ID   SDHA_DROME              Reviewed;         661 AA.
AC   Q94523; A4UZP5; C7LA77; Q0E918; Q9I7G3;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   21-FEB-2001, sequence version 3.
DT   27-MAR-2024, entry version 202.
DE   RecName: Full=Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial;
DE            EC=1.3.5.1 {ECO:0000250|UniProtKB:P31040};
DE   AltName: Full=Flavoprotein subunit of complex II;
DE            Short=FP;
DE   AltName: Full=Succinyl coenzyme A synthetase flavoprotein subunit;
DE   Flags: Precursor;
GN   Name=SdhA; Synonyms=Scs-fp; ORFNames=CG17246;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Head;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Embryo;
RA   Carlson J.W., Booth B., Frise E., Park S., Wan K.H., Yu C., Celniker S.E.;
RL   Submitted (AUG-2009) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 6-527.
RC   TISSUE=Ovary;
RX   PubMed=10071211; DOI=10.1007/s004380050942;
RA   Caggese C., Ragone G., Perrini B., Moschetti R., de Pinto V., Caizzi R.,
RA   Barsanti P.;
RT   "Identification of nuclear genes encoding mitochondrial proteins: isolation
RT   of a collection of D. melanogaster cDNAs homologous to sequences in the
RT   Human Gene Index database.";
RL   Mol. Gen. Genet. 261:64-70(1999).
RN   [6]
RP   IDENTIFICATION.
RX   PubMed=15693940; DOI=10.1186/gb-2005-6-2-r11;
RA   Tripoli G., D'Elia D., Barsanti P., Caggese C.;
RT   "Comparison of the oxidative phosphorylation (OXPHOS) nuclear genes in the
RT   genomes of Drosophila melanogaster, Drosophila pseudoobscura and Anopheles
RT   gambiae.";
RL   Genome Biol. 6:RESEARCH11.1-RESEARCH11.17(2005).
RN   [7]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=18599508; DOI=10.1242/dev.020644;
RA   Mast J.D., Tomalty K.M., Vogel H., Clandinin T.R.;
RT   "Reactive oxygen species act remotely to cause synapse loss in a Drosophila
RT   model of developmental mitochondrial encephalopathy.";
RL   Development 135:2669-2679(2008).
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). Maintaining electron transport chain function
CC       is required to prevent neurodegenerative changes seen in both
CC       early- and late-onset disorders. {ECO:0000269|PubMed:18599508}.
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:0000250|UniProtKB:P31040};
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:0000250|UniProtKB:P31040}.
CC   -!- SUBUNIT: Component of complex II composed of four subunits: a
CC       flavoprotein (FP), an iron-sulfur protein (IP), and a cytochrome b
CC       composed of a large and a small subunit.
CC       {ECO:0000250|UniProtKB:Q0QF01}.
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   -!- DISRUPTION PHENOTYPE: Disruption of mitochondrial function has no
CC       effect on the initial stages of photoreceptor development (R cells
CC       develop normally, adopt the correct cell fates, innervate the
CC       appropriate synaptic partners, and assemble synapses normally).
CC       However, beginning around the time of eclosion, R cells degenerate,
CC       progressively losing expression of synaptic markers and undergoing
CC       extensive morphological changes. Synapse loss is caused by reactive
CC       oxygen species (ROS) production, not energy depletion, as photoreceptor
CC       ATP levels are normal. {ECO:0000269|PubMed:18599508}.
CC   -!- SIMILARITY: Belongs to the FAD-dependent oxidoreductase 2 family.
CC       FRD/SDH subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA70285.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AE013599; AAG22257.1; -; Genomic_DNA.
DR   EMBL; AE013599; AAN16127.1; -; Genomic_DNA.
DR   EMBL; AY051472; AAK92896.1; -; mRNA.
DR   EMBL; BT099627; ACU51771.1; -; mRNA.
DR   EMBL; Y09064; CAA70285.1; ALT_INIT; mRNA.
DR   RefSeq; NP_477210.1; NM_057862.5.
DR   RefSeq; NP_725881.1; NM_166343.3.
DR   RefSeq; NP_725882.1; NM_166344.3.
DR   AlphaFoldDB; Q94523; -.
DR   SMR; Q94523; -.
DR   BioGRID; 62892; 15.
DR   DIP; DIP-19386N; -.
DR   IntAct; Q94523; 5.
DR   STRING; 7227.FBpp0085737; -.
DR   PaxDb; 7227-FBpp0085736; -.
DR   EnsemblMetazoa; FBtr0086552; FBpp0085736; FBgn0261439.
DR   EnsemblMetazoa; FBtr0086553; FBpp0085737; FBgn0261439.
DR   EnsemblMetazoa; FBtr0086554; FBpp0085738; FBgn0261439.
DR   GeneID; 37228; -.
DR   KEGG; dme:Dmel_CG17246; -.
DR   AGR; FB:FBgn0261439; -.
DR   CTD; 6389; -.
DR   FlyBase; FBgn0261439; SdhA.
DR   VEuPathDB; VectorBase:FBgn0261439; -.
DR   eggNOG; KOG2403; Eukaryota.
DR   GeneTree; ENSGT00910000144277; -.
DR   HOGENOM; CLU_014312_6_1_1; -.
DR   InParanoid; Q94523; -.
DR   OMA; FHPTGIW; -.
DR   OrthoDB; 551958at2759; -.
DR   PhylomeDB; Q94523; -.
DR   Reactome; R-DME-71403; Citric acid cycle (TCA cycle).
DR   UniPathway; UPA00223; UER01006.
DR   BioGRID-ORCS; 37228; 0 hits in 3 CRISPR screens.
DR   ChiTaRS; SdhA; fly.
DR   GenomeRNAi; 37228; -.
DR   PRO; PR:Q94523; -.
DR   Proteomes; UP000000803; Chromosome 2R.
DR   Bgee; FBgn0261439; Expressed in adult hindgut (Drosophila) and 45 other cell types or tissues.
DR   GO; GO:0005749; C:mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone); IBA:GO_Central.
DR   GO; GO:0005739; C:mitochondrion; HDA:FlyBase.
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; ISS:FlyBase.
DR   GO; GO:0022900; P:electron transport chain; IMP:UniProtKB.
DR   GO; GO:0006121; P:mitochondrial electron transport, succinate to ubiquinone; IBA:GO_Central.
DR   GO; GO:0022904; P:respiratory electron transport chain; ISS:FlyBase.
DR   GO; GO:0006105; P:succinate metabolic process; ISS:FlyBase.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-UniPathway.
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; Q94523; DM.
PE   2: Evidence at transcript level;
KW   Electron transport; FAD; Flavoprotein; Membrane; Mitochondrion;
KW   Mitochondrion inner membrane; Oxidoreductase; Reference proteome;
KW   Transit peptide; Transport; Tricarboxylic acid cycle.
FT   TRANSIT         1..41
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           42..661
FT                   /note="Succinate dehydrogenase [ubiquinone] flavoprotein
FT                   subunit, mitochondrial"
FT                   /id="PRO_0000010340"
FT   ACT_SITE        337
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   BINDING         65..70
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   BINDING         88..103
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   BINDING         272
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   BINDING         293
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   BINDING         305
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   BINDING         404
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   BINDING         438
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   BINDING         449
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   BINDING         454..455
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   MOD_RES         96
FT                   /note="Tele-8alpha-FAD histidine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9YHT1"
FT   CONFLICT        207
FT                   /note="S -> N (in Ref. 5; CAA70285)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        251
FT                   /note="I -> L (in Ref. 5; CAA70285)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        503
FT                   /note="Q -> L (in Ref. 5; CAA70285)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        520
FT                   /note="H -> L (in Ref. 5; CAA70285)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   661 AA;  72343 MW;  301B578C7F765011 CRC64;
     MSGIMRVPSI LAKNAVASMQ RAAAVGVQRS YHITHGRQQA SAANPDKISK QYPVVDHAYD
     AIVVGAGGAG LRAAFGLVAE GFRTAVITKL FPTRSHTIAA QGGINAALGN MEEDDWKWHM
     YDTVKGSDWL GDQDAIHYMT REAPKAVIEL ENYGMPFSRT QDGKIYQRAF GGQSLKFGKG
     GQAHRCCAVA DRTGHSLLHT LYGQSLSYDC NYFVEYFALD LIFEDGECRG VLALNLEDGT
     LHRFRAKNTV IATGGYGRAF FSCTSAHTCT GDGTAMVARQ GLPSQDLEFV QFHPTGIYGA
     GCLITEGCRG EGGYLINGNG ERFMERYAPV AKDLASRDVV SRSMTIEIME GRGAGPEKDH
     VYLQLHHLPP KQLAERLPGI SETAMIFAGV DVTREPIPVL PTVHYNMGGV PTNYRGQVIT
     IDKDGKDVIV PGLYAAGEAA SSSVHGANRL GANSLLDLVV FGRACAKTIA ELNKPGAPAP
     TLKENAGEAS VANLDKLRHA NGQITTADLR LKMQKTMQHH AAVFRDGPIL QDGVNKMKEI
     YKQFKDIKVV DRSLIWNSDL VETLELQNLL ANAQMTIVSA EARKESRGAH AREDFKVRED
     EYDFSKPLDG QQKKPMDQHW RKHTLSWVCN DNGDITLDYR NVIDTTLDNE VSTVPPAIRS
     Y
//