Summary: GAF domain
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GAF domain Edit Wikipedia article
GAF domain | |||||||||
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![]() 3',5'-Cyclic Nucleotide Phosphodiesterase 2A, Containing the GAF A and GAF B Domains.[1]
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Identifiers | |||||||||
Symbol | GAF | ||||||||
Pfam | PF01590 | ||||||||
Pfam clan | CL0161 | ||||||||
InterPro | IPR003018 | ||||||||
SMART | GAF | ||||||||
SCOP | 1fl4 | ||||||||
SUPERFAMILY | 1fl4 | ||||||||
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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]
Examples
Human proteins containing this domain include:
References
- ^ 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 130621
. PMID 12271124.
- ^ 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.
- ^ 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 314001
. PMID 11032796.
- ^ 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 16303
. PMID 10725373.
- ^ 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
SCOOP: | Autoind_bind bHLH-MYC_N CCB2_CCB4 DUF3369 DUF484 GAF GAF_3 Haem_degrading IclR PAS_4 SpoVT_C |
Similarity to PfamA using HHSearch: | GAF CCB2_CCB4 GAF_3 |
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
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Molecular function | protein binding (GO:0005515) |
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_CAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
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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 (218) |
Full (32598) |
Representative proteomes | UniProt (138340) |
NCBI (277397) |
Meta (1830) |
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RP15 (3784) |
RP35 (14151) |
RP55 (32957) |
RP75 (56896) |
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Jalview | |||||||||
HTML | |||||||||
PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
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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 (218) |
Full (32598) |
Representative proteomes | UniProt (138340) |
NCBI (277397) |
Meta (1830) |
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---|---|---|---|---|---|---|---|---|---|
RP15 (3784) |
RP35 (14151) |
RP55 (32957) |
RP75 (56896) |
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Raw Stockholm | |||||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
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.
Note: You can also download the data file for the tree.
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
Seed source: | Jackhmmer:O27394 |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Bateman A |
Number in seed: | 218 |
Number in full: | 32598 |
Average length of the domain: | 141.30 aa |
Average identity of full alignment: | 16 % |
Average coverage of the sequence by the domain: | 22.11 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 138 | ||||||||||||
Family (HMM) version: | 7 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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Interactions
There is 1 interaction for this family. More...
GAF_2Structures
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 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 sequence.
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