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6  structures 1889  species 1  interaction 1961  sequences 9  architectures

Family: Sdh5 (PF03937)

Summary: Flavinator of succinate dehydrogenase

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Succinate dehydrogenase complex subunit C". More...

Succinate dehydrogenase complex subunit C Edit Wikipedia article

Succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa

PDB rendering based on 1zp0.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SDHC; CYB560; CYBL; PGL3; QPS1; SDH3
External IDs OMIM602413 MGI1913302 HomoloGene2256 GeneCards: SDHC Gene
Orthologs
Species Human Mouse
Entrez 6391 66052
Ensembl ENSG00000143252 ENSMUSG00000058076
UniProt Q99643 Q9CZB0
RefSeq (mRNA) NM_001035511 NM_025321
RefSeq (protein) NP_001030588 NP_079597
Location (UCSC) Chr 1:
161.28 – 161.33 Mb
Chr 1:
171.13 – 171.15 Mb
PubMed search [1] [2]

Succinate dehydrogenase complex subunit C, also known as succinate dehydrogenase cytochrome b560 subunit, mitochondrial, is a protein that in humans is encoded by the SDHC gene.[1][2]

Gene[edit]

The gene that codes for the SDHC protein is nuclear, even though the protein is located in the inner membrane of the mitochondria. The location of the gene in humans is on the first chromosome at q21. The gene is partitioned in 6 exons. The expressed protein has 170 amino acids.

Function[edit]

SuccDeh.svg

The SDHC protein is one of four nuclear-encoded subunits that comprise succinate dehydrogenase, also known as the mitochondrial complex II, a key enzyme complex of the citric acid cycle and aerobic respiratory chains of mitochondria. The encoded protein is one of two integral membrane proteins that anchor other subunits of the complex, which form the catalytic core, to the inner mitochondrial membrane.[1]

The succinate dehydrogenase (SDH) protein complex catalyzes the oxidation of succinate (succinate + ubiquinone => fumarate + ubiquinol). The SDHA subunit is connected to the SDHB subunit on the hydrophilic, catalytic end of the complex. Electrons removed from succinate transfer SDHA to SDHB and further to the SDHC/SDHD subunits on the hydrophobic end of the complex anchored in the mitochondrial membrane.

The SDH complex is located on the inner membrane of the mitochondria and participates in both the Citric Acid Cycle and Respiratory chain.

SDHC acts as an intermediate in the basic SDH enzyme action:

  1. SDHA converts succinate to fumarate as part of the Citric Acid Cycle. This reaction also converts FAD to FADH2.
  2. Electrons from the FADH2 are transferred to the SDHB subunit iron clusters [2Fe-2S],[4Fe-4S],[3Fe-4S]. This function is part of the Respiratory chain
  3. Finally the electrons are transferred to the Ubiquinone (Q) pool via the SDHC/SDHD subunits.

Clinical significance[edit]

Mutations in this gene have been associated with paragangliomas.[1][3]

Interactive pathway map[edit]

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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TCACycle_WP78 go to article go to article go to article go to article go to HMDB go to article go to article go to article Go to article go to article go to article go to article go to article go to article Go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to HMDB go to article go to article go to article go to article go to article go to article go to article go to article go to article go to article go to WikiPathways go to article go to article go to article go to article
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TCA Cycle edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78". 

References[edit]

  1. ^ a b c "Entrez Gene: succinate dehydrogenase complex". 
  2. ^ Hirawake H, Taniwaki M, Tamura A, Kojima S, Kita K (1997). "Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23". Cytogenet. Cell Genet. 79 (1-2): 132–8. doi:10.1159/000134700. PMID 9533030. 
  3. ^ Niemann S, Müller U, Engelhardt D, Lohse P (July 2003). "Autosomal dominant malignant and catecholamine-producing paraganglioma caused by a splice donor site mutation in SDHC". Hum. Genet. 113 (1): 92–4. doi:10.1007/s00439-003-0938-0. PMID 12658451. 

Further reading[edit]

  • Bayley JP, Weiss MM, Grimbergen A, et al. (2009). "Molecular characterization of novel germline deletions affecting SDHD and SDHC in pheochromocytoma and paraganglioma patients.". Endocr. Relat. Cancer 16 (3): 929–37. doi:10.1677/ERC-09-0084. PMID 19546167. 
  • Pasini B, McWhinney SR, Bei T, et al. (2008). "Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD.". Eur. J. Hum. Genet. 16 (1): 79–88. doi:10.1038/sj.ejhg.5201904. PMID 17667967. 
  • Gaal J, Burnichon N, Korpershoek E, et al. (2010). "Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas.". J. Clin. Endocrinol. Metab. 95 (3): 1274–8. doi:10.1210/jc.2009-2170. PMID 19915015. 
  • Milosevic D, Lundquist P, Cradic K, et al. (2010). "Development and validation of a comprehensive mutation and deletion detection assay for SDHB, SDHC, and SDHD.". Clin. Biochem. 43 (7-8): 700–4. doi:10.1016/j.clinbiochem.2010.01.016. PMID 20153743. 
  • Bonache S, Martí­nez J, Fernández M, et al. (2007). "Single nucleotide polymorphisms in succinate dehydrogenase subunits and citrate synthase genes: association results for impaired spermatogenesis.". Int. J. Androl. 30 (3): 144–52. doi:10.1111/j.1365-2605.2006.00730.x. PMID 17298551. 
  • Cascán A, Lápez-Jiménez E, Landa I, et al. (2009). "Rationalization of genetic testing in patients with apparently sporadic pheochromocytoma/paraganglioma.". Horm. Metab. Res. 41 (9): 672–5. doi:10.1055/s-0029-1202814. PMID 19343621. 
  • Goto Y, Ando T, Naito M, et al. (2006). "No association of an SDHC gene polymorphism with gastric cancer.". Asian Pac. J. Cancer Prev. 7 (4): 525–8. PMID 17250422. 
  • Cascán A, Pita G, Burnichon N, et al. (2009). "Genetics of pheochromocytoma and paraganglioma in Spanish patients.". J. Clin. Endocrinol. Metab. 94 (5): 1701–5. doi:10.1210/jc.2008-2756. PMID 19258401. 
  • Boedeker CC, Neumann HP, Maier W, et al. (2007). "Malignant head and neck paragangliomas in SDHB mutation carriers.". Otolaryngol Head Neck Surg 137 (1): 126–9. doi:10.1016/j.otohns.2007.01.015. PMID 17599579. 
  • Gill AJ, Benn DE, Chou A, et al. (2010). "Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes.". Hum. Pathol. 41 (6): 805–14. doi:10.1016/j.humpath.2009.12.005. PMID 20236688. 
  • Ricketts C, Woodward ER, Killick P, et al. (2008). "Germline SDHB mutations and familial renal cell carcinoma.". J. Natl. Cancer Inst. 100 (17): 1260–2. doi:10.1093/jnci/djn254. PMID 18728283. 
  • McWhinney SR, Pasini B, Stratakis CA, (2007). "Familial gastrointestinal stromal tumors and germ-line mutations.". N. Engl. J. Med. 357 (10): 1054–6. doi:10.1056/NEJMc071191. PMID 17804857. 
  • Eng C, Kiuru M, Fernandez MJ, Aaltonen LA (2003). "A role for mitochondrial enzymes in inherited neoplasia and beyond.". Nat. Rev. Cancer 3 (3): 193–202. doi:10.1038/nrc1013. PMID 12612654. 
  • Hermsen MA, Sevilla MA, Llorente JL, et al. (2010). "Relevance of germline mutation screening in both familial and sporadic head and neck paraganglioma for early diagnosis and clinical management.". Cell. Oncol. 32 (4): 275–83. doi:10.3233/CLO-2009-0498. PMID 20208144. 
  • Brií¨re JJ, Favier J, El Ghouzzi V, et al. (2005). "Succinate dehydrogenase deficiency in human.". Cell. Mol. Life Sci. 62 (19-20): 2317–24. doi:10.1007/s00018-005-5237-6. PMID 16143825. 
  • Mannelli M, Castellano M, Schiavi F, et al. (2009). "Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.". J. Clin. Endocrinol. Metab. 94 (5): 1541–7. doi:10.1210/jc.2008-2419. PMID 19223516. 
  • Richalet JP, Gimenez-Roqueplo AP, Peyrard S, et al. (2009). "A role for succinate dehydrogenase genes in low chemoresponsiveness to hypoxia?". Clin. Auton. Res. 19 (6): 335–42. doi:10.1007/s10286-009-0028-z. PMID 19768395. 
  • Pigny P, Cardot-Bauters C, Do Cao C, et al. (2009). "Should genetic testing be performed in each patient with sporadic pheochromocytoma at presentation?". Eur. J. Endocrinol. 160 (2): 227–31. doi:10.1530/EJE-08-0574. PMID 19029228. 
  • Korpershoek E, Van Nederveen FH, Dannenberg H, et al. (2006). "Genetic analyses of apparently sporadic pheochromocytomas: the Rotterdam experience.". Ann. N. Y. Acad. Sci. 1073: 138–48. doi:10.1196/annals.1353.014. PMID 17102080. 
  • Wang L, McDonnell SK, Hebbring SJ, et al. (2008). "Polymorphisms in mitochondrial genes and prostate cancer risk.". Cancer Epidemiol. Biomarkers Prev. 17 (12): 3558–66. doi:10.1158/1055-9965.EPI-08-0434. PMC 2750891. PMID 19064571. 

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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.

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.

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


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR005631

This entry represents a group of uncharacterised small proteins found in both eukaryotes and prokaryotes, including NMA1147 from Neisseria meningitidis [PUBMED:15103637] and YgfY from Escherichia coli [PUBMED:15593094]. YgfY may be involved in transcriptional regulation. The structure of these proteins consists of a complex bundle of five alpha-helices, which is composed of an up-down 3-helix bundle plus an orthogonal 2-helix bundle.

Domain organisation

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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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, 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
(149)
Full
(1961)
Representative proteomes NCBI
(1180)
Meta
(1046)
RP15
(158)
RP35
(312)
RP55
(458)
RP75
(589)
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Format an alignment

  Seed
(149)
Full
(1961)
Representative proteomes NCBI
(1180)
Meta
(1046)
RP15
(158)
RP35
(312)
RP55
(458)
RP75
(589)
Alignment:
Format:
Order:
Sequence:
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  Seed
(149)
Full
(1961)
Representative proteomes NCBI
(1180)
Meta
(1046)
RP15
(158)
RP35
(312)
RP55
(458)
RP75
(589)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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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.

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Curation and family details

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Curation View help on the curation process

Seed source: COG2938
Previous IDs: DUF339; TPR_div1;
Type: Domain
Author: Bateman A, Yeats C, McNeil M, Eberhardt R
Number in seed: 149
Number in full: 1961
Average length of the domain: 73.20 aa
Average identity of full alignment: 35 %
Average coverage of the sequence by the domain: 68.49 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.9 20.9
Trusted cut-off 22.3 21.7
Noise cut-off 20.7 19.3
Model length: 74
Family (HMM) version: 11
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Species distribution

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Interactions

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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 6 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 seqence.

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