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16  structures 3218  species 0  interactions 14974  sequences 136  architectures

Family: GFA (PF04828)

Summary: Glutathione-dependent formaldehyde-activating enzyme

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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.

Glutathione-dependent formaldehyde-activating enzyme Provide feedback

The GFA enzyme catalyzes the first step in the detoxification of formaldehyde. This domain has a beta-tent fold [1].

Literature references

  1. Lupas AN, Zhu H, Korycinski M;, PLoS Comput Biol. 2015;11:e1004023.: The thalidomide-binding domain of cereblon defines the CULT domain family and is a new member of the beta-tent fold. PUBMED:25569776 EPMC:25569776


This tab holds annotation information from the InterPro database.

InterPro entry IPR006913

Centrome protein (CENP)-V is a kinetochore protein that drives the progression of mitosis by coordinating chromatin condensation, positioning of sister chromatid centromeres and targeting of the chromosome passager complex (CPC), a machinery that regulates the attachment of spindle microtubules (MTs) to kinetochores. CENP-V homologues are found in all vertebrates as well as in plants and nematodes. At the C-terminal end, CENP-V possesses an evolutionally conserved domain that comprises an array of seven cysteines and shows high structural similarity to glutathione-dependent formaldehyde-activating enzyme (Gfa), an enzyme responsible for formaldehyde detoxification in prokaryotes. CENP-V could be an enzyme that scavenges the formaldehyde produced in histone demethylation reactions. The three central cysteines and the flanking four cysteines separately coordinate to zinc, forming a catalytic centre and a structural fold for a tertiary structure, respectively [ PUBMED:18772885 , PUBMED:19930468 , PUBMED:15548539 ].

The main topological feature of the CENP-V/GFA domain is an extremely twisted mixed eight-stranded beta-shee. Within this beta-sheet, the strands beta8, beta9, and beta4 form a sandwich with another triple stranded mixed beta-sheet (beta5, beta2, beta1). The interconnection between the sheets is mediated by four 3(10) helices and two alpha helices. The sandwich arrangement of the beta-strands is further buttressed by a terahedral zinc coordinated by the side chains of four cysteines. It appears that this zinc atom has only a structural role. A second zinc ion stabilizes a large hairpin loop that connects beta3 and beta4 via residues of three cysteines [ PUBMED:15548539 ].

This entry represents the CENP-V/GFA domain.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

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 Beta-tent (CL0080), which has the following description:

This clan contains TCTP, Mss4 and SelR families [1]. The common fold of members of this superfamily has been termed the beta-tent fold [2]. This fold contains two four stranded antiparallel beta sheets. These are oriented at right angles and pinned together at their tip by a zinc ion [2].

The clan contains the following 7 members:

GFA Mss4 NTP_transf_9 RIG-I_C-RD SelR TCTP Yippee-Mis18

Alignments

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 and the UniProtKB 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
(32)
Full
(14974)
Representative proteomes UniProt
(56878)
RP15
(1508)
RP35
(5868)
RP55
(12825)
RP75
(23963)
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PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(32)
Full
(14974)
Representative proteomes UniProt
(56878)
RP15
(1508)
RP35
(5868)
RP55
(12825)
RP75
(23963)
Alignment:
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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
(32)
Full
(14974)
Representative proteomes UniProt
(56878)
RP15
(1508)
RP35
(5868)
RP55
(12825)
RP75
(23963)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

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 View help on the curation process

Seed source: Pfam-B_2779 (release 7.6)
Previous IDs: DUF636;
Type: Domain
Sequence Ontology: SO:0000417
Author: Kerrison ND
Number in seed: 32
Number in full: 14974
Average length of the domain: 91.2 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 55.39 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.3 24.3
Trusted cut-off 24.3 24.3
Noise cut-off 24.2 24.2
Model length: 93
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Selections

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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 GFA domain has been found. There are 16 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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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0A2VMN3 View 3D Structure Click here
A0A0D2DAC3 View 3D Structure Click here
A0A0D2DU69 View 3D Structure Click here
A0A0D2E4J8 View 3D Structure Click here
A0A0D2EJU9 View 3D Structure Click here
A0A0D2FI87 View 3D Structure Click here
A0A0D2G5T2 View 3D Structure Click here
A0A0D2G6L9 View 3D Structure Click here
A0A0D2G8H2 View 3D Structure Click here
A0A0D2G9C5 View 3D Structure Click here
A0A0D2GCP2 View 3D Structure Click here
A0A0D2GRB1 View 3D Structure Click here
A0A0D2GRV2 View 3D Structure Click here
A0A0D2GTT4 View 3D Structure Click here
A0A0D2GZ19 View 3D Structure Click here
A0A0D2H176 View 3D Structure Click here
A0A0D2H3I8 View 3D Structure Click here
A0A0D2HGE7 View 3D Structure Click here
A0A0D2HH03 View 3D Structure Click here
A0A0D2HPD8 View 3D Structure Click here
A0A0H3GMK7 View 3D Structure Click here
A0A0U1RR11 View 3D Structure Click here
A0A0U1RRI6 View 3D Structure Click here
A0A175VWR8 View 3D Structure Click here
A0A175VZ96 View 3D Structure Click here
A0A175W0Y9 View 3D Structure Click here
A0A175W2E8 View 3D Structure Click here
A0A175W8T3 View 3D Structure Click here
A0A175WAX4 View 3D Structure Click here
A0A175WBH7 View 3D Structure Click here
A0A175WCE1 View 3D Structure Click here
A0A175WCU5 View 3D Structure Click here
A0A175WE83 View 3D Structure Click here
A0A175WFC9 View 3D Structure Click here
A0A175WI99 View 3D Structure Click here
A0A175WIF4 View 3D Structure Click here
A0A1C1C9T3 View 3D Structure Click here
A0A1C1CDP2 View 3D Structure Click here
A0A1C1CFN5 View 3D Structure Click here
A0A1C1CG76 View 3D Structure Click here