Succinate dehydrogenase complex assembly factor 2, formerly known as SDH5 and also known as SDH assembly factor 2 or SDHAF2 is a protein that in humans is encoded by the SDHAF2 gene. This gene encodes a mitochondrial protein needed for the flavination of a succinate dehydrogenase complex subunit required for activity of the complex. Mutations in this gene are associated with pheochromocytoma and paraganglioma.[5]
SDHAF2 is located on the q arm of chromosome 11 in position 12.2 and spans 16,642 base pairs.[5] The SDHAF2 gene produces a 6.7 kDa protein composed of 65 amino acids.[6][7] This highly conserved protein is a cofactor of flavin adenine dinucleotide (FAD).[8] 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 hydrophobic. The region is located in α-helices I, II, and the connecting band.[9]
Functionedit
The SDHAF2 gene encodes a mitochondrial protein associated with the succinate dehydrogenase (SDH) complex (mitochondrial complex II) in the mitochondrial respiratory chain, which plays essential roles in both the electron transport chain and the Krebs (tricarboxylic acid) cycle. 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 SDH1 (SDHA), another subunit of the SDH complex. It does so by incorporating the flavin adenine dinucleotide (FAD) cofactor into SDHA. 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 tumor suppressor.[10][11][12][13]
^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. PMC4076475. PMID 23965338.
^Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". amino.heartproteome.org. Retrieved 2018-07-23.
^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.
^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. PMC3667956. PMID 23062074.
^ ab 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. PMC3881419. PMID 19628817.
^ abcBayley 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.
^ abKugelberg 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.
^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. CiteSeerX10.1.1.279.8196. doi:10.1093/nar/gkl958. PMC1751531. PMID 17145710.
Further readingedit
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). "Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23". American Journal of Human Genetics. 60 (1): 121–32. PMC1712548. PMID 8981955.
Gaal J, Burnichon N, Korpershoek E, Roncelin I, Bertherat J, Plouin PF, de Krijger RR, Gimenez-Roqueplo AP, Dinjens WN (March 2010). "Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas". The Journal of Clinical Endocrinology and Metabolism. 95 (3): 1274–8. doi:10.1210/jc.2009-2170. PMID 19915015.
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". Human Genetics. 95 (1): 56–62. doi:10.1007/bf00225075. hdl:2066/22047. PMID 7814027. S2CID 2324475.
Kunst HP, Rutten MH, de Mönnink JP, Hoefsloot LH, Timmers HJ, Marres HA, Jansen JC, Kremer H, Bayley JP, Cremers CW (January 2011). "SDHAF2 (PGL2-SDH5) and hereditary head and neck paraganglioma". Clinical Cancer Research. 17 (2): 247–54. doi:10.1158/1078-0432.CCR-10-0420. PMID 21224366.
sdhaf2, succinate, dehydrogenase, complex, assembly, factor, formerly, known, sdh5, also, known, assembly, factor, protein, that, humans, encoded, gene, this, gene, encodes, mitochondrial, protein, needed, flavination, succinate, dehydrogenase, complex, subuni. Succinate dehydrogenase complex assembly factor 2 formerly known as SDH5 and also known as SDH assembly factor 2 or SDHAF2 is a protein that in humans is encoded by the SDHAF2 gene This gene encodes a mitochondrial protein needed for the flavination of a succinate dehydrogenase complex subunit required for activity of the complex Mutations in this gene are associated with pheochromocytoma and paraganglioma 5 SDHAF2IdentifiersAliasesSDHAF2 C11orf79 PGL2 SDH5 succinate dehydrogenase complex assembly factor 2External IDsOMIM 613019 MGI 1913322 HomoloGene 32370 GeneCards SDHAF2Gene location Human Chr Chromosome 11 human 1 Band11q12 2Start61 430 042 bp 1 End61 446 733 bp 1 Gene location Mouse Chr Chromosome 19 mouse 2 Band19 19 AStart10 477 898 bp 2 End10 503 506 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inislet of Langerhansanterior pituitarymonocyteright adrenal glandleft adrenal glandgastrocnemius muscleright lobe of liverrectumsmooth muscle tissueright lobe of thyroid glandTop expressed inotic placodesacculeinterventricular septumsternocleidomastoid musclemyocardium of ventriclecardiac musclestemporal muscledigastric musclequadriceps femoris musclesoleus muscleMore reference expression dataBioGPSn aGene ontologyMolecular functionprotein bindingCellular componentmitochondrial matrix mitochondrion nucleolus cytosolBiological processmitochondrial electron transport succinate to ubiquinone protein FAD linkage tricarboxylic acid cycle mitochondrial respiratory chain complex II assembly protein dephosphorylation negative regulation of epithelial to mesenchymal transition negative regulation of canonical Wnt signaling pathwaySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez5494966072EnsemblENSG00000167985ENSMUSG00000024668UniProtQ9NX18Q8C6I2RefSeq mRNA NM 017841NM 025333RefSeq protein NP 060311NP 079609Location UCSC Chr 11 61 43 61 45 MbChr 19 10 48 10 5 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Structure 2 Function 3 Clinical significance 4 Interactions 5 References 6 Further readingStructure editSDHAF2 is located on the q arm of chromosome 11 in position 12 2 and spans 16 642 base pairs 5 The SDHAF2 gene produces a 6 7 kDa protein composed of 65 amino acids 6 7 This highly conserved protein is a cofactor of flavin adenine dinucleotide FAD 8 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 hydrophobic The region is located in a helices I II and the connecting band 9 Function editThe SDHAF2 gene encodes a mitochondrial protein associated with the succinate dehydrogenase SDH complex mitochondrial complex II in the mitochondrial respiratory chain which plays essential roles in both the electron transport chain and the Krebs tricarboxylic acid cycle 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 SDH1 SDHA another subunit of the SDH complex It does so by incorporating the flavin adenine dinucleotide FAD cofactor into SDHA 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 tumor suppressor 10 11 12 13 Clinical significance editSDHAF2 is a tumor suppressor gene Constitutional mutations in this gene cause hereditary paraganglioma a neuroendocrine tumor formerly known to be linked to SDH subunit mutations paraganglioma is a neural crest tumor usually derived from the chemoreceptor tissue of a paraganglion and may develop at various body sites including the head neck thorax and abdomen Most commonly they are located in the head and neck region specifically at the carotid bifurcation the jugular foramen the vagus nerve and in the middle ear 14 Phenotypes include excessive catecholamine induced hypertension dysfunction of major blood vessels and cranial nerves significant morbidity sweating and palpitations In cases of extra adrenal localization the tumor may turn metastatic and aggressive Loss of SDH complex function has been known to be responsible for paraganglioma 12 11 10 Mutations in this gene are found in the DNA of only a small fraction of patients with the disease 11 Interactions editSDHAF2 interacts with SDHA within the SDH catalytic dimer In addition to SDHA SDHAF2 has 17 protein protein interactions including interactions with proteins such as IMMT SUCLG2 UBINEDDSUMO1 SSX2IP and others 15 References edit a b c GRCh38 Ensembl release 89 ENSG00000167985 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000024668 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Entrez Gene Succinate dehydrogenase complex assembly factor 2 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 Yao Daniel Cardiac Organellar Protein Atlas Knowledgebase COPaKB Protein Information amino heartproteome org Retrieved 2018 07 23 Starker LF Delgado Verdugo A Udelsman R Bjorklund 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 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 b 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 b c Bayley JP Kunst HP Cascon A Sampietro ML Gaal J Korpershoek E Hinojar Gutierrez A Timmers HJ Hoefsloot LH Hermsen MA Suarez 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 b Kugelberg J Welander J Schiavi F Fassina A Backdahl M Larsson C Opocher G Soderkvist 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 Pagon RA Adam MP Ardinger HH et al 1993 Hereditary Paraganglioma Pheochromocytoma Syndromes PMID 20301715 a href Template Cite journal html title Template Cite journal cite journal a Cite journal requires journal help SDHAF2 Succinate dehydrogenase assembly factor 2 mitochondrial www uniprot org Retrieved 2018 07 18 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 Further reading editBaysal 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 Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas on chromosome 11q23 American Journal of Human Genetics 60 1 121 32 PMC 1712548 PMID 8981955 Gaal J Burnichon N Korpershoek E Roncelin I Bertherat J Plouin PF de Krijger RR Gimenez Roqueplo AP Dinjens WN March 2010 Isocitrate dehydrogenase mutations are rare in pheochromocytomas and paragangliomas The Journal of Clinical Endocrinology and Metabolism 95 3 1274 8 doi 10 1210 jc 2009 2170 PMID 19915015 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 Human Genetics 95 1 56 62 doi 10 1007 bf00225075 hdl 2066 22047 PMID 7814027 S2CID 2324475 Kunst HP Rutten MH de Monnink JP Hoefsloot LH Timmers HJ Marres HA Jansen JC Kremer H Bayley JP Cremers CW January 2011 SDHAF2 PGL2 SDH5 and hereditary head and neck paraganglioma Clinical Cancer Research 17 2 247 54 doi 10 1158 1078 0432 CCR 10 0420 PMID 21224366 This article incorporates text from the United States National Library of Medicine which is in the public domain Retrieved from https en wikipedia org w index php title SDHAF2 amp oldid 1213633954, wikipedia, wiki, book, books, library,
