0HD21 View 3D Structure Click here
A0A0R0I0W2 View 3D Structure Click here
A0A0R0I2D0 View 3D Structure Click here
A0A0R0I3Y4 View 3D Structure Click here
A0A0R0I6N1 View 3D Structure Click here
A0A0R0IGL3 View 3D Structure Click here
A0A0R0JEA7 View 3D Structure Click here
A0A0R0JKQ3 View 3D Structure Click here
A0A0R0KTU7 View 3D Structure Click here