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61  structures 3371  species 0  interactions 6829  sequences 61  architectures

Family: Fic (PF02661)

Summary: Fic/DOC family

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This is the Wikipedia entry entitled "Fic/DOC protein family". More...

Fic/DOC protein family Edit Wikipedia article

Fic/DOC family
PDB 2f6s EBI.jpg
structure of cell filamentation protein (fic) from helicobacter pylori
Identifiers
Symbol Fic
Pfam PF02661
InterPro IPR003812

In molecular biology, the Fic/DOC protein family is a family of proteins which includes the Fic (filamentation induced by cAMP) protein and doc (death on curing) protein. The Fic protein is involved in cell division and is suggested to be involved in the synthesis of p-aminobenzoate or folate, indicating that the Fic protein and cAMP are involved in a regulatory mechanism of cell division via folate metabolism.[1] This family contains a central conserved motif HPFXXGNG in most members. The exact molecular function of these proteins is uncertain. P1 lysogens of Escherichia coli carry the prophage as a stable low copy number plasmid. The frequency with which viable cells cured of prophage are produced is about 10(-5) per cell per generation.[1] A significant part of this remarkable stability can be attributed to a plasmid-encoded mechanism that causes death of cells that have lost P1.[2] In other words, the lysogenic cells appear to be addicted to the presence of the prophage. The plasmid withdrawal response depends on a gene named doc (death on curing) that is represented by this family.

References

  1. ^ a b Komano T, Utsumi R, Kawamukai M (1991). "Functional analysis of the fic gene involved in regulation of cell division". Res. Microbiol. 142 (2-3): 269–77. doi:10.1016/0923-2508(91)90040-h. PMID 1656497. 
  2. ^ Lehnherr H, Maguin E, Jafri S, Yarmolinsky MB (October 1993). "Plasmid addiction genes of bacteriophage P1: doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained". J. Mol. Biol. 233 (3): 414–28. doi:10.1006/jmbi.1993.1521. PMID 8411153. 

This article incorporates text from the public domain Pfam and InterPro IPR003812

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Fic/DOC family Provide feedback

This family consists of the Fic (filamentation induced by cAMP) protein and doc (death on curing). The Fic protein is involved in cell division and is suggested to be involved in the synthesis of PAB or folate, indicating that the Fic protein and cAMP are involved in a regulatory mechanism of cell division via folate metabolism [1]. This family contains a central conserved motif HPFXXGNG in most members. The exact molecular function of these proteins is uncertain. P1 lysogens of Escherichia coli carry the prophage as a stable low copy number plasmid. The frequency with which viable cells cured of prophage are produced is about 10(-5) per cell per generation [1]. A significant part of this remarkable stability can be attributed to a plasmid-encoded mechanism that causes death of cells that have lost P1 [2]. In other words, the lysogenic cells appear to be addicted to the presence of the prophage. The plasmid withdrawal response depends on a gene named doc (death on curing) that is represented by this family [2]. Doc induces a reversible growth arrest of E. coli cells by targetting the protein synthesis machinery. Doc hosts the C-terminal domain of its antitoxin partner Phd (prevents host death) through fold complementation, a domain that is intrinsically disordered in solution but that folds into an alpha-helix on binding to Doc [3].This domain forms complexes with Phd antitoxins containing PF02604.

Literature references

  1. Komano T, Utsumi R, Kawamukai M; , Res Microbiol 1991;142:269-277.: Functional analysis of the fic gene involved in regulation of cell division. PUBMED:1656497 EPMC:1656497

  2. Lehnherr H, Maguin E, Jafri S, Yarmolinsky MB; , J Mol Biol 1993;233:414-428.: Plasmid addiction genes of bacteriophage P1: doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained. PUBMED:8411153 EPMC:8411153

  3. Garcia-Pino A, Christensen-Dalsgaard M, Wyns L, Yarmolinsky M, Magnuson RD, Gerdes K, Loris R; , J Biol Chem 2008; [Epub ahead of print]: Doc of prophage P1 is inhibited by its antitoxin partner Phd though fold complementation. PUBMED:18757857 EPMC:18757857


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003812

This globular domain is named fido after the Fic and Doc proteins where is found. It is approximately 125 to 150 residues long, and is present in proteins from all kingdoms of life [PUBMED:14659018, PUBMED:18757857, PUBMED:19127588, PUBMED:19503829], including:

  • Fic (filamentation induced by cAMP) from diverse bacteria. It contains a longer insert in the fido domain.
  • Doc (death on curing) proteins from phage P1 and several bacteria. All these proteins contain a minimal stand-alone version of the fido domain.
  • HypE (Huntingtin associated protein E) from animal. In humans, HypE is thought to interact with Huntingtin, one of the major proteins in the Huntington's disease protein interaction network. Proteins related to HypE are also found in several bacteria and some archaea. HypE proteins contain a longer insert in their fido domain and are typically multidomain proteins.
  • Type IV secretion system effector AnkX from Legionella.
  • VopS, a type III secretion system effector from Vibrio that causes eukaryotic cell cytotoxicity.
  • IbpA (virulence factor p76) from Haemophilus somnus. It includes an N- terminal haemagglutination activity domain, two fido domains and a peptidase C58 domain.
  • BepA, an anti-apoptotic bacterial effector protein, which is a type IV secretion system substrate.

The fido domain of Vibrio VopS covalently modifies Rho GTPase threonine with AMP to inhibit downstream signaling events in host cells. The AMPylation activity extends to a eukaryotic fido domain in Drosophila fic homologue CG9523. AMPylation represents a newly discovered posttranslational modification used to stably modify proteins with AMP. This signaling mechanism is predicted to be functionally similar to other posttranslation modifications such as phosphorylation, SUMOylation or acetylation, because the added moiety changes the activity of the modified protein. The covalent attachment of AMP by a phosphodiester bond is predicted to be reversible and is bulky enough to provide a docking site for a putative AMP binding domain [PUBMED:19503829].

The fido domain contains a central motif conserved in most sequences (H-x-F-x-[DE]-[AG]-N-[GK]-R), with the motif His contributing to fic AMPylation. The fido domain adopts an alpha-helical fold, arranged as a six-helix up and down bundle [PUBMED:18757857, PUBMED:19127588, PUBMED:19503829].

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
(221)
Full
(6829)
Representative proteomes NCBI
(5456)
Meta
(731)
RP15
(529)
RP35
(1058)
RP55
(1363)
RP75
(1631)
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  Seed
(221)
Full
(6829)
Representative proteomes NCBI
(5456)
Meta
(731)
RP15
(529)
RP35
(1058)
RP55
(1363)
RP75
(1631)
Alignment:
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  Seed
(221)
Full
(6829)
Representative proteomes NCBI
(5456)
Meta
(731)
RP15
(529)
RP35
(1058)
RP55
(1363)
RP75
(1631)
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.

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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: COG2184 & COG3654
Previous IDs: none
Type: Family
Author: Bashton M, Bateman A
Number in seed: 221
Number in full: 6829
Average length of the domain: 97.70 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 34.91 %

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 21.7 21.7
Trusted cut-off 21.7 21.7
Noise cut-off 21.6 21.6
Model length: 97
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 Fic domain has been found. There are 61 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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