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10  structures 3379  species 1  interaction 3565  sequences 24  architectures

Family: Sdh5 (PF03937)

Summary: Flavinator of succinate dehydrogenase

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Flavinator of succinate dehydrogenase Provide feedback

This family includes the highly conserved mitochondrial and bacterial proteins Sdh5/SDHAF2/SdhE. Both yeast and human Sdh5/SDHAF2 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Mutational inactivation of Sdh5 confers tumor susceptibility in humans [1]. Bacterial homologues of Sdh5, termed SdhE, are functionally conserved being required for the flavinylation of SdhA and succinate dehydrogenase activity. Like Sdh5, SdhE interacts with SdhA. Furthermore, SdhE was characterised as a FAD co-factor chaperone that directly binds FAD to facilitate the flavinylation of SdhA. Phylogenetic analysis demonstrates that SdhE/Sdh5 proteins evolved only once in an ancestral alpha-proteobacteria prior to the evolution of the mitochondria and now remain in subsequent descendants including eukaryotic mitochondria and the alpha, beta and gamma proteobacteria [2]. This family was previously annotated in Pfam as being a divergent TPR repeat but structural evidence has indicated this is not true. The E. coli protein, YgfY also acts as the antitoxin to the membrane-bound toxin family Cpta, PF13166 whose E. coli member YgfX, expressed from the same operon as YgfY [3].

Literature references

  1. Hao HX, Khalimonchuk O, Schraders M, Dephoure N, Bayley JP, Kunst H, Devilee P, Cremers CW, Schiffman JD, Bentz BG, Gygi SP, Winge DR, Kremer H, Rutter J;, Science. 2009;325:1139-1142.: SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. PUBMED:19628817 EPMC:19628817

  2. McNeil MB, Clulow JS, Wilf NM, Salmond GP, Fineran PC;, J. Biol. Chem. 2012;0:0-0.: SdhE is a conserved protein required for the flavinylation of succinate dehydrogenase in bacteria. PUBMED:22474332 EPMC:22474332

  3. Masuda H, Tan Q, Awano N, Yamaguchi Y, Inouye M;, FEMS Microbiol Lett. 2012;328:174-181.: A novel membrane-bound toxin for cell division, CptA (YgfX), inhibits polymerization of cytoskeleton proteins, FtsZ and MreB, in Escherichia coli. PUBMED:22239607 EPMC:22239607

  4. McNeil MB, Fineran PC;, Biochim Biophys Acta. 2012; [Epub ahead of print]: Prokaryotic assembly factors for the attachment of flavin to complex II. PUBMED:22985599 EPMC:22985599


This tab holds annotation information from the InterPro database.

InterPro entry IPR005631

This family includes the highly conserved mitochondrial and bacterial proteins Sdh5/SDHAF2/SdhE.

Both yeast and human Sdh5/SDHAF2 interact with the catalytic subunit of the succinate dehydrogenase (SDH) complex, a component of both the electron transport chain and the tricarboxylic acid cycle. Sdh5 is required for SDH-dependent respiration and for Sdh1 flavination (incorporation of the flavin adenine dinucleotide cofactor). Mutational inactivation of Sdh5 confers tumor susceptibility in humans [PUBMED:19628817].

Bacterial homologues of Sdh5, termed SdhE, are functionally conserved being required for the flavinylation of SdhA and succinate dehydrogenase activity. Like Sdh5, SdhE interacts with SdhA. Furthermore, SdhE was characterised as a FAD co-factor chaperone that directly binds FAD to facilitate the flavinylation of SdhA. Phylogenetic analysis demonstrates that SdhE/Sdh5 proteins evolved only once in an ancestral alpha-proteobacteria prior to the evolution of the mitochondria and now remain in subsequent descendants including eukaryotic mitochondria and the alpha, beta and gamma proteobacteria [PUBMED:22474332].

This family was previously annotated in Pfam as being a divergent TPR repeat but structural evidence has indicated this is not true.

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
(292)
Full
(3565)
Representative proteomes UniProt
(9237)
NCBI
(8827)
Meta
(1046)
RP15
(782)
RP35
(2079)
RP55
(3347)
RP75
(4934)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(292)
Full
(3565)
Representative proteomes UniProt
(9237)
NCBI
(8827)
Meta
(1046)
RP15
(782)
RP35
(2079)
RP55
(3347)
RP75
(4934)
Alignment:
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Order:
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
(292)
Full
(3565)
Representative proteomes UniProt
(9237)
NCBI
(8827)
Meta
(1046)
RP15
(782)
RP35
(2079)
RP55
(3347)
RP75
(4934)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

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: COG2938
Previous IDs: DUF339; TPR_div1;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Yeats C , McNeil M , Eberhardt R
Number in seed: 292
Number in full: 3565
Average length of the domain: 71.30 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 56.52 %

HMM information View help on HMM parameters

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 20.9 20.9
Trusted cut-off 21.0 20.9
Noise cut-off 20.8 20.7
Model length: 73
Family (HMM) version: 16
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

Sdh5

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 Sdh5 domain has been found. There are 10 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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