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35  structures 545  species 0  interactions 4445  sequences 32  architectures

Family: Fork_head (PF00250)

Summary: Fork head domain

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Fork head domain Edit Wikipedia article

Fork head domain
PDB 2hfh EBI.jpg
Structure of the winged helix protein Genesis.[1]
Identifiers
Symbol Fork_head
Pfam PF00250
InterPro IPR001766
SMART SM00339
PROSITE PDOC00564
SCOP 2hfh
SUPERFAMILY 2hfh

The fork head domain is a type of protein domain which is often found in transcription factors and whose purpose is to bind DNA.[2]

Function[edit]

The fork head protein of Drosophila melanogaster, a transcription factor that promotes terminal rather than segmental development, contains neither homeodomains nor zinc-fingers characteristic of other transcription factors.[3] 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 HNF3, human HTLF, Saccharomyces cerevisiae HCM1, etc.). This is referred to as the fork head domain but is also known as a "winged helix".[3][4][5] The fork head domain binds B-DNA as a monomer,[4] 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.[5] Members of the class O of forkhead box transcription factors (FoxO) have important roles in metabolism, cellular proliferation, stress tolerance and probably lifespan.[6]

See also[edit]

References[edit]

  1. ^ Marsden I, Jin C, Liao X (May 1998). "Structural changes in the region directly adjacent to the DNA-binding helix highlight a possible mechanism to explain the observed changes in the sequence-specific binding of winged helix proteins". J. Mol. Biol. 278 (2): 293–9. doi:10.1006/jmbi.1998.1703. PMID 9571051. 
  2. ^ Kaufmann E, Knöchel W (June 1996). "Five years on the wings of fork head". Mech. Dev. 57 (1): 3–20. doi:10.1016/0925-4773(96)00539-4. PMID 8817449. 
  3. ^ a b Weigel D, Jürgens G, Küttner F, Seifert E, Jäckle H (May 1989). "The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo". Cell 57 (4): 645–58. doi:10.1016/0092-8674(89)90133-5. PMID 2566386. 
  4. ^ a b Clark KL, Halay ED, Lai E, Burley SK (July 1993). "Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5". Nature 364 (6436): 412–20. doi:10.1038/364412a0. PMID 8332212. 
  5. ^ a b Häcker U, Grossniklaus U, Gehring WJ, Jäckle H (September 1992). "Developmentally regulated Drosophila gene family encoding the fork head domain". Proc. Natl. Acad. Sci. U.S.A. 89 (18): 8754–8. doi:10.1073/pnas.89.18.8754. PMC 49999. PMID 1356269. 
  6. ^ van der Horst A, Burgering BM (June 2007). "Stressing the role of FoxO proteins in lifespan and disease". Nature Reviews Molecular Cell Biology 8 (6): 440–50. doi:10.1038/nrm2190. PMID 17522590. 

This article incorporates text from the public domain Pfam and InterPro IPR001766

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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Literature references

  1. Clark KL, Halay ED, Lai E, Burley SK; , Nature 1993;364:412-420.: Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. PUBMED:8332212 EPMC:8332212


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001766

The fork head protein of Drosophila melanogaster, 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].

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.

  Seed
(21)
Full
(4445)
Representative proteomes NCBI
(4173)
Meta
(4)
RP15
(603)
RP35
(883)
RP55
(1588)
RP75
(2306)
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Format an alignment

  Seed
(21)
Full
(4445)
Representative proteomes NCBI
(4173)
Meta
(4)
RP15
(603)
RP35
(883)
RP55
(1588)
RP75
(2306)
Alignment:
Format:
Order:
Sequence:
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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
(21)
Full
(4445)
Representative proteomes NCBI
(4173)
Meta
(4)
RP15
(603)
RP35
(883)
RP55
(1588)
RP75
(2306)
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: Prosite
Previous IDs: FKH;
Type: Domain
Author: Finn RD
Number in seed: 21
Number in full: 4445
Average length of the domain: 92.50 aa
Average identity of full alignment: 42 %
Average coverage of the sequence by the domain: 20.59 %

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 20.7 20.7
Trusted cut-off 20.7 21.0
Noise cut-off 20.5 20.6
Model length: 96
Family (HMM) version: 13
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 Fork_head domain has been found. There are 35 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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