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0  structures 839  species 0  interactions 11658  sequences 210  architectures

Family: Exostosin (PF03016)

Summary: Exostosin family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

The Pfam group coordinates the annotation of Pfam families in Wikipedia, but we have not yet assigned a Wikipedia article to this family. If you think that a particular Wikipedia article provides good annotation, please let us know.

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.

Exostosin family Provide feedback

The EXT family is a family of tumour suppressor genes. Mutations of EXT1 Q16394 on 8q24.1, EXT2 Q93063 on 11p11-13, and EXT3 on 19p have been associated with the autosomal dominant disorder known as hereditary multiple exostoses (HME). This is the most common known skeletal dysplasia. The chromosomal locations of other EXT genes suggest association with other forms of neoplasia. EXT1 and EXT2 have both been shown to encode a heparan sulphate polymerase with both D-glucuronyl (GlcA) and N-acetyl-D-glucosaminoglycan (GlcNAC) transferase activities [1]. The nature of the defect in heparan sulphate biosynthesis in HME is unclear.

Literature references

  1. Lind T, Tufaro F, McCormick C, Lindahl U, Lidholt K; , J Biol Chem 1998;273:26265-26268.: The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate. PUBMED:9756849 EPMC:9756849


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR040911

In addition to a b-glucuronyltransferase domain, exostosins contain an additional alpha 1,4-N-acetylglucosaminyltransferase domain that belongs to family GT64 [ PUBMED:9756849 , PUBMED:10864928 ]. Activities of both exostosin GT domains are required for synthesizing the backbone of glycosaminoglycan, heparan sulfate. In plants, many genes have been shown to encode proteins with significant sequence similarity to the exostosin b-glucuronyltransferase domain and therefore are grouped into family GT47 [ PUBMED:14659703 ]. This entry represents the GT47 domain of exostosins.

There are five identified human EXT family proteins (EXT1, EXT2, EXTL1, EXTL2 and EXTL3), which are members of the hereditary multiple exostoses family of tumor suppressors [ PUBMED:17237233 ]. They are glycosyltransferases required for the biosynthesis of heparan sulfate. Hereditary multiple exostoses (EXT) is an autosomal dominant disorder that is characterised by the appearance of multiple outgrowths of the long bones (exostoses) at their epiphyses [ PUBMED:9473480 ]. Mutations in two homologous genes, EXT1 and EXT2, are responsible for the EXT syndrome. The human and mouse EXT genes have at least two homologues in the invertebrate Caenorhabditis elegans, indicating that they do not function exclusively as regulators of bone growth. EXT1 and EXT2 have both been shown to encode glycosyltransferases involved in the chain elongation step of heparan sulphate biosynthesis [ PUBMED:9756849 ].

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...

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
(31)
Full
(11658)
Representative proteomes UniProt
(18828)
RP15
(2217)
RP35
(6251)
RP55
(10312)
RP75
(12967)
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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
(31)
Full
(11658)
Representative proteomes UniProt
(18828)
RP15
(2217)
RP35
(6251)
RP55
(10312)
RP75
(12967)
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
(31)
Full
(11658)
Representative proteomes UniProt
(18828)
RP15
(2217)
RP35
(6251)
RP55
(10312)
RP75
(12967)
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: Pfam-B_2031 (release 6.4)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Mifsud W
Number in seed: 31
Number in full: 11658
Average length of the domain: 272.6 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 52.3 %

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 33.4 33.4
Trusted cut-off 33.4 33.4
Noise cut-off 33.3 33.3
Model length: 300
Family (HMM) version: 18
Download: download the raw HMM for this family

Species distribution

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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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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
A0A044R6C8 View 3D Structure Click here
A0A044S9M2 View 3D Structure Click here
A0A044UZ00 View 3D Structure Click here
A0A077YYI2 View 3D Structure Click here
A0A077Z0L8 View 3D Structure Click here
A0A077ZE64 View 3D Structure Click here
A0A096QRE7 View 3D Structure Click here
A0A096U994 View 3D Structure Click here
A0A0G2KAH7 View 3D Structure Click here
A0A0H5S335 View 3D Structure Click here
A0A0K0E0W0 View 3D Structure Click here
A0A0K0EEE8 View 3D Structure Click here
A0A0N4UEX7 View 3D Structure Click here
A0A0N4UGE8 View 3D Structure Click here
A0A0N4UIH7 View 3D Structure Click here
A0A0P0V9G9 View 3D Structure Click here
A0A0P0VLM1 View 3D Structure Click here
A0A0P0W5Z6 View 3D Structure Click here
A0A0P0WT52 View 3D Structure Click here
A0A0P0X7X1 View 3D Structure Click here
A0A0P0Y876 View 3D Structure Click here
A0A0R0ELE4 View 3D Structure Click here
A0A0R0G5N0 View 3D Structure Click here
A0A0R0GQM1 View 3D Structure Click here
A0A0R0HAT7 View 3D Structure Click here
A0A0R0HFK7 View 3D Structure Click here
A0A0R0HJB7 View 3D Structure Click here
A0A0R0HRG1 View 3D Structure Click here
A0A0R0HZ13 View 3D Structure Click here
A0A0R0I559 View 3D Structure Click here
A0A0R0IGJ1 View 3D Structure Click here
A0A0R0IJW3 View 3D Structure Click here
A0A0R0JCY0 View 3D Structure Click here
A0A0R0JHS0 View 3D Structure Click here
A0A0R0JI99 View 3D Structure Click here
A0A0R0JIK3 View 3D Structure Click here
A0A0R0K5U6 View 3D Structure Click here
A0A0R0KLU6 View 3D Structure Click here
A0A0R0KV06 View 3D Structure Click here
A0A0R0LF51 View 3D Structure Click here

trRosetta Structure

The structural model below was generated by the Baker group with the trRosetta software using the Pfam UniProt multiple sequence alignment.

The InterPro website shows the contact map for the Pfam SEED alignment. Hovering or clicking on a contact position will highlight its connection to other residues in the alignment, as well as on the 3D structure.

Improved protein structure prediction using predicted inter-residue orientations. Jianyi Yang, Ivan Anishchenko, Hahnbeom Park, Zhenling Peng, Sergey Ovchinnikov, David Baker Proceedings of the National Academy of Sciences Jan 2020, 117 (3) 1496-1503; DOI: 10.1073/pnas.1914677117;