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72  structures 5508  species 4  interactions 85410  sequences 4295  architectures

Family: GGDEF (PF00990)

Summary: Diguanylate cyclase, GGDEF domain

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GGDEF domain Edit Wikipedia article

GGDEF domain
PDB 1w25 EBI.jpg
response regulator PleD in complex with c-diGMP
Symbol GGDEF
Pfam PF00990
Pfam clan CL0276
InterPro IPR000160
SCOP 1w25
CDD cd01949

In molecular biology, the GGDEF domain is a protein domain which appears to be ubiquitous in bacteria and is often linked to a regulatory domain, such as a phosphorylation receiver or oxygen sensing domain. Its function is to act as a diguanylate cyclase and synthesize cyclic di-GMP, which is used as an intracellular signalling molecule in a wide variety of bacteria.[1][2] Enzymatic activity can be strongly influenced by the adjacent domains. Processes regulated by this domain include exopolysaccharide synthesis, biofilm formation, motility and cell differentiation.

Structural studies of PleD from Caulobacter crescentus show that this domain forms a five-stranded beta sheet surrounded by helices, similar to the catalytic core of adenylate cyclase.[3]


  1. ^ Paul R, Weiser S, Amiot NC, Chan C, Schirmer T, Giese B, Jenal U (March 2004). "Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain". Genes Dev. 18 (6): 715–27. PMC 387245Freely accessible. PMID 15075296. doi:10.1101/gad.289504. 
  2. ^ Ryjenkov DA, Tarutina M, Moskvin OV, Gomelsky M (March 2005). "Cyclic diguanylate is a ubiquitous signaling molecule in bacteria: insights into biochemistry of the GGDEF protein domain". J. Bacteriol. 187 (5): 1792–8. PMC 1064016Freely accessible. PMID 15716451. doi:10.1128/JB.187.5.1792-1798.2005. 
  3. ^ Chan C, Paul R, Samoray D, Amiot NC, Giese B, Jenal U, Schirmer T (December 2004). "Structural basis of activity and allosteric control of diguanylate cyclase". Proc. Natl. Acad. Sci. U.S.A. 101 (49): 17084–9. PMC 535365Freely accessible. PMID 15569936. doi:10.1073/pnas.0406134101. 

This article incorporates text from the public domain Pfam and InterPro IPR000160

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

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.

Diguanylate cyclase, GGDEF domain Provide feedback

This domain is found linked to a wide range of non-homologous domains in a variety of bacteria. It has been shown to be homologous to the adenylyl cyclase catalytic domain [1] and has diguanylate cyclase activity [4]. This observation correlates with the functional information available on two GGDEF-containing proteins, namely diguanylate cyclase and phosphodiesterase A of Acetobacter xylinum, both of which regulate the turnover of cyclic diguanosine monophosphate. In the WspR protein of Pseudomonas aeruginosa, the GGDEF domain acts as a diguanylate cyclase, PDB:3bre when the whole molecule appears to form a tetramer consisting of two symmetrically-related dimers representing a biological unit. The active site is the GGD/EF motif, buried in the structure, and the cyclic dimeric guanosine monophosphate (c-di-GMP) bind to the inhibitory-motif RxxD on the surface. The enzyme thus catalyses the cyclisation of two guanosine triphosphate (GTP) molecules to one c-di-GMP molecule [6,7,8].

Literature references

  1. Pei J, Grishin NV; , Proteins 2001;42:210-216.: GGDEF domain is homologous to adenylyl cyclase. PUBMED:11119645 EPMC:11119645

  2. Galperin MY, Nikolskaya AN, Koonin EV; , FEMS Microbiol Lett 2001;203:11-21.: Novel domains of the prokaryotic two-component signal transduction systems. PUBMED:11557134 EPMC:11557134

  3. Jenal U; , Curr Opin Microbiol 2004;7:185-191.: Cyclic di-guanosine-monophosphate comes of age: a novel secondary messenger involved in modulating cell surface structures in bacteria?. PUBMED:15063857 EPMC:15063857

  4. Paul R, Weiser S, Amiot NC, Chan C, Schirmer T, Giese B, Jenal U; , Genes Dev 2004;18:715-727.: Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain. PUBMED:15075296 EPMC:15075296

  5. Galperin MY; , Environ Microbiol 2004;6:552-567.: Bacterial signal transduction network in a genomic perspective. PUBMED:15142243 EPMC:15142243

  6. Chan C, Paul R, Samoray D, Amiot NC, Giese B, Jenal U, Schirmer T; , Proc Natl Acad Sci U S A 2004;101:17084-17089.: Structural basis of activity and allosteric control of diguanylate cyclase. PUBMED:15569936 EPMC:15569936

  7. Christen B, Christen M, Paul R, Schmid F, Folcher M, Jenoe P, Meuwly M, Jenal U;, J Biol Chem. 2006;281:32015-32024.: Allosteric control of cyclic di-GMP signaling. PUBMED:16923812 EPMC:16923812

  8. De N, Pirruccello M, Krasteva PV, Bae N, Raghavan RV, Sondermann H;, PLoS Biol. 2008;6:e67.: Phosphorylation-independent regulation of the diguanylate cyclase WspR. PUBMED:18366254 EPMC:18366254

  9. Levet-Paulo M, Lazzaroni JC, Gilbert C, Atlan D, Doublet P, Vianney A;, J Biol Chem. 2011;286:31136-31144.: The atypical two-component sensor kinase Lpl0330 from Legionella pneumophila controls the bifunctional diguanylate cyclase-phosphodiesterase Lpl0329 to modulate bis-(3'-5')-cyclic dimeric GMP synthesis. PUBMED:21757706 EPMC:21757706

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000160

The GGDEF domain, which has been named after the conserved central sequence pattern GG[DE][DE]F is widespread in prokaryotes. It is typically present in multidomain proteins containing regulatory domains of signaling pathways or protein-protein or protein-ligand interaction modules, such as the response regulatory domain, the PAS/PAC domain, the HAMP domain, the GAF domain, the FHA domain or the TPR repeat. However a few single-domain proteins are also known. The GGDEF domain is involved in signal transduction and is likely to catalyze synthesis or hydrolysis of cyclic diguanylate (c-diGMP, bis(3',5')-cyclic diguanylic acid), an effector molecule that consists of two cGMP moieties bound head-to-tail [PUBMED:11557134, PUBMED:11682196, PUBMED:11119645].

Structural studies of PleD from Caulobacter crescentus show that this domain forms a five-stranded beta sheet surrounded by helices, similar to the catalytic core of adenylate cyclase [PUBMED:15569936].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Nucleot_cyclase (CL0276), which has the following description:

This superfamily includes adenylyl cyclase and the GGDEF domain [1].

The clan contains the following 7 members:

DUF1053 DUF3692 EAL GCH_III GGDEF GGDEF_2 Guanylate_cyc


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Curation and family details

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Seed source: Pfam-B_112 (release 3.0)
Previous IDs: DUF9;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 45
Number in full: 85410
Average length of the domain: 154.10 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 26.70 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.2 22.2
Trusted cut-off 22.2 22.2
Noise cut-off 22.1 22.1
Model length: 161
Family (HMM) version: 21
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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There are 4 interactions for this family. More...

EAL bZIP_1 GGDEF Response_reg


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 GGDEF domain has been found. There are 72 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 sequence.

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