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";
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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 Genevisible; P31040; HS.
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.
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
//
