Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial

Details

Name
Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
Synonyms
  • 1.3.5.1
  • Flavoprotein subunit of complex II
  • Fp
  • Malate dehydrogenase [quinone] flavoprotein subunit
  • SDH2
  • SDHF
Gene Name
SDHA
UniProtKB Entry
P31040Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0000351|Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
MSGVRGLSRLLSARRLALAKAWPTVLQTGTRGFHFTVDGNKRASAKVSDSISAQYPVVDH
EFDAVVVGAGGAGLRAAFGLSEAGFNTACVTKLFPTRSHTVAAQGGINAALGNMEEDNWR
WHFYDTVKGSDWLGDQDAIHYMTEQAPAAVVELENYGMPFSRTEDGKIYQRAFGGQSLKF
GKGGQAHRCCCVADRTGHSLLHTLYGRSLRYDTSYFVEYFALDLLMENGECRGVIALCIE
DGSIHRIRAKNTVVATGGYGRTYFSCTSAHTSTGDGTAMITRAGLPCQDLEFVQFHPTGI
YGAGCLITEGCRGEGGILINSQGERFMERYAPVAKDLASRDVVSRSMTLEIREGRGCGPE
KDHVYLQLHHLPPEQLATRLPGISETAMIFAGVDVTKEPIPVLPTVHYNMGGIPTNYKGQ
VLRHVNGQDQIVPGLYACGEAACASVHGANRLGANSLLDLVVFGRACALSIEESCRPGDK
VPPIKPNAGEESVMNLDKLRFADGSIRTSELRLSMQKSMQNHAAVFRVGSVLQEGCGKIS
KLYGDLKHLKTFDRGMVWNTDLVETLELQNLMLCALQTIYGAEARKESRGAHAREDYKVR
IDEYDYSKPIQGQQKKPFEEHWRKHTLSYVDVGTGKVTLEYRPVIDKTLNEADCATVPPA
IRSY
Number of residues
664
Molecular Weight
72690.975
Theoretical pI
7.41
GO Classification
Functions
electron transfer activity / succinate dehydrogenase (quinone) activity
Processes
mitochondrial electron transport, succinate to ubiquinone / proton motive force-driven mitochondrial ATP synthesis
Components
nucleolus
General Function
Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) (Probable) (PubMed:24781757). SDH also oxidizes malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate (By similarity). Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerized into keto-oxaloacetate (By similarity). Can act as a tumor suppressor (PubMed:20484225)
Specific Function
Electron transfer activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion inner membrane
Gene sequence
>lcl|BSEQ0016026|Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial (SDHA)
ATGTCGGGGGTCCGGGGCCTGTCGCGGCTGCTGAGCGCTCGGCGCCTGGCGCTGGCCAAG
GCGTGGCCAACAGTGTTGCAAACAGGAACCCGAGGTTTTCACTTCACTGTTGATGGGAAC
AAGAGGGCATCTGCTAAAGTTTCAGATTCCATTTCTGCTCAGTATCCAGTAGTGGATCAT
GAATTTGATGCAGTGGTGGTAGGCGCTGGAGGGGCAGGCTTGCGAGCTGCATTTGGCCTT
TCTGAGGCAGGGTTTAATACAGCATGTGTTACCAAGCTGTTTCCTACCAGGTCACACACT
GTTGCAGCACAGCTAGAAAATTATGGCATGCCGTTTAGCAGAACTGAAGATGGGAAGATT
TATCAGCGTGCATTTGGTGGACAGAGCCTCAAGTTTGGAAAGGGCGGGCAGGCCCATCGG
TGCTGCTGTGTGGCTGATCGGACTGGCCACTCGCTATTGCACACCTTATATGGAAGGTCT
CTGCGATATGATACCAGCTATTTTGTGGAGTATTTTGCCTTGGATCTCCTGATGGAGAAT
GGGGAGTGCCGTGGTGTCATCGCACTGTGCATAGAGGACGGGTCCATCCATCGCATAAGA
GCAAAGAACACTGTTGTTGCCACAGGAGGCTACGGGCGCACCTACTTCAGCTGCACGTCT
GCCCACACCAGCACTGGCGACGGCACGGCCATGATCACCAGGGCAGGCCTTCCTTGCCAG
GACCTAGAGTTTGTTCAGTTCCACCCTACAGGCATATATGGTGCTGGTTGTCTCATTACG
GAAGGATGTCGTGGAGAGGGAGGCATTCTCATTAACAGTCAAGGCGAAAGGTTTATGGAG
CGATACGCCCCTGTCGCGAAGGACCTGGCGTCTAGAGATGTGGTGTCTCGGTCCATGACT
CTGGAGATCCGAGAAGGAAGAGGCTGTGGCCCTGAGAAAGATCACGTCTACCTGCAGCTG
CACCACCTACCTCCAGAGCAGCTGGCCACGCGCCTGCCTGGCATTTCAGAGACAGCCATG
ATCTTCGCTGGCGTGGACGTCACGAAGGAGCCGATCCCTGTCCTCCCCACCGTGCATTAT
AACATGGGCGGCATTCCCACCAACTACAAGGGGCAGGTCCTGAGGCACGTGAATGGCCAG
GATCAGATTGTGCCCGGCCTGTACGCCTGTGGGGAGGCCGCCTGTGCCTCGGTACATGGT
GCCAACCGCCTCGGGGCAAACTCGCTCTTGGACCTGGTTGTCTTTGGTCGGGCATGTGCC
CTGAGCATCGAAGAGTCATGCAGGCCTGGAGATAAAGTCCCTCCAATTAAACCAAACGCT
GGGGAAGAATCTGTCATGAATCTTGACAAATTGAGATTTGCTGATGGAAGCATAAGAACA
TCGGAACTGCGACTCAGCATGCAGAAGTCAATGCAAAATCATGCTGCCGTGTTCCGTGTG
GGAAGCGTGTTGCAAGAAGGTTGTGGGAAAATCAGCAAGCTCTATGGAGACCTAAAGCAC
CTGAAGACGTTCGACCGGGGAATGGTCTGGAACACGGACCTGGTGGAGACCCTGGAGCTG
CAGAACCTGATGCTGTGTGCGCTGCAGACCATCTACGGAGCAGAGGCACGGAAGGAGTCA
CGGGGCGCGCATGCCAGGGAAGACTACAAGGTGCGGATTGATGAGTACGATTACTCCAAG
CCCATCCAGGGGCAACAGAAGAAGCCCTTTGAGGAGCACTGGAGGAAGCACACCCTGTCC
TATGTGGACGTTGGCACTGGGAAGGTCACTCTGGAATATAGACCCGTGATCGACAAAACT
TTGAACGAGGCTGACTGTGCCACCGTCCCGCCAGCCATTCGCTCCTACTGA
Chromosome Location
5
Locus
5p15.33
External Identifiers
ResourceLink
UniProtKB IDP31040
UniProtKB Entry NameSDHA_HUMAN
GenBank Protein ID506338
GenBank Gene IDD30648
GeneCard IDSDHA
GenAtlas IDSDHA
HGNC IDHGNC:10680
PDB ID(s)6VAX, 8DYD, 8DYE, 8GS8
KEGG IDhsa:6389
NCBI Gene ID6389
General References
  1. Hirawake H, Wang H, Kuramochi T, Kojima S, Kita K: Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the flavoprotein (Fp) subunit of liver mitochondria. J Biochem. 1994 Jul;116(1):221-7. [Article]
  2. Morris AA, Farnsworth L, Ackrell BA, Turnbull DM, Birch-Machin MA: The cDNA sequence of the flavoprotein subunit of human heart succinate dehydrogenase. Biochim Biophys Acta. 1994 Mar 29;1185(1):125-8. [Article]
  3. Parfait B, Chretien D, Rotig A, Marsac C, Munnich A, Rustin P: Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome. Hum Genet. 2000 Feb;106(2):236-43. [Article]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  5. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Bourgeron T, Rustin P, Chretien D, Birch-Machin M, Bourgeois M, Viegas-Pequignot E, Munnich A, Rotig A: Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nat Genet. 1995 Oct;11(2):144-9. [Article]
  8. Aboulaich N, Vainonen JP, Stralfors P, Vener AV: Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes. Biochem J. 2004 Oct 15;383(Pt 2):237-48. [Article]
  9. 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: SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma. Science. 2009 Aug 28;325(5944):1139-42. doi: 10.1126/science.1175689. Epub 2009 Jul 23. [Article]
  10. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  11. Burnichon N, Briere JJ, Libe R, Vescovo L, Riviere J, Tissier F, Jouanno E, Jeunemaitre X, Benit P, Tzagoloff A, Rustin P, Bertherat J, Favier J, Gimenez-Roqueplo AP: SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet. 2010 Aug 1;19(15):3011-20. doi: 10.1093/hmg/ddq206. Epub 2010 May 18. [Article]
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  13. Ogura M, Yamaki J, Homma MK, Homma Y: Mitochondrial c-Src regulates cell survival through phosphorylation of respiratory chain components. Biochem J. 2012 Oct 15;447(2):281-9. [Article]
  14. Sciacovelli M, Guzzo G, Morello V, Frezza C, Zheng L, Nannini N, Calabrese F, Laudiero G, Esposito F, Landriscina M, Defilippi P, Bernardi P, Rasola A: The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase. Cell Metab. 2013 Jun 4;17(6):988-99. doi: 10.1016/j.cmet.2013.04.019. [Article]
  15. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  16. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  17. Van Coster R, Seneca S, Smet J, Van Hecke R, Gerlo E, Devreese B, Van Beeumen J, Leroy JG, De Meirleir L, Lissens W: Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein gene causes instability of the respiratory chain complex II. Am J Med Genet A. 2003 Jul 1;120A(1):13-8. [Article]
  18. Levitas A, Muhammad E, Harel G, Saada A, Caspi VC, Manor E, Beck JC, Sheffield V, Parvari R: Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase. Eur J Hum Genet. 2010 Oct;18(10):1160-5. doi: 10.1038/ejhg.2010.83. Epub 2010 Jun 16. [Article]
  19. Renkema GH, Wortmann SB, Smeets RJ, Venselaar H, Antoine M, Visser G, Ben-Omran T, van den Heuvel LP, Timmers HJ, Smeitink JA, Rodenburg RJ: SDHA mutations causing a multisystem mitochondrial disease: novel mutations and genetic overlap with hereditary tumors. Eur J Hum Genet. 2015 Feb;23(2):202-9. doi: 10.1038/ejhg.2014.80. Epub 2014 Apr 30. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial (Humans)protein
primary
Succinate dehydrogenase (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Carboxinapproved, experimentalunknowntargetDetails
ThenoyltrifluoroacetoneexperimentalunknowntargetDetails
2-Hexyloxy-6-Hydroxymethyl-Tetrahydro-Pyran-3,4,5-TriolexperimentalunknowntargetDetails
Ubiquinone Q1experimentalunknowntargetDetails
Ubidecarenoneapproved, investigational, nutraceuticalyestargetcofactorDetails
Succinic acidapproved, nutraceuticalunknownenzymesubstrateDetails