SUCA_DROME
ID SUCA_DROME Reviewed; 328 AA.
AC Q94522; M9MRQ9; Q8SXM7; Q9VZM4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 16-JAN-2004, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Succinate--CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03222};
DE EC=6.2.1.4 {ECO:0000255|HAMAP-Rule:MF_03222};
DE EC=6.2.1.5 {ECO:0000255|HAMAP-Rule:MF_03222};
DE AltName: Full=Succinyl-CoA synthetase subunit alpha {ECO:0000255|HAMAP-Rule:MF_03222};
DE Short=SCS-alpha {ECO:0000255|HAMAP-Rule:MF_03222};
DE AltName: Full=Succinyl-coenzyme A synthetase alpha subunit 1 {ECO:0000312|FlyBase:FBgn0004888};
DE Flags: Precursor;
GN Name=Scsalpha1 {ECO:0000312|FlyBase:FBgn0004888};
GN Synonyms=Scsalpha {ECO:0000312|FlyBase:FBgn0004888};
GN ORFNames=CG1065 {ECO:0000312|FlyBase:FBgn0004888};
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=Embryo;
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 [MRNA] OF 1-110.
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 [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28017724; DOI=10.1016/j.bbrc.2016.12.105;
RA Quan X., Sato-Miyata Y., Tsuda M., Muramatsu K., Asano T., Takeo S.,
RA Aigaki T.;
RT "Deficiency of succinyl-CoA synthetase alpha subunit delays development,
RT impairs locomotor activity and reduces survival under starvation in
RT Drosophila.";
RL Biochem. Biophys. Res. Commun. 483:566-571(2017).
CC -!- FUNCTION: Succinyl-CoA synthetase functions in the citric acid cycle
CC (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of
CC either ATP or GTP and thus represents the only step of substrate-level
CC phosphorylation in the TCA. The alpha subunit of the enzyme binds the
CC substrates coenzyme A and phosphate, while succinate binding and
CC specificity for either ATP or GTP is provided by different beta
CC subunits. {ECO:0000255|HAMAP-Rule:MF_03222,
CC ECO:0000305|PubMed:28017724}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + CoA + succinate = ADP + phosphate + succinyl-CoA;
CC Xref=Rhea:RHEA:17661, ChEBI:CHEBI:30031, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57287, ChEBI:CHEBI:57292,
CC ChEBI:CHEBI:456216; EC=6.2.1.5; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03222};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CoA + GTP + succinate = GDP + phosphate + succinyl-CoA;
CC Xref=Rhea:RHEA:22120, ChEBI:CHEBI:30031, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57287, ChEBI:CHEBI:57292,
CC ChEBI:CHEBI:58189; EC=6.2.1.4; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03222};
CC -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; succinate
CC from succinyl-CoA (ligase route): step 1/1. {ECO:0000255|HAMAP-
CC Rule:MF_03222}.
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Different beta
CC subunits determine nucleotide specificity. Together with an ATP-
CC specific beta subunit, forms an ADP-forming succinyl-CoA synthetase (A-
CC SCS). Together with a GTP-specific beta subunit forms a GDP-forming
CC succinyl-CoA synthetase (G-SCS). {ECO:0000255|HAMAP-Rule:MF_03222}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03222}.
CC -!- DISRUPTION PHENOTYPE: Viable (PubMed:28017724). During development,
CC results in delayed egg eclosion, reduced glycogen levels and extension
CC of the third instar larval period but without change of the duration of
CC the pupal period or final size of organ (PubMed:28017724). In the
CC adult, results in defects in locomotor activity (PubMed:28017724).
CC Results in disregulation of both glycolysis and the citric acid cycle
CC (TCA) including accumulation of Succinyl-CoA and succinate, and
CC reduction of GABA (PubMed:28017724). {ECO:0000269|PubMed:28017724}.
CC -!- SIMILARITY: Belongs to the succinate/malate CoA ligase alpha subunit
CC family. {ECO:0000255|HAMAP-Rule:MF_03222}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE014296; AAF47796.2; -; Genomic_DNA.
DR EMBL; AE014296; ADV37481.1; -; Genomic_DNA.
DR EMBL; AY089549; AAL90287.1; -; mRNA.
DR EMBL; Y09067; CAA70288.1; -; mRNA.
DR RefSeq; NP_001189044.1; NM_001202115.2.
DR RefSeq; NP_523905.2; NM_079181.4.
DR AlphaFoldDB; Q94522; -.
DR SMR; Q94522; -.
DR BioGRID; 63937; 6.
DR IntAct; Q94522; 7.
DR STRING; 7227.FBpp0073010; -.
DR PaxDb; Q94522; -.
DR PRIDE; Q94522; -.
DR DNASU; 38447; -.
DR EnsemblMetazoa; FBtr0073151; FBpp0073010; FBgn0004888.
DR EnsemblMetazoa; FBtr0303096; FBpp0292215; FBgn0004888.
DR GeneID; 38447; -.
DR KEGG; dme:Dmel_CG1065; -.
DR CTD; 38447; -.
DR FlyBase; FBgn0004888; Scsalpha1.
DR VEuPathDB; VectorBase:FBgn0004888; -.
DR eggNOG; KOG1255; Eukaryota.
DR GeneTree; ENSGT00940000156351; -.
DR HOGENOM; CLU_052104_1_0_1; -.
DR InParanoid; Q94522; -.
DR OMA; VIICITE; -.
DR OrthoDB; 1247548at2759; -.
DR PhylomeDB; Q94522; -.
DR Reactome; R-DME-71403; Citric acid cycle (TCA cycle).
DR UniPathway; UPA00223; UER00999.
DR BioGRID-ORCS; 38447; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 38447; -.
DR PRO; PR:Q94522; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0004888; Expressed in eye disc (Drosophila) and 25 other tissues.
DR Genevisible; Q94522; DM.
DR GO; GO:0005739; C:mitochondrion; HDA:FlyBase.
DR GO; GO:0009361; C:succinate-CoA ligase complex (ADP-forming); IBA:GO_Central.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0004775; F:succinate-CoA ligase (ADP-forming) activity; IBA:GO_Central.
DR GO; GO:0004776; F:succinate-CoA ligase (GDP-forming) activity; IBA:GO_Central.
DR GO; GO:0004778; F:succinyl-CoA hydrolase activity; IMP:FlyBase.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IMP:FlyBase.
DR Gene3D; 3.40.50.261; -; 1.
DR HAMAP; MF_01988; Succ_CoA_alpha; 1.
DR InterPro; IPR017440; Cit_synth/succinyl-CoA_lig_AS.
DR InterPro; IPR033847; Citrt_syn/SCS-alpha_CS.
DR InterPro; IPR003781; CoA-bd.
DR InterPro; IPR005810; CoA_lig_alpha.
DR InterPro; IPR005811; CoA_ligase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR016102; Succinyl-CoA_synth-like.
DR Pfam; PF02629; CoA_binding; 1.
DR Pfam; PF00549; Ligase_CoA; 1.
DR PIRSF; PIRSF001553; SucCS_alpha; 1.
DR SMART; SM00881; CoA_binding; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52210; SSF52210; 1.
DR TIGRFAMs; TIGR01019; sucCoAalpha; 1.
DR PROSITE; PS01216; SUCCINYL_COA_LIG_1; 1.
DR PROSITE; PS00399; SUCCINYL_COA_LIG_2; 1.
PE 2: Evidence at transcript level;
KW Ligase; Mitochondrion; Nucleotide-binding; Reference proteome;
KW Transit peptide; Tricarboxylic acid cycle.
FT TRANSIT 1..21
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222"
FT CHAIN 22..328
FT /note="Succinate--CoA ligase [ADP/GDP-forming] subunit
FT alpha, mitochondrial"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222"
FT /id="PRO_0000033339"
FT ACT_SITE 281
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222"
FT BINDING 46..49
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222"
FT BINDING 72
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222"
FT BINDING 125..127
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222"
FT BINDING 189
FT /ligand="substrate"
FT /ligand_note="ligand shared with subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222"
SQ SEQUENCE 328 AA; 34389 MW; 8FBDF50AED51EB93 CRC64;
MAASMRALLK VRDGFVAGVR CNSQYNKTRG NLKLNGDSRV ICQGFTGKQG TFHSQQALEY
GTKLVGGISP KKGGTQHLGL PVFASVAEAK KATDPHATVI YVPPPGAAAA IIEALEAEIP
LIVCITEGVP QHDMVKVKHA LISQSKSRLV GPNCPGIIAP EQCKIGIMPG HIHKRGKIGV
VSRSGTLTYE AVHQTTEVGL GQTLCVGIGG DPFNGTDFID CLEVFLKDPE TKGIILIGEI
GGVAEEKAAD YLTEYNSGIK AKPVVSFIAG VSAPPGRRMG HAGAIISGGK GGANDKIAAL
EKAGVIVTRS PAKMGHELFK EMKRLELV
