ID SDHA_HUMAN Reviewed; 664 AA. AC P31040; A8K5J6; B4DJ60; E9PBJ5; Q16395; Q59GW8; Q8IW48; Q9UMY5; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 2. DT 27-MAR-2024, entry version 242. DE RecName: Full=Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial; DE EC=1.3.5.1 {ECO:0000305|PubMed:24781757}; DE AltName: Full=Flavoprotein subunit of complex II; DE Short=Fp; DE Flags: Precursor; GN Name=SDHA; Synonyms=SDH2, SDHF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=7798181; DOI=10.1093/oxfordjournals.jbchem.a124497; RA Hirawake H., Wang H., Kuramochi T., Kojima S., Kita K.; RT "Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of RT the flavoprotein (Fp) subunit of liver mitochondria."; RL J. Biochem. 116:221-227(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS PHE-629 AND ILE-657. RC TISSUE=Heart; RX PubMed=8142412; DOI=10.1016/0005-2728(94)90203-8; RA Morris A.A.M., Farnsworth L., Ackrell B.A.C., Turnbull D.M., RA Birch-MacHin M.A.; RT "The cDNA sequence of the flavoprotein subunit of human heart succinate RT dehydrogenase."; RL Biochim. Biophys. Acta 1185:125-128(1994). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LS VAL-524. RX PubMed=10746566; DOI=10.1007/s004390051033; RA Parfait B., Chretien D., Roetig A., Marsac C., Munnich A., Rustin P.; RT "Compound heterozygous mutations in the flavoprotein gene of the RT respiratory chain complex II in a patient with Leigh syndrome."; RL Hum. Genet. 106:236-243(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP VAL-38. RC TISSUE=Substantia nigra, and Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PHE-629. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT RP PHE-629. RC TISSUE=Colon, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PRELIMINARY PARTIAL NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RA Malcovati M., Marchetti L., Zanelli E., Tenchini M.L.; RT "Cloning of the flavoprotein subunit of human succinate dehydrogenase."; RL (In) Curti B., Ronchi S., Zanetti G. (eds.); RL Flavins and flavoproteins 1990, pp.727-730, Walter de Gruyter, Berlin RL (1991). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 546-562, AND VARIANT LS TRP-554. RX PubMed=7550341; DOI=10.1038/ng1095-144; RA Bourgeron T., Rustin P., Chretien D., Birch-MacHin M.A., Bourgeois M., RA Viegas-Pequignot E., Munnich A., Roetig A.; RT "Mutation of a nuclear succinate dehydrogenase gene results in RT mitochondrial respiratory chain deficiency."; RL Nat. Genet. 11:144-149(1995). RN [11] RP PROTEIN SEQUENCE OF 76-92 AND 398-418. RC TISSUE=Adipocyte; RX PubMed=15242332; DOI=10.1042/bj20040647; RA Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.; RT "Vectorial proteomics reveal targeting, phosphorylation and specific RT fragmentation of polymerase I and transcript release factor (PTRF) at the RT surface of caveolae in human adipocytes."; RL Biochem. J. 383:237-248(2004). RN [12] RP INTERACTION WITH SDHAF2. RX PubMed=19628817; DOI=10.1126/science.1175689; RA Hao H.-X., Khalimonchuk O., Schraders M., Dephoure N., Bayley J.-P., RA Kunst H., Devilee P., Cremers C.W.R.J., Schiffman J.D., Bentz B.G., RA Gygi S.P., Winge D.R., Kremer H., Rutter J.; RT "SDH5, a gene required for flavination of succinate dehydrogenase, is RT mutated in paraganglioma."; RL Science 325:1139-1142(2009). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-179; LYS-335; LYS-541 AND RP LYS-608, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [14] RP FUNCTION, VARIANT PPGL5 TRP-589, AND CHARACTERIZATION OF VARIANT PPGL5 RP TRP-589. RX PubMed=20484225; DOI=10.1093/hmg/ddq206; RA Burnichon N., Briere J.J., Libe R., Vescovo L., Riviere J., Tissier F., RA Jouanno E., Jeunemaitre X., Benit P., Tzagoloff A., Rustin P., RA Bertherat J., Favier J., Gimenez-Roqueplo A.P.; RT "SDHA is a tumor suppressor gene causing paraganglioma."; RL Hum. Mol. Genet. 19:3011-3020(2010). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP PHOSPHORYLATION AT TYR-215 BY SRC. RX PubMed=22823520; DOI=10.1042/bj20120509; RA Ogura M., Yamaki J., Homma M.K., Homma Y.; RT "Mitochondrial c-Src regulates cell survival through phosphorylation of RT respiratory chain components."; RL Biochem. J. 447:281-289(2012). RN [17] RP INTERACTION WITH TRAP1. RX PubMed=23747254; DOI=10.1016/j.cmet.2013.04.019; RA Sciacovelli M., Guzzo G., Morello V., Frezza C., Zheng L., Nannini N., RA Calabrese F., Laudiero G., Esposito F., Landriscina M., Defilippi P., RA Bernardi P., Rasola A.; RT "The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting RT succinate dehydrogenase."; RL Cell Metab. 17:988-999(2013). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [20] RP INTERACTION WITH LACC1. RX PubMed=28593945; DOI=10.1038/ncomms15614; RA Lahiri A., Hedl M., Yan J., Abraham C.; RT "Human LACC1 increases innate receptor-induced responses and a LACC1 RT disease-risk variant modulates these outcomes."; RL Nat. Commun. 8:15614-15614(2017). RN [21] RP INVOLVEMENT IN NDAXOA, AND VARIANT NDAXOA CYS-451. RX PubMed=10976639; RX DOI=10.1002/1531-8249(200009)48:3<330::aid-ana7>3.3.co;2-1; RA Birch-Machin M.A., Taylor R.W., Cochran B., Ackrell B.A., Turnbull D.M.; RT "Late-onset optic atrophy, ataxia, and myopathy associated with a mutation RT of a complex II gene."; RL Ann. Neurol. 48:330-335(2000). RN [22] RP VARIANT MC2DN1 GLU-555. RX PubMed=12794685; DOI=10.1002/ajmg.a.10202; RA Van Coster R., Seneca S., Smet J., Van Hecke R., Gerlo E., Devreese B., RA Van Beeumen J., Leroy J.G., De Meirleir L., Lissens W.; RT "Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein RT gene causes instability of the respiratory chain complex II."; RL Am. J. Med. Genet. A 120:13-18(2003). RN [23] RP VARIANT CMD1GG GLU-555. RX PubMed=20551992; DOI=10.1038/ejhg.2010.83; RA Levitas A., Muhammad E., Harel G., Saada A., Caspi V.C., Manor E., RA Beck J.C., Sheffield V., Parvari R.; RT "Familial neonatal isolated cardiomyopathy caused by a mutation in the RT flavoprotein subunit of succinate dehydrogenase."; RL Eur. J. Hum. Genet. 18:1160-1165(2010). RN [24] RP VARIANT LS GLY-189, CHARACTERIZATION OF VARIANT LS GLY-189, FUNCTION, RP CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=24781757; DOI=10.1038/ejhg.2014.80; RA Renkema G.H., Wortmann S.B., Smeets R.J., Venselaar H., Antoine M., RA Visser G., Ben-Omran T., van den Heuvel L.P., Timmers H.J., Smeitink J.A., RA Rodenburg R.J.; RT "SDHA mutations causing a multisystem mitochondrial disease: novel RT mutations and genetic overlap with hereditary tumors."; RL Eur. J. Hum. Genet. 23:202-209(2015). RN [25] RP VARIANT ILE-508, AND VARIANT MC2DN1 LEU-509. RX PubMed=22972948; DOI=10.1136/jmedgenet-2012-101146; RA Alston C.L., Davison J.E., Meloni F., van der Westhuizen F.H., He L., RA Hornig-Do H.T., Peet A.C., Gissen P., Goffrini P., Ferrero I., Wassmer E., RA McFarland R., Taylor R.W.; RT "Recessive germline SDHA and SDHB mutations causing leukodystrophy and RT isolated mitochondrial complex II deficiency."; RL J. Med. Genet. 49:569-577(2012). RN [26] RP VARIANT ILE-508, AND VARIANT MC2DN1 LEU-509. RX PubMed=26642834; DOI=10.1002/ana.24572; RG SDH Study Group; RA Helman G., Caldovic L., Whitehead M.T., Simons C., Brockmann K., RA Edvardson S., Bai R., Moroni I., Taylor J.M., Van Haren K., Taft R.J., RA Vanderver A., van der Knaap M.S.; RT "Magnetic resonance imaging spectrum of succinate dehydrogenase-related RT infantile leukoencephalopathy."; RL Ann. Neurol. 79:379-386(2016). RN [27] RP VARIANT NDAXOA CYS-451. RX PubMed=27683074; DOI=10.1002/ajmg.a.37986; RA Courage C., Jackson C.B., Hahn D., Euro L., Nuoffer J.M., Gallati S., RA Schaller A.; RT "SDHA mutation with dominant transmission results in complex II deficiency RT with ocular, cardiac, and neurologic involvement."; RL Am. J. Med. Genet. A 173:225-230(2017). CC -!- FUNCTION: Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) CC that is involved in complex II of the mitochondrial electron transport CC chain and is responsible for transferring electrons from succinate to CC ubiquinone (coenzyme Q) (PubMed:24781757). Can act as a tumor CC suppressor (PubMed:20484225). {ECO:0000269|PubMed:20484225, CC ECO:0000305|PubMed:24781757}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a quinone + succinate = a quinol + fumarate; CC Xref=Rhea:RHEA:40523, ChEBI:CHEBI:24646, ChEBI:CHEBI:29806, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:132124; EC=1.3.5.1; CC Evidence={ECO:0000305|PubMed:24781757}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000250|UniProtKB:Q0QF01}; CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; fumarate CC from succinate (eukaryal route): step 1/1. CC {ECO:0000305|PubMed:24781757}. CC -!- SUBUNIT: Component of complex II composed of four subunits: the CC flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome CC b560 composed of SDHC and SDHD (By similarity). Interacts with CC SDHAF2/SDH5; interaction is required for FAD attachment CC (PubMed:19628817). Interacts with TRAP1 (PubMed:23747254). Interacts CC with LACC1 (PubMed:28593945). {ECO:0000250|UniProtKB:Q0QF01, CC ECO:0000269|PubMed:19628817, ECO:0000269|PubMed:23747254, CC ECO:0000269|PubMed:28593945}. CC -!- INTERACTION: CC P31040; P13569: CFTR; NbExp=15; IntAct=EBI-1057265, EBI-349854; CC P31040; P26045: PTPN3; NbExp=2; IntAct=EBI-1057265, EBI-1047946; CC P31040; Q9NX18: SDHAF2; NbExp=3; IntAct=EBI-1057265, EBI-713250; CC P31040; P21912: SDHB; NbExp=9; IntAct=EBI-1057265, EBI-1056481; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000250|UniProtKB:Q0QF01}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q0QF01}; Matrix side CC {ECO:0000250|UniProtKB:Q0QF01}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P31040-1; Sequence=Displayed; CC Name=2; CC IsoId=P31040-2; Sequence=VSP_055077; CC Name=3; CC IsoId=P31040-3; Sequence=VSP_055078; CC -!- PTM: Phosphorylation at Tyr-215 is important for efficient electron CC transfer in complex II and the prevention of ROS generation. CC {ECO:0000269|PubMed:22823520}. CC -!- PTM: Acetylated. Deacetylated by SIRT3. {ECO:0000250|UniProtKB:Q8K2B3}. CC -!- DISEASE: Mitochondrial complex II deficiency, nuclear type 1 (MC2DN1) CC [MIM:252011]: A disorder of the mitochondrial respiratory chain with CC heterogeneous clinical manifestations. Clinical features include CC psychomotor regression in infants, poor growth with lack of speech CC development, severe spastic quadriplegia, dystonia, progressive CC leukoencephalopathy, muscle weakness, exercise intolerance, CC cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre CC syndrome. MC2DN1 inheritance is autosomal recessive. CC {ECO:0000269|PubMed:12794685, ECO:0000269|PubMed:22972948, CC ECO:0000269|PubMed:26642834}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive CC neurodegenerative disorder characterized by the presence of focal, CC bilateral lesions in one or more areas of the central nervous system CC including the brainstem, thalamus, basal ganglia, cerebellum and spinal CC cord. Clinical features depend on which areas of the central nervous CC system are involved and include subacute onset of psychomotor CC retardation, hypotonia, ataxia, weakness, vision loss, eye movement CC abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:10746566, CC ECO:0000269|PubMed:24781757, ECO:0000269|PubMed:7550341}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Cardiomyopathy, dilated, 1GG (CMD1GG) [MIM:613642]: A disorder CC characterized by ventricular dilation and impaired systolic function, CC resulting in congestive heart failure and arrhythmia. Patients are at CC risk of premature death. {ECO:0000269|PubMed:20551992}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Pheochromocytoma/paraganglioma syndrome 5 (PPGL5) CC [MIM:614165]: A form of pheochromocytoma/paraganglioma syndrome, a CC tumor predisposition syndrome characterized by the development of CC neuroendocrine tumors, usually in adulthood. Pheochromocytomas are CC catecholamine-producing tumors that arise from chromaffin cells in the CC adrenal medulla. Paragangliomas develop from sympathetic paraganglia in CC the thorax, abdomen, and pelvis, as well as from parasympathetic CC paraganglia in the head and neck. PPGL5 inheritance is autosomal CC dominant. {ECO:0000269|PubMed:20484225}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Neurodegeneration with ataxia and late-onset optic atrophy CC (NDAXOA) [MIM:619259]: An autosomal dominant disorder characterized by CC slowly progressive cerebellar and gait ataxia, optic atrophy, and CC myopathy or myalgia. Additional features can include cardiomyopathy, CC psychiatric disturbances, and peripheral sensory impairment. Disease CC onset is usually in mid-adulthood. {ECO:0000269|PubMed:10976639, CC ECO:0000269|PubMed:27683074}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the FAD-dependent oxidoreductase 2 family. CC FRD/SDH subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD92228.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAA37886.1; Type=Miscellaneous discrepancy; Note=Differs extensively from that shown.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=TCA Cycle Gene Mutation Database; CC URL="https://databases.lovd.nl/shared/genes/SDHA"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D30648; BAA06332.1; -; mRNA. DR EMBL; L21936; AAA20683.1; -; mRNA. DR EMBL; AF171030; AAD51006.1; -; Genomic_DNA. DR EMBL; AF171017; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171018; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171019; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171020; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171021; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171022; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171023; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171024; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171025; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171026; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171027; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171028; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AF171029; AAD51006.1; JOINED; Genomic_DNA. DR EMBL; AK291311; BAF84000.1; -; mRNA. DR EMBL; AK295937; BAG58722.1; -; mRNA. DR EMBL; AB208991; BAD92228.1; ALT_INIT; mRNA. DR EMBL; AC021087; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471235; EAW50983.1; -; Genomic_DNA. DR EMBL; BC001380; AAH01380.1; -; mRNA. DR EMBL; BC041016; AAH41016.1; -; mRNA. DR EMBL; X53943; CAA37886.1; ALT_SEQ; mRNA. DR EMBL; S79641; AAB35332.1; -; Genomic_DNA. DR CCDS; CCDS3853.1; -. [P31040-1] DR CCDS; CCDS77992.1; -. [P31040-2] DR PIR; JX0336; JX0336. DR PIR; S21302; S21302. DR RefSeq; NP_001281261.1; NM_001294332.1. [P31040-2] DR RefSeq; NP_004159.2; NM_004168.3. [P31040-1] DR PDB; 6VAX; X-ray; 2.59 A; A/C=44-664. DR PDB; 8GS8; EM; 2.86 A; A=1-664. DR PDBsum; 6VAX; -. DR PDBsum; 8GS8; -. DR AlphaFoldDB; P31040; -. DR EMDB; EMD-34225; -. DR SMR; P31040; -. DR BioGRID; 112290; 390. DR ComplexPortal; CPX-561; Mitochondrial respiratory chain complex II. DR CORUM; P31040; -. DR DIP; DIP-45851N; -. DR IntAct; P31040; 208. DR MINT; P31040; -. DR STRING; 9606.ENSP00000264932; -. DR BindingDB; P31040; -. DR ChEMBL; CHEMBL5758; -. DR DrugBank; DB04141; 2-Hexyloxy-6-Hydroxymethyl-Tetrahydro-Pyran-3,4,5-Triol. DR DrugBank; DB04657; Carboxin. DR DrugBank; DB00139; Succinic acid. DR DrugBank; DB04795; Thenoyltrifluoroacetone. DR DrugBank; DB09270; Ubidecarenone. DR DrugBank; DB08689; Ubiquinone Q1. DR TCDB; 3.D.10.1.7; the prokaryotic succinate dehydrogenase (sdh) family. DR GlyGen; P31040; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P31040; -. DR MetOSite; P31040; -. DR PhosphoSitePlus; P31040; -. DR SwissPalm; P31040; -. DR BioMuta; SDHA; -. DR DMDM; 1169337; -. DR REPRODUCTION-2DPAGE; IPI00305166; -. DR CPTAC; CPTAC-440; -. DR EPD; P31040; -. DR jPOST; P31040; -. DR MassIVE; P31040; -. DR MaxQB; P31040; -. DR PaxDb; 9606-ENSP00000264932; -. DR PeptideAtlas; P31040; -. DR ProteomicsDB; 19239; -. DR ProteomicsDB; 54758; -. [P31040-1] DR Pumba; P31040; -. DR TopDownProteomics; P31040-1; -. [P31040-1] DR Antibodypedia; 22208; 464 antibodies from 34 providers. DR DNASU; 6389; -. DR Ensembl; ENST00000264932.11; ENSP00000264932.6; ENSG00000073578.18. [P31040-1] DR Ensembl; ENST00000510361.5; ENSP00000427703.1; ENSG00000073578.18. [P31040-2] DR GeneID; 6389; -. DR KEGG; hsa:6389; -. DR MANE-Select; ENST00000264932.11; ENSP00000264932.6; NM_004168.4; NP_004159.2. DR UCSC; uc003jao.5; human. [P31040-1] DR AGR; HGNC:10680; -. DR CTD; 6389; -. DR DisGeNET; 6389; -. DR GeneCards; SDHA; -. DR GeneReviews; SDHA; -. DR HGNC; HGNC:10680; SDHA. DR HPA; ENSG00000073578; Tissue enhanced (heart muscle, skeletal muscle). DR MalaCards; SDHA; -. DR MIM; 252011; phenotype. DR MIM; 256000; phenotype. DR MIM; 600857; gene. DR MIM; 613642; phenotype. DR MIM; 614165; phenotype. DR MIM; 619259; phenotype. DR neXtProt; NX_P31040; -. DR OpenTargets; ENSG00000073578; -. DR Orphanet; 154; Familial isolated dilated cardiomyopathy. DR Orphanet; 44890; Gastrointestinal stromal tumor. DR Orphanet; 29072; Hereditary pheochromocytoma-paraganglioma. DR Orphanet; 3208; Isolated succinate-CoQ reductase deficiency. DR PharmGKB; PA35605; -. DR VEuPathDB; HostDB:ENSG00000073578; -. DR eggNOG; KOG2403; Eukaryota. DR GeneTree; ENSGT00910000144277; -. DR InParanoid; P31040; -. DR OMA; SAIMRAY; -. DR OrthoDB; 551958at2759; -. DR PhylomeDB; P31040; -. DR TreeFam; TF300763; -. DR BioCyc; MetaCyc:ENSG00000073578-MONOMER; -. DR PathwayCommons; P31040; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-71403; Citric acid cycle (TCA cycle). DR SignaLink; P31040; -. DR SIGNOR; P31040; -. DR UniPathway; UPA00223; UER01006. DR BioGRID-ORCS; 6389; 240 hits in 1171 CRISPR screens. DR ChiTaRS; SDHA; human. DR GeneWiki; SDHA; -. DR GenomeRNAi; 6389; -. DR Pharos; P31040; Tbio. DR PRO; PR:P31040; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P31040; Protein. DR Bgee; ENSG00000073578; Expressed in apex of heart and 97 other cell types or tissues. DR ExpressionAtlas; P31040; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB. DR GO; GO:0005749; C:mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone); ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0009055; F:electron transfer activity; IBA:GO_Central. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central. DR GO; GO:0102040; F:fumarate reductase (menaquinone); IEA:UniProtKB-EC. DR GO; GO:0008177; F:succinate dehydrogenase (ubiquinone) activity; IMP:UniProtKB. DR GO; GO:0006121; P:mitochondrial electron transport, succinate to ubiquinone; IBA:GO_Central. DR GO; GO:0007399; P:nervous system development; IMP:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR GO; GO:0022904; P:respiratory electron transport chain; IDA:UniProtKB. DR GO; GO:0006105; P:succinate metabolic process; IDA:UniProtKB. DR GO; GO:0006099; P:tricarboxylic acid cycle; TAS:UniProtKB. DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 1. DR Gene3D; 1.20.58.100; Fumarate reductase/succinate dehydrogenase flavoprotein-like, C-terminal domain; 1. DR Gene3D; 4.10.80.40; succinate dehydrogenase protein domain; 1. DR Gene3D; 3.90.700.10; Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain; 1. DR InterPro; IPR003953; FAD-binding_2. DR InterPro; IPR036188; FAD/NAD-bd_sf. DR InterPro; IPR003952; FRD_SDH_FAD_BS. DR InterPro; IPR037099; Fum_R/Succ_DH_flav-like_C_sf. DR InterPro; IPR015939; Fum_Rdtase/Succ_DH_flav-like_C. DR InterPro; IPR030664; SdhA/FrdA/AprA. DR InterPro; IPR027477; Succ_DH/fumarate_Rdtase_cat_sf. DR InterPro; IPR011281; Succ_DH_flav_su_fwd. DR InterPro; IPR014006; Succ_Dhase_FrdA_Gneg. DR NCBIfam; TIGR01816; sdhA_forward; 1. DR NCBIfam; TIGR01812; sdhA_frdA_Gneg; 1. DR PANTHER; PTHR11632; SUCCINATE DEHYDROGENASE 2 FLAVOPROTEIN SUBUNIT; 1. DR PANTHER; PTHR11632:SF51; SUCCINATE DEHYDROGENASE [UBIQUINONE] FLAVOPROTEIN SUBUNIT, MITOCHONDRIAL; 1. DR Pfam; PF00890; FAD_binding_2; 1. DR Pfam; PF02910; Succ_DH_flav_C; 1. DR PIRSF; PIRSF000171; SDHA_APRA_LASPO; 1. DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1. DR SUPFAM; SSF46977; Succinate dehydrogenase/fumarate reductase flavoprotein C-terminal domain; 1. DR SUPFAM; SSF56425; Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain; 1. DR PROSITE; PS00504; FRD_SDH_FAD_BINDING; 1. DR Genevisible; P31040; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cardiomyopathy; KW Direct protein sequencing; Disease variant; Electron transport; FAD; KW Flavoprotein; Leigh syndrome; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Neurodegeneration; Oxidoreductase; KW Phosphoprotein; Primary mitochondrial disease; Reference proteome; KW Transit peptide; Transport; Tricarboxylic acid cycle; Tumor suppressor. FT TRANSIT 1..42 FT /note="Mitochondrion" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT CHAIN 43..664 FT /note="Succinate dehydrogenase [ubiquinone] flavoprotein FT subunit, mitochondrial" FT /id="PRO_0000010335" FT ACT_SITE 340 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:Q9YHT1" FT BINDING 68..73 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT BINDING 91..106 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT BINDING 275 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT BINDING 296 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT BINDING 308 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT BINDING 407 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT BINDING 440 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT BINDING 451 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT BINDING 456..457 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT MOD_RES 99 FT /note="Tele-8alpha-FAD histidine" FT /evidence="ECO:0000250|UniProtKB:Q0QF01" FT MOD_RES 167 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 179 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 179 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 182 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 215 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:22823520" FT MOD_RES 250 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 250 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 335 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 335 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 480 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 485 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 485 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 498 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 498 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 517 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 538 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 538 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 541 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 547 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 547 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 550 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 598 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 608 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 615 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 624 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 636 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT MOD_RES 647 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q8K2B3" FT VAR_SEQ 105..152 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055077" FT VAR_SEQ 126..270 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_055078" FT VARIANT 33 FT /note="F -> V (in dbSNP:rs1061518)" FT /id="VAR_049214" FT VARIANT 38 FT /note="D -> V (in dbSNP:rs34635677)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_049215" FT VARIANT 189 FT /note="C -> G (in LS; decrease in succinate dehydrogenase FT activity)" FT /evidence="ECO:0000269|PubMed:24781757" FT /id="VAR_074022" FT VARIANT 240 FT /note="E -> Q (in dbSNP:rs1041946)" FT /id="VAR_049216" FT VARIANT 333 FT /note="V -> I (in dbSNP:rs1062468)" FT /id="VAR_059307" FT VARIANT 451 FT /note="R -> C (in NDAXOA; dbSNP:rs1553999752)" FT /evidence="ECO:0000269|PubMed:10976639, FT ECO:0000269|PubMed:27683074" FT /id="VAR_085584" FT VARIANT 508 FT /note="T -> I (in dbSNP:rs151266052)" FT /evidence="ECO:0000269|PubMed:22972948, FT ECO:0000269|PubMed:26642834" FT /id="VAR_085396" FT VARIANT 509 FT /note="S -> L (in MC2DN1; uncertain significance; FT dbSNP:rs397514541)" FT /evidence="ECO:0000269|PubMed:22972948, FT ECO:0000269|PubMed:26642834" FT /id="VAR_085397" FT VARIANT 524 FT /note="A -> V (in LS; dbSNP:rs137852767)" FT /evidence="ECO:0000269|PubMed:10746566" FT /id="VAR_016878" FT VARIANT 554 FT /note="R -> W (in LS; dbSNP:rs9809219)" FT /evidence="ECO:0000269|PubMed:7550341" FT /id="VAR_002449" FT VARIANT 555 FT /note="G -> E (in MC2DN1 and CMD1GG; dbSNP:rs137852768)" FT /evidence="ECO:0000269|PubMed:12794685, FT ECO:0000269|PubMed:20551992" FT /id="VAR_016879" FT VARIANT 589 FT /note="R -> W (in PPGL5; loss of activity; FT dbSNP:rs387906780)" FT /evidence="ECO:0000269|PubMed:20484225" FT /id="VAR_065975" FT VARIANT 629 FT /note="Y -> F (in dbSNP:rs6960)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:8142412, ECO:0000269|Ref.5" FT /id="VAR_071037" FT VARIANT 657 FT /note="V -> I (in dbSNP:rs6962)" FT /evidence="ECO:0000269|PubMed:8142412" FT /id="VAR_049217" FT CONFLICT 356 FT /note="G -> D (in Ref. 3; AAD51006)" FT /evidence="ECO:0000305" FT CONFLICT 398 FT /note="E -> D (in Ref. 3; AAD51006)" FT /evidence="ECO:0000305" FT CONFLICT 591 FT /note="A -> T (in Ref. 3; AAD51006)" FT /evidence="ECO:0000305" FT CONFLICT 596 FT /note="D -> G (in Ref. 3; AAD51006)" FT /evidence="ECO:0000305" FT CONFLICT 600 FT /note="R -> Q (in Ref. 3; AAD51006)" FT /evidence="ECO:0000305" FT CONFLICT 618 FT /note="F -> L (in Ref. 4; BAG58722)" FT /evidence="ECO:0000305" FT CONFLICT 640 FT /note="E -> G (in Ref. 3; AAD51006)" FT /evidence="ECO:0000305" FT STRAND 57..61 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 63..67 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 71..82 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 87..93 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 95..97 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 99..102 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 113..115 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 119..129 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 130..132 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 136..144 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 146..156 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 179..182 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 196..210 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 214..217 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 219..227 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 230..238 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 239..241 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 244..248 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 250..254 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 260..262 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 263..268 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 275..282 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 293..300 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 301..303 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 310..313 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 317..319 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 327..330 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 332..334 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 335..337 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 340..353 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 358..361 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 363..367 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 373..377 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 383..391 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 395..397 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 400..409 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 412..415 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 420..425 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 428..437 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 439..441 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 445..447 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 456..474 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 486..489 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 490..500 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 505..507 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 508..522 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 523..525 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 529..544 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 545..548 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 555..558 FT /evidence="ECO:0007829|PDB:6VAX" FT HELIX 560..584 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 594..596 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 618..620 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 624..630 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 632..634 FT /evidence="ECO:0007829|PDB:6VAX" FT STRAND 637..643 FT /evidence="ECO:0007829|PDB:6VAX" FT TURN 651..653 FT /evidence="ECO:0007829|PDB:6VAX" SQ SEQUENCE 664 AA; 72692 MW; 180B664E3FFD0B34 CRC64; MSGVRGLSRL LSARRLALAK AWPTVLQTGT RGFHFTVDGN KRASAKVSDS ISAQYPVVDH EFDAVVVGAG GAGLRAAFGL SEAGFNTACV TKLFPTRSHT VAAQGGINAA LGNMEEDNWR WHFYDTVKGS DWLGDQDAIH YMTEQAPAAV VELENYGMPF SRTEDGKIYQ RAFGGQSLKF GKGGQAHRCC CVADRTGHSL LHTLYGRSLR YDTSYFVEYF ALDLLMENGE CRGVIALCIE DGSIHRIRAK NTVVATGGYG RTYFSCTSAH TSTGDGTAMI TRAGLPCQDL EFVQFHPTGI YGAGCLITEG CRGEGGILIN SQGERFMERY APVAKDLASR DVVSRSMTLE IREGRGCGPE KDHVYLQLHH LPPEQLATRL PGISETAMIF AGVDVTKEPI PVLPTVHYNM GGIPTNYKGQ VLRHVNGQDQ IVPGLYACGE AACASVHGAN RLGANSLLDL VVFGRACALS IEESCRPGDK VPPIKPNAGE ESVMNLDKLR FADGSIRTSE LRLSMQKSMQ NHAAVFRVGS VLQEGCGKIS KLYGDLKHLK TFDRGMVWNT DLVETLELQN LMLCALQTIY GAEARKESRG AHAREDYKVR IDEYDYSKPI QGQQKKPFEE HWRKHTLSYV DVGTGKVTLE YRPVIDKTLN EADCATVPPA IRSY //