SDHA_DROME
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 03-AUG-2022, entry version 195.
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; 14.
DR DIP; DIP-19386N; -.
DR IntAct; Q94523; 3.
DR STRING; 7227.FBpp0085736; -.
DR PaxDb; Q94523; -.
DR PRIDE; Q94523; -.
DR EnsemblMetazoa; FBtr0086552; FBpp0085736; FBgn0261439.
DR EnsemblMetazoa; FBtr0086553; FBpp0085737; FBgn0261439.
DR EnsemblMetazoa; FBtr0086554; FBpp0085738; FBgn0261439.
DR GeneID; 37228; -.
DR KEGG; dme:Dmel_CG17246; -.
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; DPIPIQP; -.
DR OrthoDB; 606981at2759; -.
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 tissues.
DR Genevisible; Q94523; DM.
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:0008177; F:succinate dehydrogenase (ubiquinone) activity; ISS:FlyBase.
DR GO; GO:0000104; F:succinate dehydrogenase activity; IBA:GO_Central.
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; -; 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; 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 PANTHER; PTHR11632; PTHR11632; 1.
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 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
