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2  structures 186  species 0  interactions 1045  sequences 26  architectures

Family: Fringe (PF02434)

Summary: Fringe-like

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Fringe-like Provide feedback

The drosophila protein fringe (FNG) is a glucosaminyltransferase that controls the response of the Notch receptor to specific ligands [2]. FNG is localised to the Golgi apparatus [1] (not secreted as previously thought). Modification of Notch occurs through glycosylation by FNG. The xenopus homologue, lunatic fringe, has been implicated in a variety of functions.

Literature references

  1. Munro S, Freeman M; , Curr Biol 2000;10:813-820.: The Notch signalling regulator Fringe acts in the Golgi apparatus and requires the glycosyltransferase signature motif DXD. PUBMED:10899003 EPMC:10899003

  2. Munro S, Freeman M; , Curr Biol 2000;10:813-820.: The Notch signalling regulator Fringe acts in the Golgi apparatus and requires the glycosyltransferase signature motif DXD. PUBMED:10899003 EPMC:10899003


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003378

The Notch receptor is a large, cell surface transmembrane protein involved in a wide variety of developmental processes in higher organisms [PUBMED:10221902]. It becomes activated when its extracellular region binds to ligands located on adjacent cells. Much of this extracellular region is composed of EGF-like repeats, many of which can be O-fucosylated. A number of these O-fucosylated repeats can in turn be further modified by the action of a beta-1,3-N-acetylglucosaminyltransferase enzyme known as Fringe [PUBMED:12417415]. Fringe potentiates the activation of Notch by Delta ligands, while inhibiting activation by Serrate/Jagged ligands. This regulation of Notch signalling by Fringe is important in many processes [PUBMED:14570055].

Four distinct Fringe proteins have so far been studied in detail; Drosophila Fringe (Dfng) and its three mammalian homologues Lunatic Fringe (Lfng), Radical Fringe (Rfng) and Manic Fringe (Mfng). Dfng, Lfng and Rfng have all been shown to play important roles in developmental processes within their host, though the phenotype of mutants can vary between species e.g. Rfng mutants are retarded in wing development in chickens, but have no obvious phenotype in mice [PUBMED:7954826, PUBMED:12001066, PUBMED:9121551]. Mfng mutants have not, so far, been charcterised. Biochemical studies indicate that the Fringe proteins are fucose-specific transferases requiring manganese for activity and utilising UDP-N-acetylglucosamine as a donor substrate [PUBMED:16221665]. The three mammalian proteins show distinct variations in their catalytic efficiencies with different substrates.

Dfng is a glucosaminyltransferase that controls the response of the Notch receptor to specific ligands which is localised to the Golgi apparatus [PUBMED:10899003] (not secreted as previously thought). Modification of Notch occurs through glycosylation by Dfng.

This entry consists of Fringe proteins and related glycosyltransferase enzymes including:

  • Beta-1,3-glucosyltransferase, which glucosylates O-linked fucosylglycan on thrombospondin type 1 repeat domains [PUBMED:16899492].
  • Core 1 beta1,3-galactosyltransferase 1, generates the core T antigen, which is a precursor for many extended O-glycans in glycoproteins and plays a central role in many processes, such as angiogenesis, thrombopoiesis and kidney homeostasis development [PUBMED:11673471].

Gene Ontology

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Domain organisation

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Alignments

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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.

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(27)
Full
(1045)
Representative proteomes NCBI
(1675)
Meta
(8)
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(208)
RP35
(292)
RP55
(533)
RP75
(715)
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  Seed
(27)
Full
(1045)
Representative proteomes NCBI
(1675)
Meta
(8)
RP15
(208)
RP35
(292)
RP55
(533)
RP75
(715)
Alignment:
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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
(27)
Full
(1045)
Representative proteomes NCBI
(1675)
Meta
(8)
RP15
(208)
RP35
(292)
RP55
(533)
RP75
(715)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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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.

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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_1900 (release 5.4)
Previous IDs: none
Type: Family
Author: Mian N, Bateman A
Number in seed: 27
Number in full: 1045
Average length of the domain: 183.50 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 50.40 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.5 20.5
Trusted cut-off 20.5 20.5
Noise cut-off 20.4 20.4
Model length: 252
Family (HMM) version: 11
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 Fringe domain has been found. There are 2 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 seqence.

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