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1  structure 144  species 0  interactions 561  sequences 65  architectures

Family: FYRC (PF05965)

Summary: F/Y rich C-terminus

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F/Y rich C-terminus Provide feedback

This region is normally found in the trithorax/ALL1 family proteins. It is similar to SM00542.

Literature references

  1. Mbangkollo D, Burnett R, McCabe N, Thirman M, Gill H, Yu H, Rowley JD, Diaz MO; , DNA Cell Biol 1995;14:475-483.: The human MLL gene: nucleotide sequence, homology to the Drosophila trx zinc-finger domain, and alternative splicing. PUBMED:7598802 EPMC:7598802


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003889

The "FY-rich" domain N-terminal (FYRN) and "FY-rich" domain C-terminal (FYRC) sequence motifs are two poorly characterised phenylalanine/ tyrosine-rich regions of around 50 and 100 amino acids, respectively, that are found in a variety of chromatin-associated proteins [PUBMED:9247308, PUBMED:10838566, PUBMED:11779830, PUBMED:20506279]. They are particularly common in histone H3K4 methyltransferases most notably in a family of proteins that includes human mixed lineage leukemia (MLL) and the Drosophila melanogaster protein trithorax. Both of these enzymes play a key role in the epigenetic regulation of gene expression during development, and the gene coding for MLL is frequently rearranged in infant and secondary therapy-related acute leukemias. They are also found in transforming growth factor beta regulator 1 (TBRG1), a growth inhibitory protein induced in cells undergoing arrest in response to DNA damage and transforming growth factor (TGF)-beta1. As TBRG1 has been shown to bind to both the tumor suppressor p14ARF and MDM2, a key regulator of p53, it is also known as nuclear interactor of ARF and MDM2 (NIAM). In most proteins, the FYRN and FYRC regions are closely juxtaposed, however, in MLL and its homologues they are far distant. To be fully active, MLL must be proteolytically processed by taspase1, which cleaves the protein between the FYRN and FYRC regions [PUBMED:12482972]. The N-terminal and C-terminal fragments remain associated after proteolysis apparently as a result of an interaction between the FYRN and FYRC regions. How proteolytic processing regulates the activity of MLL is not known. Intriguingly, the FYRN and FYRC motifs of a second family of histone H3K4 methyltransferases, represented by MLL2 and MLL4 in humans and TRR in Drosophila melanogaster, are closely juxtaposed. FYRN and FYRC motifs are found in association with modules that create or recognise histone modifications in proteins from a wide range of eukaryotes, and it is likely that in these proteins they have a conserved role related to some aspect of chromatin biology [PUBMED:20506279].

The FYRN and FYRC regions are not separate independently folded domains, but are components of a distinct protein module, The FYRN and FYRC motifs both form part of a single folded module (the FYR domain), which adopts an alpha+ beta fold consisting of a six-stranded antiparallel beta-sheet followed by four consecutive alpha-helices. The FYRN region corresponds to beta-strands 1-4 and their connecting loops, whereas the FYRC motif maps to beta-strand 5, beta-strand 6 and helices alpha1 to alpha4. Most of the conserved tyrosine and phenylalanine residues, after which these motifs are named are involved in interactions that stabilise the fold. Proteins such as MLL, in which the FYRN and FYRC regions are separated by hundreds of amino acids, are expected to contain FYR domains with a large insertion between two of the strands of the beta-sheet (strands 4 and 5) [PUBMED:20506279].

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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(48)
Full
(561)
Representative proteomes NCBI
(525)
Meta
(9)
RP15
(122)
RP35
(175)
RP55
(266)
RP75
(363)
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Format an alignment

  Seed
(48)
Full
(561)
Representative proteomes NCBI
(525)
Meta
(9)
RP15
(122)
RP35
(175)
RP55
(266)
RP75
(363)
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
(48)
Full
(561)
Representative proteomes NCBI
(525)
Meta
(9)
RP15
(122)
RP35
(175)
RP55
(266)
RP75
(363)
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:

HMM logo

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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.

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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_1170 (release 8.0)
Previous IDs: none
Type: Family
Author: Yeats C
Number in seed: 48
Number in full: 561
Average length of the domain: 85.00 aa
Average identity of full alignment: 28 %
Average coverage of the sequence by the domain: 4.25 %

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 20.8 20.8
Trusted cut-off 20.9 20.9
Noise cut-off 20.7 20.7
Model length: 86
Family (HMM) version: 9
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 FYRC domain has been found. There are 1 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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