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SDHAF2
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<h2 id="structure">Structure</h2> <p><i>SDHAF2</i> is located on the <a href="/facts/Locus_(genetics)/JcIT8wLm">q arm</a> of <a href="/facts/Chromosome_11/cB1PGjm5">chromosome 11</a> in position 12.2 and spans 16,642 base pairs.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> The <i>SDHAF2</i> gene produces a 6.7 kDa protein composed of 65 amino acids.<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a><a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> This highly conserved protein is a cofactor of <a href="/facts/Flavin_adenine_dinucleotide/uzADx3ES">flavin adenine dinucleotide</a> (FAD).<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> The structure represents a five-helix bundle with a region of well-defined conserved surface residues. This conserved region includes a negatively charged periphery and a positively charged surface, and a patch that is <a href="/facts/Hydrophobic/Ifya0CXQ">hydrophobic</a>. The region is located in <a href="/facts/Alpha_helix/7CESPIYJ">α-helices</a> I, II, and the connecting band.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> </p> <h2 id="function">Function</h2> <p>The <i>SDHAF2</i> gene encodes a mitochondrial <a href="/facts/Protein/Jxmagu3E">protein</a> associated with the <a href="/facts/Succinate_dehydrogenase/AswKYLm3">succinate dehydrogenase (SDH) complex (mitochondrial complex II)</a> in the <a href="/facts/Mitochondrial_respiratory_chain/QjcIkgeR">mitochondrial respiratory chain</a>, which plays essential roles in both the electron transport chain and the <a href="/facts/Krebs_Cycle/EGJL9NXP">Krebs (tricarboxylic acid) cycle</a>. SDHAF2 is integral in the proper function of the SDH complex, mainly in SDH-dependent respiration, and interacts with the catalytic subunit of the complex. SDHAF2 participates in the flavination of <a href="/facts/SDHA/EJrHpfsS">SDH1</a> (SDHA), another subunit of the SDH complex. It does so by incorporating the <a href="/facts/Flavin_adenine_dinucleotide/uzADx3ES">flavin adenine dinucleotide</a> (FAD) cofactor into <a href="/facts/SDHA/EJrHpfsS">SDHA</a>. Such flavination is required for a fully functional SDH complex. Knockdown of SDHAF2 leads to the loss-of-function of the SDH complex, a decrease in the enzyme complex stability, and a substantial reduction in all subunits. SDHAF2 was also found to function as a <a href="/facts/Tumor_suppressor/Awte4S51">tumor suppressor</a>.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a><a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a><a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> </p> <h2 id="clinical-significance">Clinical significance</h2> <p><i>SDHAF2</i> is a <a href="/facts/Tumor_suppressor_gene/Awte4S51">tumor suppressor gene</a>. Constitutional <a href="/facts/Mutation/Ee4NnWbY">mutations</a> in this gene cause <a href="/facts/Hereditary/t0aMmRWx">hereditary</a> <a href="/facts/Paraganglioma/QMCKIKPW">paraganglioma</a>, a neuroendocrine tumor formerly known to be linked to SDH subunit mutations. <a href="/facts/Paraganglioma/QMCKIKPW">paraganglioma</a> is a neural crest tumor usually derived from the <a href="/facts/Chemoreceptor/KC6IDxzf">chemoreceptor</a> tissue of a <a href="/facts/Paraganglion/AF9Y9xUA">paraganglion</a>, and may develop at various body sites, including the head, neck, <a href="/facts/Thorax/lwtzfc8K">thorax</a> and <a href="/facts/Abdomen/HcTzDFL0">abdomen</a>. Most commonly, they are located in the head and neck region, specifically at the <a href="/facts/Carotid_bifurcation/lndR9CgD">carotid bifurcation</a>, the <a href="/facts/Jugular_foramen/a4MDcPyQ">jugular foramen</a>, the <a href="/facts/Vagus_nerve/cKQR0rLm">vagus nerve</a>, and in the <a href="/facts/Middle_ear/H2A50utA">middle ear</a>.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> Phenotypes include excessive <a href="/facts/Catecholamine/hHFrCMgM">catecholamine</a> induced <a href="/facts/Hypertension/wlAvBfcf">hypertension</a>, dysfunction of major blood vessels and <a href="/facts/Cranial_nerve/8zAVI3Ua">cranial nerves</a>, significant <a href="/facts/Morbidity/55eeQlGL">morbidity</a>, <a href="/facts/Sweating/c5zARtaT">sweating</a>, and <a href="/facts/Palpitations/2wACMY49">palpitations</a>. In cases of extra-adrenal localization, the tumor may turn <a href="/facts/Metastatic/4dadbm6z">metastatic</a> and aggressive. Loss of <a href="/facts/Succinate_dehydrogenase/AswKYLm3">SDH complex</a> function has been known to be responsible for <a href="/facts/Paraganglioma/QMCKIKPW">paraganglioma</a>.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a> Mutations in this gene are found in the <a href="/facts/DNA/nB89Iauz">DNA</a> of only a small fraction of patients with the disease.<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a> </p> <h2 id="interactions">Interactions</h2> <p>SDHAF2 interacts with <a href="/facts/SDHA/EJrHpfsS">SDHA</a> within the SDH catalytic dimer. In addition to <a href="/facts/SDHA/EJrHpfsS">SDHA</a>, SDHAF2 has 17 <a href="/facts/Protein%E2%80%93protein_interaction/etvm9Wmg">protein–protein interactions</a>, including interactions with proteins such as <a href="/facts/IMMT/qgxrfkH0">IMMT</a>, <a href="/facts/SUCLG2/sua4SB41">SUCLG2</a>, UBINEDDSUMO1, <a href="/facts/SSX2IP/S5f0EXCf">SSX2IP</a>, and others.<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a> </p> <h2 id="further-reading">Further reading</h2> <ul><li>Baysal BE, Farr JE, Rubinstein WS, Galus RA, Johnson KA, Aston CE, Myers EN, Johnson JT, Carrau R, Kirkpatrick SJ, Myssiorek D, Singh D, Saha S, Gollin SM, Evans GA, James MR, Richard CW (January 1997). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1712548">"Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23"</a>. <i>American Journal of Human Genetics</i>. 60 (1): 121–32. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1712548">1712548</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8981955">8981955</a>.</li> <li>Gaal J, Burnichon N, Korpershoek E, Roncelin I, Bertherat J, Plouin PF, de Krijger RR, Gimenez-Roqueplo AP, Dinjens WN (March 2010). <a href="https://doi.org/10.1210%2Fjc.2009-2170">"Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas"</a>. <i>The Journal of Clinical Endocrinology and Metabolism</i>. 95 (3): 1274–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fjc.2009-2170">10.1210/jc.2009-2170</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/19915015">19915015</a>.</li> <li>Mariman EC, van Beersum SE, Cremers CW, Struycken PM, Ropers HH (January 1995). "Fine mapping of a putatively imprinted gene for familial non-chromaffin paragangliomas to chromosome 11q13.1: evidence for genetic heterogeneity". <i>Human Genetics</i>. 95 (1): 56–62. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1007%2Fbf00225075">10.1007/bf00225075</a>. <a href="/facts/Hdl_(identifier)/rdebSxmC">hdl</a>:<a href="https://hdl.handle.net/2066%2F22047">2066/22047</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/7814027">7814027</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:2324475">2324475</a>.</li> <li>Kunst HP, Rutten MH, de Mönnink JP, Hoefsloot LH, Timmers HJ, Marres HA, Jansen JC, Kremer H, Bayley JP, Cremers CW (January 2011). <a href="https://doi.org/10.1158%2F1078-0432.CCR-10-0420">"SDHAF2 (PGL2-SDH5) and hereditary head and neck paraganglioma"</a>. <i>Clinical Cancer Research</i>. 17 (2): 247–54. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1158%2F1078-0432.CCR-10-0420">10.1158/1078-0432.CCR-10-0420</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/21224366">21224366</a>.</li></ul> <p><i>This article incorporates text from the <a href="/facts/United_States_National_Library_of_Medicine/Hzty0MCX">United States National Library of Medicine</a>, which is in the <a href="/facts/Public_domain/YWKMDKw4">public domain</a>.</i> </p> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"Entrez Gene: Succinate dehydrogenase complex assembly factor 2". <a href="https://www.ncbi.nlm.nih.gov/gene/54949" target="_blank">https://www.ncbi.nlm.nih.gov/gene/54949</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>"Entrez Gene: Succinate dehydrogenase complex assembly factor 2". <a href="https://www.ncbi.nlm.nih.gov/gene/54949" target="_blank">https://www.ncbi.nlm.nih.gov/gene/54949</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076475" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076475</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-07-23. <a href="https://amino.heartproteome.org/web/protein/F5H4T4" target="_blank">https://amino.heartproteome.org/web/protein/F5H4T4</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Starker LF, Delgado-Verdugo A, Udelsman R, Björklund P, Carling T (December 2010). "Expression and somatic mutations of SDHAF2 (SDH5), a novel endocrine tumor suppressor gene in parathyroid tumors of primary hyperparathyroidism". Endocrine. 38 (3): 397–401. doi:10.1007/s12020-010-9399-0. PMID 20972721. S2CID 25914943. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Eletsky A, Jeong MY, Kim H, Lee HW, Xiao R, Pagliarini DJ, Prestegard JH, Winge DR, Montelione GT, Szyperski T (October 2012). "Solution NMR structure of yeast succinate dehydrogenase flavinylation factor Sdh5 reveals a putative Sdh1 binding site". Biochemistry. 51 (43): 8475–7. doi:10.1021/bi301171u. PMC 3667956. PMID 23062074. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667956" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667956</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>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 (August 2009). "SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma". Science. 325 (5944): 1139–42. Bibcode:2009Sci...325.1139H. doi:10.1126/science.1175689. PMC 3881419. PMID 19628817. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881419" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881419</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Bayley JP, Kunst HP, Cascon A, Sampietro ML, Gaal J, Korpershoek E, Hinojar-Gutierrez A, Timmers HJ, Hoefsloot LH, Hermsen MA, Suárez C, Hussain AK, Vriends AH, Hes FJ, Jansen JC, Tops CM, Corssmit EP, de Knijff P, Lenders JW, Cremers CW, Devilee P, Dinjens WN, de Krijger RR, Robledo M (April 2010). "SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma". The Lancet. Oncology. 11 (4): 366–72. doi:10.1016/S1470-2045(10)70007-3. PMID 20071235. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Kugelberg J, Welander J, Schiavi F, Fassina A, Bäckdahl M, Larsson C, Opocher G, Söderkvist P, Dahia PL, Neumann HP, Gimm O (March 2014). "Role of SDHAF2 and SDHD in von Hippel-Lindau associated pheochromocytomas". World Journal of Surgery. 38 (3): 724–32. doi:10.1007/s00268-013-2373-2. PMID 24322175. S2CID 11895429. <a href="http://liu.diva-portal.org/smash/get/diva2:714189/FULLTEXT01" target="_blank">http://liu.diva-portal.org/smash/get/diva2:714189/FULLTEXT01</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Pagon RA, Adam MP, Ardinger HH, et al. (1993). "Hereditary Paraganglioma-Pheochromocytoma Syndromes". PMID 20301715. {{cite journal}}: Cite journal requires |journal= (help) <a href="/wiki/PMID_(identifier)" target="_blank">/wiki/PMID_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>"SDHAF2 - Succinate dehydrogenase assembly factor 2, mitochondrial". www.uniprot.org. Retrieved 2018-07-18. <a href="https://www.uniprot.org/uniprot/Q5TEU4" target="_blank">https://www.uniprot.org/uniprot/Q5TEU4</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Kugelberg J, Welander J, Schiavi F, Fassina A, Bäckdahl M, Larsson C, Opocher G, Söderkvist P, Dahia PL, Neumann HP, Gimm O (March 2014). "Role of SDHAF2 and SDHD in von Hippel-Lindau associated pheochromocytomas". World Journal of Surgery. 38 (3): 724–32. doi:10.1007/s00268-013-2373-2. PMID 24322175. S2CID 11895429. <a href="http://liu.diva-portal.org/smash/get/diva2:714189/FULLTEXT01" target="_blank">http://liu.diva-portal.org/smash/get/diva2:714189/FULLTEXT01</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Bayley JP, Kunst HP, Cascon A, Sampietro ML, Gaal J, Korpershoek E, Hinojar-Gutierrez A, Timmers HJ, Hoefsloot LH, Hermsen MA, Suárez C, Hussain AK, Vriends AH, Hes FJ, Jansen JC, Tops CM, Corssmit EP, de Knijff P, Lenders JW, Cremers CW, Devilee P, Dinjens WN, de Krijger RR, Robledo M (April 2010). "SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma". The Lancet. Oncology. 11 (4): 366–72. doi:10.1016/S1470-2045(10)70007-3. PMID 20071235. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>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 (August 2009). "SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma". Science. 325 (5944): 1139–42. Bibcode:2009Sci...325.1139H. doi:10.1126/science.1175689. PMC 3881419. PMID 19628817. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881419" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881419</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Bayley JP, Kunst HP, Cascon A, Sampietro ML, Gaal J, Korpershoek E, Hinojar-Gutierrez A, Timmers HJ, Hoefsloot LH, Hermsen MA, Suárez C, Hussain AK, Vriends AH, Hes FJ, Jansen JC, Tops CM, Corssmit EP, de Knijff P, Lenders JW, Cremers CW, Devilee P, Dinjens WN, de Krijger RR, Robledo M (April 2010). "SDHAF2 mutations in familial and sporadic paraganglioma and phaeochromocytoma". The Lancet. Oncology. 11 (4): 366–72. doi:10.1016/S1470-2045(10)70007-3. PMID 20071235. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Kerrien S, Alam-Faruque Y, Aranda B, Bancarz I, Bridge A, Derow C, Dimmer E, Feuermann M, Friedrichsen A, Huntley R, Kohler C, Khadake J, Leroy C, Liban A, Lieftink C, Montecchi-Palazzi L, Orchard S, Risse J, Robbe K, Roechert B, Thorneycroft D, Zhang Y, Apweiler R, Hermjakob H (January 2007). "IntAct--open source resource for molecular interaction data". Nucleic Acids Research. 35 (Database issue): D561-5. CiteSeerX 10.1.1.279.8196. doi:10.1093/nar/gkl958. PMC 1751531. PMID 17145710. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751531" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751531</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> </ol>