FH FORKHEAD
SMART ACC:	SM000339
Description:	FORKHEAD, also known as a "winged helix"
InterPro ACC:	IPR001766
InterPro abstract:	The fork head domain is a conserved DNA-binding domain (also known as a "winged helix") of about 100 amino-acid residues. Drosophila melanogaster fork head protein is a transcription factor that promotes terminal rather than segmental development, contains neither homeodomains nor zinc-fingers characteristic of other transcription factors [ PUBMED:2566386 … expand The fork head domain is a conserved DNA-binding domain (also known as a "winged helix") of about 100 amino-acid residues. Drosophila melanogaster fork head protein is a transcription factor that promotes terminal rather than segmental development, contains neither homeodomains nor zinc-fingers characteristic of other transcription factors [ PUBMED:2566386 ]. Instead, it contains a distinct type of DNA-binding region, containing around 100 amino acids, which has since been identified in a number of transcription factors (including D. melanogaster FD1-5, mammalian HNF-3, human HTLF, Saccharomyces cerevisiae HCM1, etc.). This is referred to as the fork head domain but is also known as a 'winged helix' [ PUBMED:2566386 PUBMED:8332212 PUBMED:1356269 ]. The fork head domain binds B-DNA as a monomer [ PUBMED:8332212 ], but shows no similarity to previously identified DNA-binding motifs. Although the domain is found in several different transcription factors, a common function is their involvement in early developmental decisions of cell fates during embryogenesis [ PUBMED:1356269 ]. collapse
GO process:	regulation of DNA-templated transcription (GO:0006355)
GO function:	sequence-specific DNA binding (GO:0043565), DNA-binding transcription factor activity (GO:0003700)
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 22 315 FH domains in 22 242 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing FH domains

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

Predicted cellular role

Binding / catalysis:	DNA-BINDING

Relevant references for this domain

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

Disease genes where sequence variants are found in this domain

UniRef sequences and OMIM curated human diseases associated with missense mutations within the FH domain.

Protein	Description	Disease / phenotype
FOXC1_HUMAN		OMIM:601090 : Iridogoniodysgenesis
FOXC1_HUMAN		OMIM:601631 : Anterior segment mesenchymal dysgenesis ; Rieger anomaly ; Axenfeld anomaly ; Iris hypoplasia and glaucoma
FOXE1_HUMAN		OMIM:602617 : Bamforth-Lazarus syndrome
FOXE1_HUMAN		OMIM:241850 : no description
FOXN1_HUMAN		OMIM:600838 : T-cell immunodeficiency, congenital alopecia, and nail dystrophy

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 FH domain which could be assigned to a KEGG orthologous group, and not all proteins containing FH 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

Pfam	Fork_head
PROSITE	FORK_HEAD_3
InterPro	IPR001766