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37  structures 6521  species 0  interactions 37238  sequences 5068  architectures

Family: GAF_2 (PF13185)

Summary: GAF domain

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GAF domain Edit Wikipedia article

GAF domain
PDB 1mc0 EBI.jpg
3',5'-Cyclic Nucleotide Phosphodiesterase 2A, Containing the GAF A and GAF B Domains.[1]
Symbol GAF
Pfam PF01590
Pfam clan CL0161
InterPro IPR003018
SCOP 1fl4

The GAF domain is a type of protein domain that is found in a wide range of proteins from all species.[2] The GAF domain is named after some of the proteins it is found in: cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA. The first structure of a GAF domain solved by Ho and colleagues showed that this domain shared a similar fold with the PAS domain.[3] In mammals, GAF domains are found in five members of the cyclic nucleotide phosphodiesterase superfamily: PDE2, PDE5, and PDE6 which bind cGMP to the GAF domain, PDE10 which binds cAMP, and PDE11 which binds both cGMP and cAMP.[4][5]


Human proteins containing this domain include:


  1. ^ Martinez SE, Wu AY, Glavas NA, Tang XB, Turley S, Hol WG, Beavo JA (October 2002). "The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding". Proceedings of the National Academy of Sciences of the United States of America. 99 (20): 13260–5. Bibcode:2002PNAS...9913260M. doi:10.1073/pnas.192374899. JSTOR 3073384. PMC 130621Freely accessible. PMID 12271124. 
  2. ^ Aravind L, Ponting CP (December 1997). "The GAF domain: an evolutionary link between diverse phototransducing proteins". Trends in Biochemical Sciences. 22 (12): 458–9. doi:10.1016/S0968-0004(97)01148-1. PMID 9433123. 
  3. ^ Ho YS, Burden LM, Hurley JH (October 2000). "Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor". The EMBO Journal. 19 (20): 5288–99. doi:10.1093/emboj/19.20.5288. PMC 314001Freely accessible. PMID 11032796. 
  4. ^ Fawcett L, Baxendale R, Stacey P, McGrouther C, Harrow I, Soderling S, Hetman J, Beavo JA, Phillips SC (March 2000). "Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3702–7. Bibcode:2000PNAS...97.3702F. doi:10.1073/pnas.050585197. JSTOR 121956. PMC 16303Freely accessible. PMID 10725373. 
  5. ^ Schultz JE (2009). "Structural and biochemical aspects of tandem GAF domains". Handbook of Experimental Pharmacology. Handbook of Experimental Pharmacology. 191 (191): 93–109. doi:10.1007/978-3-540-68964-5_6. ISBN 978-3-540-68960-7. PMID 19089327. 

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Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003018

The GAF domain is named after some of the proteins it is found in, including cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA. It is also found in and guanylyl cyclases and phytochromes [ PUBMED:9433123 , PUBMED:20004158 ]. The structure of a GAF domain shows that the domain shares a similar fold with the PAS domain [ PUBMED:11032796 ]. Adenylyl and guanylyl cyclases catalyse ATP and GTP to the second messengers cAMP and cGMP respectively, these products up-regulating catalytic activity by binding to the regulatory GAF domain(s). The opposite hydrolysis reaction is catalysed by phosphodiesterase. cGMP-dependent 3',5'-cyclic phosphodiesterase catalyses the conversion of guanosine 3',5'-cyclic phosphate to guanosine 5'-phosphate. Here too, cGMP regulates catalytic activity by GAF-domain binding. Phytochromes are regulatory photoreceptors in plants and bacteria which exist in two thermally stable states that are reversibly inter-convertible by light, the Pr state absorbs maximally in the red region of the spectrum, while the Pfr state absorbs maximally in the far-red region [ PUBMED:20298248 ].

The GAF domain is also found in FhlA (formate hydrogen lyase transcriptional activator) and NifA, a transcriptional activator required for activation of most Nif operons, which are directly involved in nitrogen fixation. NifA interacts with sigma-54 [ PUBMED:1404379 ].

Gene Ontology

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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 GAF (CL0161), which has the following description:

A clan of related transcriptional regulator domains.

The clan contains the following 14 members:

Autoind_bind bHLH-MYC_N CCB2_CCB4 CodY DUF3369 DUF484 GAF GAF_2 GAF_3 Haem_degrading HrcA IclR PHY SpoVT_C


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Curation and family details

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Curation View help on the curation process

Seed source: Jackhmmer:O27394
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 210
Number in full: 37238
Average length of the domain: 141.30 aa
Average identity of full alignment: 15 %
Average coverage of the sequence by the domain: 22.25 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 28.6 28.6
Trusted cut-off 28.6 28.6
Noise cut-off 28.5 28.5
Model length: 138
Family (HMM) version: 8
Download: download the raw HMM for this family

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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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 GAF_2 domain has been found. There are 37 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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