SDHAF2

SDHAF2
Identifiers
Aliases	SDHAF2, C11orf79, PGL2, SDH5, succinate dehydrogenase complex assembly factor 2
External IDs	OMIM: 613019 MGI: 1913322 HomoloGene: 32370 GeneCards: SDHAF2
Gene location (Human)
Chr.	Chromosome 11 (human)[1]
End	61,447,529 bp[1]
Gene location (Mouse)
Chr.	Chromosome 19 (mouse)[2]
End	10,526,142 bp[2]
Gene ontology
Molecular function	• GO:0001948 protein binding;
Cellular component	• mitochondrial matrix; • mitochondrion; • nucleolus; • cytosol;
Biological process	• mitochondrial 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 pathway;
	Sources:Amigo / QuickGO
Orthologs
	54949
	66072
	ENSG00000167985
	ENSMUSG00000024668
	Q9NX18
	Q8C6I2
	NM_017841
	NM_025333
	NP_060311
	NP_079609
	Wikidata
View/Edit Human	View/Edit Mouse

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 paraganglioma.[5]

Structure

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]

Function

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]

Clinical significance

SDHAF2 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

SDHAF2 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]

gollark: The only indexing operation rust strings support is pulling UTF-8 bytes out of them.

gollark: What?

gollark: Swift?

gollark: I'll add it to your psychological profile.

gollark: I see.

References

GRCh38: Ensembl release 89: ENSG00000167985 - Ensembl, May 2017
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.
"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, 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.
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.
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.
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.
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.
Pagon RA, Adam MP, Ardinger HH, et al. (1993). "Hereditary Paraganglioma-Pheochromocytoma Syndromes". PMID 20301715. 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.