GenomeNet

Database: UniProt/SWISS-PROT
Entry: SDHA_HUMAN
LinkDB: SDHA_HUMAN
Original site: SDHA_HUMAN 
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   13-FEB-2019, entry version 213.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=7798181;
RA   Hirawake H., Wang H., Kuramochi T., Kojima S., Kita K.;
RT   "Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning
RT   of 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
RP   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
RT   succinate 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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
RP   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.,
RA   Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA   Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA   Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA   Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA   Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA   Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA   Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA   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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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
RT   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
RT   the 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
RP   ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA   Walther T.C., 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 PGL5 TRP-589, AND CHARACTERIZATION OF VARIANT PGL5
RP   TRP-589.
RX   PubMed=20484225; DOI=10.1093/hmg/ddq206;
RA   Burnichon N., Briere J.J., Libe R., Vescovo L., Riviere J.,
RA   Tissier F., Jouanno E., Jeunemaitre X., Benit P., Tzagoloff A.,
RA   Rustin P., 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.,
RA   Buerckstuemmer T., 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
RT   of 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
RT   inhibiting 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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver 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.,
RA   Ayoub D., 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   VARIANT MT-C2D GLU-555.
RX   PubMed=12794685; DOI=10.1002/ajmg.a.10202;
RA   Van Coster R., Seneca S., Smet J., Van Hecke R., Gerlo E.,
RA   Devreese B., Van Beeumen J., Leroy J.G., De Meirleir L., Lissens W.;
RT   "Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa
RT   flavoprotein gene causes instability of the respiratory chain complex
RT   II.";
RL   Am. J. Med. Genet. A 120:13-18(2003).
RN   [21]
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   [22]
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.,
RA   Smeitink J.A., 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).
CC   -!- FUNCTION: Flavoprotein (FP) subunit of succinate dehydrogenase
CC       (SDH) that is involved in complex II of the mitochondrial electron
CC       transport chain and is responsible for transferring electrons from
CC       succinate to ubiquinone (coenzyme Q) (PubMed:24781757). Can act as
CC       a tumor suppressor (PubMed:20484225).
CC       {ECO:0000269|PubMed:20484225, 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;
CC       fumarate 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
CC       cytochrome b560 composed of SDHC and SDHD (By similarity).
CC       Interacts with SDHAF2/SDH5; interaction is required for FAD
CC       attachment (PubMed:19628817). Interacts with TRAP1
CC       (PubMed:23747254). {ECO:0000250|UniProtKB:Q0QF01,
CC       ECO:0000269|PubMed:19628817, ECO:0000269|PubMed:23747254}.
CC   -!- INTERACTION:
CC       P26045:PTPN3; NbExp=2; IntAct=EBI-1057265, EBI-1047946;
CC       Q9NX18:SDHAF2; NbExp=2; IntAct=EBI-1057265, EBI-713250;
CC       P21912:SDHB; NbExp=8; 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         Note=No experimental confirmation available.;
CC       Name=3;
CC         IsoId=P31040-3; Sequence=VSP_055078;
CC         Note=No experimental confirmation available.;
CC   -!- PTM: Phosphorylation at Tyr-215 is important for efficient
CC       electron transfer in complex II and the prevention of ROS
CC       generation. {ECO:0000269|PubMed:22823520}.
CC   -!- PTM: Acetylated. Deacetylated by SIRT3.
CC       {ECO:0000250|UniProtKB:Q8K2B3}.
CC   -!- DISEASE: Mitochondrial complex II deficiency (MT-C2D)
CC       [MIM:252011]: A disorder of the mitochondrial respiratory chain
CC       with heterogeneous clinical manifestations. Clinical features
CC       include psychomotor regression in infants, poor growth with lack
CC       of speech development, severe spastic quadriplegia, dystonia,
CC       progressive leukoencephalopathy, muscle weakness, exercise
CC       intolerance, cardiomyopathy. Some patients manifest Leigh syndrome
CC       or Kearns-Sayre syndrome. Note=The disease is caused by mutations
CC       affecting the gene represented in this entry.
CC       {ECO:0000269|PubMed:12794685}.
CC   -!- DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset
CC       progressive neurodegenerative disorder characterized by the
CC       presence of focal, bilateral lesions in one or more areas of the
CC       central nervous system including the brainstem, thalamus, basal
CC       ganglia, cerebellum and spinal cord. Clinical features depend on
CC       which areas of the central nervous system are involved and include
CC       subacute onset of psychomotor retardation, hypotonia, ataxia,
CC       weakness, vision loss, eye movement abnormalities, seizures, and
CC       dysphagia. {ECO:0000269|PubMed:10746566,
CC       ECO:0000269|PubMed:24781757, ECO:0000269|PubMed:7550341}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- DISEASE: Cardiomyopathy, dilated 1GG (CMD1GG) [MIM:613642]: A
CC       disorder characterized by ventricular dilation and impaired
CC       systolic function, resulting in congestive heart failure and
CC       arrhythmia. Patients are at risk of premature death.
CC       {ECO:0000269|PubMed:20551992}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Paragangliomas 5 (PGL5) [MIM:614165]: A neural crest
CC       tumor usually derived from the chromoreceptor tissue of a
CC       paraganglion. Paragangliomas can develop at various body sites,
CC       including the head, neck, thorax and abdomen. Most commonly, they
CC       are located in the head and neck region, specifically at the
CC       carotid bifurcation, the jugular foramen, the vagal nerve, and in
CC       the middle ear. {ECO:0000269|PubMed:20484225}. Note=The disease is
CC       caused by mutations 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=Translation N-terminally shortened.; 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="http://databases.lovd.nl/shared/genes/SDHA";
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   UniGene; Hs.440475; -.
DR   ProteinModelPortal; P31040; -.
DR   SMR; P31040; -.
DR   BioGrid; 112290; 232.
DR   ComplexPortal; CPX-561; Mitochondrial respiratory chain complex II.
DR   CORUM; P31040; -.
DR   DIP; DIP-45851N; -.
DR   IntAct; P31040; 160.
DR   MINT; P31040; -.
DR   STRING; 9606.ENSP00000264932; -.
DR   ChEMBL; CHEMBL5758; -.
DR   DrugBank; DB04657; Carboxin.
DR   DrugBank; DB00139; Succinic acid.
DR   DrugBank; DB04795; Thenoyltrifluoroacetone.
DR   DrugBank; DB08689; UBIQUINONE-1.
DR   iPTMnet; P31040; -.
DR   PhosphoSitePlus; P31040; -.
DR   SwissPalm; P31040; -.
DR   BioMuta; SDHA; -.
DR   DMDM; 1169337; -.
DR   REPRODUCTION-2DPAGE; IPI00305166; -.
DR   EPD; P31040; -.
DR   jPOST; P31040; -.
DR   MaxQB; P31040; -.
DR   PaxDb; P31040; -.
DR   PeptideAtlas; P31040; -.
DR   PRIDE; P31040; -.
DR   ProteomicsDB; 54758; -.
DR   TopDownProteomics; P31040-1; -. [P31040-1]
DR   DNASU; 6389; -.
DR   Ensembl; ENST00000264932; ENSP00000264932; ENSG00000073578. [P31040-1]
DR   Ensembl; ENST00000510361; ENSP00000427703; ENSG00000073578. [P31040-2]
DR   GeneID; 6389; -.
DR   KEGG; hsa:6389; -.
DR   UCSC; uc003jao.5; human. [P31040-1]
DR   CTD; 6389; -.
DR   DisGeNET; 6389; -.
DR   EuPathDB; HostDB:ENSG00000073578.16; -.
DR   GeneCards; SDHA; -.
DR   GeneReviews; SDHA; -.
DR   H-InvDB; HIX0120996; -.
DR   HGNC; HGNC:10680; SDHA.
DR   HPA; CAB034929; -.
DR   HPA; HPA041981; -.
DR   HPA; HPA064582; -.
DR   MalaCards; SDHA; -.
DR   MIM; 252011; phenotype.
DR   MIM; 256000; phenotype.
DR   MIM; 600857; gene.
DR   MIM; 613642; phenotype.
DR   MIM; 614165; 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   Orphanet; 255241; Leigh syndrome with leukodystrophy.
DR   PharmGKB; PA35605; -.
DR   eggNOG; KOG2403; Eukaryota.
DR   eggNOG; COG1053; LUCA.
DR   GeneTree; ENSGT00910000144277; -.
DR   HOGENOM; HOG000160475; -.
DR   HOVERGEN; HBG001461; -.
DR   InParanoid; P31040; -.
DR   KO; K00234; -.
DR   OMA; GDSPWEH; -.
DR   OrthoDB; 507784at2759; -.
DR   PhylomeDB; P31040; -.
DR   TreeFam; TF300763; -.
DR   BioCyc; MetaCyc:ENSG00000073578-MONOMER; -.
DR   Reactome; R-HSA-611105; Respiratory electron transport.
DR   Reactome; R-HSA-71403; Citric acid cycle (TCA cycle).
DR   SIGNOR; P31040; -.
DR   UniPathway; UPA00223; UER01006.
DR   ChiTaRS; SDHA; human.
DR   GeneWiki; SDHA; -.
DR   GenomeRNAi; 6389; -.
DR   PRO; PR:P31040; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   Bgee; ENSG00000073578; Expressed in 95 organ(s), highest expression level in apex of heart.
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:UniProtKB.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0045282; C:plasma membrane succinate dehydrogenase complex; IBA:GO_Central.
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:0008177; F:succinate dehydrogenase (ubiquinone) activity; IMP:UniProtKB.
DR   GO; GO:0000104; F:succinate dehydrogenase activity; IBA:GO_Central.
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:0055114; P:oxidation-reduction process; IDA:UniProtKB.
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; IBA:GO_Central.
DR   Gene3D; 3.50.50.60; -; 1.
DR   Gene3D; 3.90.700.10; -; 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; IPR027477; Succ_DH/fumarate_Rdtase_cat_sf.
DR   InterPro; IPR011281; Succ_DH_flav_su_fwd.
DR   InterPro; IPR014006; Succ_Dhase_FrdA_Gneg.
DR   Pfam; PF00890; FAD_binding_2; 1.
DR   Pfam; PF02910; Succ_DH_flav_C; 1.
DR   SUPFAM; SSF46977; SSF46977; 1.
DR   SUPFAM; SSF51905; SSF51905; 1.
DR   SUPFAM; SSF56425; SSF56425; 1.
DR   TIGRFAMs; TIGR01816; sdhA_forward; 1.
DR   TIGRFAMs; TIGR01812; sdhA_frdA_Gneg; 1.
DR   PROSITE; PS00504; FRD_SDH_FAD_BINDING; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Cardiomyopathy; Complete proteome;
KW   Direct protein sequencing; Disease mutation; Electron transport; FAD;
KW   Flavoprotein; Leigh syndrome; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Oxidoreductase; Phosphoprotein;
KW   Polymorphism; Primary mitochondrial disease; Reference proteome;
KW   Transit peptide; Transport; Tricarboxylic acid cycle;
KW   Tumor suppressor.
FT   TRANSIT       1     42       Mitochondrion.
FT                                {ECO:0000250|UniProtKB:Q0QF01}.
FT   CHAIN        43    664       Succinate dehydrogenase [ubiquinone]
FT                                flavoprotein subunit, mitochondrial.
FT                                /FTId=PRO_0000010335.
FT   NP_BIND      68     73       FAD. {ECO:0000250|UniProtKB:Q0QF01}.
FT   NP_BIND      91    106       FAD. {ECO:0000250|UniProtKB:Q0QF01}.
FT   NP_BIND     456    457       FAD. {ECO:0000250|UniProtKB:Q0QF01}.
FT   ACT_SITE    340    340       Proton acceptor.
FT                                {ECO:0000250|UniProtKB:Q9YHT1}.
FT   BINDING     275    275       FAD. {ECO:0000250|UniProtKB:Q0QF01}.
FT   BINDING     296    296       Substrate.
FT                                {ECO:0000250|UniProtKB:Q0QF01}.
FT   BINDING     308    308       Substrate.
FT                                {ECO:0000250|UniProtKB:Q0QF01}.
FT   BINDING     407    407       Substrate.
FT                                {ECO:0000250|UniProtKB:Q0QF01}.
FT   BINDING     440    440       FAD. {ECO:0000250|UniProtKB:Q0QF01}.
FT   BINDING     451    451       Substrate.
FT                                {ECO:0000250|UniProtKB:Q0QF01}.
FT   MOD_RES      99     99       Tele-8alpha-FAD histidine.
FT                                {ECO:0000250|UniProtKB:Q0QF01}.
FT   MOD_RES     167    167       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     179    179       N6-acetyllysine; alternate.
FT                                {ECO:0000244|PubMed:19608861}.
FT   MOD_RES     179    179       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     182    182       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     215    215       Phosphotyrosine; by SRC.
FT                                {ECO:0000269|PubMed:22823520}.
FT   MOD_RES     250    250       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     250    250       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     335    335       N6-acetyllysine; alternate.
FT                                {ECO:0000244|PubMed:19608861}.
FT   MOD_RES     335    335       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     480    480       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     485    485       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     485    485       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     498    498       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     498    498       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     517    517       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     538    538       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     538    538       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     541    541       N6-acetyllysine.
FT                                {ECO:0000244|PubMed:19608861}.
FT   MOD_RES     547    547       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     547    547       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     550    550       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     598    598       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     608    608       N6-acetyllysine.
FT                                {ECO:0000244|PubMed:19608861}.
FT   MOD_RES     615    615       N6-succinyllysine.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     624    624       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     636    636       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   MOD_RES     647    647       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q8K2B3}.
FT   VAR_SEQ     105    152       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_055077.
FT   VAR_SEQ     126    270       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_055078.
FT   VARIANT      33     33       F -> V (in dbSNP:rs1061518).
FT                                /FTId=VAR_049214.
FT   VARIANT      38     38       D -> V (in dbSNP:rs34635677).
FT                                {ECO:0000269|PubMed:14702039}.
FT                                /FTId=VAR_049215.
FT   VARIANT     189    189       C -> G (in LS; decrease in succinate
FT                                dehydrogenase activity).
FT                                {ECO:0000269|PubMed:24781757}.
FT                                /FTId=VAR_074022.
FT   VARIANT     240    240       E -> Q (in dbSNP:rs1041946).
FT                                /FTId=VAR_049216.
FT   VARIANT     333    333       V -> I (in dbSNP:rs1062468).
FT                                /FTId=VAR_059307.
FT   VARIANT     524    524       A -> V (in LS; dbSNP:rs137852767).
FT                                {ECO:0000269|PubMed:10746566}.
FT                                /FTId=VAR_016878.
FT   VARIANT     554    554       R -> W (in LS; dbSNP:rs9809219).
FT                                {ECO:0000269|PubMed:7550341}.
FT                                /FTId=VAR_002449.
FT   VARIANT     555    555       G -> E (in MT-C2D and CMD1GG;
FT                                dbSNP:rs137852768).
FT                                {ECO:0000269|PubMed:12794685,
FT                                ECO:0000269|PubMed:20551992}.
FT                                /FTId=VAR_016879.
FT   VARIANT     589    589       R -> W (in PGL5; loss of activity;
FT                                dbSNP:rs387906780).
FT                                {ECO:0000269|PubMed:20484225}.
FT                                /FTId=VAR_065975.
FT   VARIANT     629    629       Y -> F (in dbSNP:rs6960).
FT                                {ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:8142412,
FT                                ECO:0000269|Ref.5}.
FT                                /FTId=VAR_071037.
FT   VARIANT     657    657       V -> I (in dbSNP:rs6962).
FT                                {ECO:0000269|PubMed:8142412}.
FT                                /FTId=VAR_049217.
FT   CONFLICT    356    356       G -> D (in Ref. 3; AAD51006).
FT                                {ECO:0000305}.
FT   CONFLICT    398    398       E -> D (in Ref. 3; AAD51006).
FT                                {ECO:0000305}.
FT   CONFLICT    591    591       A -> T (in Ref. 3; AAD51006).
FT                                {ECO:0000305}.
FT   CONFLICT    596    596       D -> G (in Ref. 3; AAD51006).
FT                                {ECO:0000305}.
FT   CONFLICT    600    600       R -> Q (in Ref. 3; AAD51006).
FT                                {ECO:0000305}.
FT   CONFLICT    618    618       F -> L (in Ref. 4; BAG58722).
FT                                {ECO:0000305}.
FT   CONFLICT    640    640       E -> G (in Ref. 3; AAD51006).
FT                                {ECO:0000305}.
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
//
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