FYRN "FY-rich" domain, N-terminal region
SMART ACC:	SM000541
Description:	is sometimes closely juxtaposed with the C-terminal region (FYRC), but sometimes is far distant. Unknown function, but occurs frequently in chromatin-associated proteins.
InterPro ACC:	IPR003888
InterPro abstract:	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 expand 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 α+β fold consisting of a six-stranded antiparallel β-sheet followed by four consecutive α-helices. The FYRN region corresponds to β-strands 1-4 and their connecting loops, whereas the FYRC motif maps to β-strand 5, β-strand 6 and helices α1 to α4. 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 β-sheet (strands 4 and 5) [ PUBMED:20506279 ]. collapse
GO component:	nucleus (GO:0005634)
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 3 181 FYRN domains in 3 175 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing FYRN domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing FYRN domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Predicted cellular role

Cellular role:	Transport

Relevant references for this domain

Primary literature for the FYRN domain is listed below. Automatically-derived, secondary literature is also available.

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a FYRN domain which could be assigned to a KEGG orthologous group, and not all proteins containing FYRN domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

Some of these pathways are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

KEGG orthologous groups

Some of these KOs are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

3D structures in PDB containing this domain

Links to other resources describing this domain

InterPro	IPR003888