Summary: Flavinator of succinate dehydrogenase
This is the Wikipedia entry entitled "Succinate dehydrogenase complex subunit C". More...
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Succinate dehydrogenase complex subunit C Edit Wikipedia article
|Succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa|
PDB rendering based on 1zp0.
|Symbols||; CYB560; CYBL; PGL3; QPS1; SDH3|
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.
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.
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.
SDHC acts as an intermediate in the basic SDH enzyme action:
- SDHA converts succinate to fumarate as part of the Citric Acid Cycle. This reaction also converts FAD to FADH2.
- 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
- Finally the electrons are transferred to the Ubiquinone (Q) pool via the SDHC/SDHD subunits.
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78".
- "Entrez Gene: succinate dehydrogenase complex".
- 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.
- 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.
- 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. PMC 3419008. 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.
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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 . 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 . This family was previously annotated in Pfam as being a divergent TPR repeat but structural evidence has indicated this is not true.
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
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.
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|Previous IDs:||DUF339; TPR_div1;|
|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 build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||11|
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