SUCA_PIG
ID SUCA_PIG Reviewed; 346 AA.
AC O19069; O19068;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 2.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Succinate--CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03222, ECO:0000305|PubMed:9261120};
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, ECO:0000303|PubMed:9261120};
DE Short=SCS-alpha {ECO:0000255|HAMAP-Rule:MF_03222};
DE Flags: Precursor;
GN Name=SUCLG1 {ECO:0000255|HAMAP-Rule:MF_03222};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-291 (ISOFORM I).
RX PubMed=14681463; DOI=10.1093/nar/gkh037;
RA Uenishi H., Eguchi T., Suzuki K., Sawazaki T., Toki D., Shinkai H.,
RA Okumura N., Hamasima N., Awata T.;
RT "PEDE (Pig EST Data Explorer): construction of a database for ESTs derived
RT from porcine full-length cDNA libraries.";
RL Nucleic Acids Res. 32:D484-D488(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-346 (ISOFORMS I AND II), NUCLEOTIDE
RP SEQUENCE [GENOMIC DNA] OF 133-234, ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=9261120; DOI=10.1074/jbc.272.34.21151;
RA Ryan D.G., Lin T., Brownie E., Bridger W.A., Wolodko W.T.;
RT "Mutually exclusive splicing generates two distinct isoforms of pig heart
RT succinyl-CoA synthetase.";
RL J. Biol. Chem. 272:21151-21159(1997).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 38-346 IN COMPLEX WITH SUCLG2,
RP AND ACTIVE SITE.
RX PubMed=10873456; DOI=10.1006/jmbi.2000.3807;
RA Fraser M.E., James M.N., Bridger W.A., Wolodko W.T.;
RT "Phosphorylated and dephosphorylated structures of pig heart, GTP-specific
RT succinyl-CoA synthetase.";
RL J. Mol. Biol. 299:1325-1339(2000).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 43-346 IN COMPLEX WITH SUCLG2,
RP AND ACTIVE SITE.
RX PubMed=16481318; DOI=10.1074/jbc.m511785200;
RA Fraser M.E., Hayakawa K., Hume M.S., Ryan D.G., Brownie E.R.;
RT "Interactions of GTP with the ATP-grasp domain of GTP-specific succinyl-CoA
RT synthetase.";
RL J. Biol. Chem. 281:11058-11065(2006).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 42-346 IN COMPLEX WITH SUCLG2 AND
RP COENZYME A.
RX PubMed=26249701; DOI=10.1107/s2053230x15011188;
RA Huang J., Malhi M., Deneke J., Fraser M.E.;
RT "Structure of GTP-specific succinyl-CoA synthetase in complex with CoA.";
RL Acta Crystallogr. F Struct. Biol. Commun. 71:1067-1071(2015).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 42-346 IN COMPLEX WITH SUCLG2 AND
RP SUCCINATE, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=27487822; DOI=10.1107/s2059798316010044;
RA Huang J., Fraser M.E.;
RT "Structural basis for the binding of succinate to succinyl-CoA
RT synthetase.";
RL Acta Crystallogr. D 72:912-921(2016).
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 -!- 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, ECO:0000269|PubMed:27487822};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.76 mM for succinate {ECO:0000269|PubMed:27487822};
CC Vmax=5.99 umol/min/mg enzyme {ECO:0000269|PubMed:27487822};
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 the ATP-
CC specific beta subunit SUCLA2, forms an ADP-forming succinyl-CoA
CC synthetase (A-SCS). Together with the GTP-specific beta subunit SUCLG2
CC forms a GDP-forming succinyl-CoA synthetase (G-SCS).
CC {ECO:0000255|HAMAP-Rule:MF_03222, ECO:0000269|PubMed:10873456,
CC ECO:0000269|PubMed:16481318, ECO:0000269|PubMed:26249701,
CC ECO:0000269|PubMed:27487822}.
CC -!- INTERACTION:
CC O19069; P53590: SUCLG2; NbExp=2; IntAct=EBI-9024832, EBI-7317595;
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03222}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=I;
CC IsoId=O19069-2; Sequence=Displayed;
CC Name=II;
CC IsoId=O19069-1; Sequence=VSP_036394;
CC -!- TISSUE SPECIFICITY: Isoform I is expressed in all tissues examined:
CC liver, brain, heart, and skeletal muscle. Isoform II is expressed only
CC in heart and skeletal muscle. {ECO:0000269|PubMed:9261120}.
CC -!- SIMILARITY: Belongs to the succinate/malate CoA ligase alpha subunit
CC family. {ECO:0000255|HAMAP-Rule:MF_03222}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB94003.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAB94004.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BP167826; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF008432; AAB94001.1; -; Genomic_DNA.
DR EMBL; AF008430; AAB94001.1; JOINED; Genomic_DNA.
DR EMBL; AF008433; AAB94002.2; -; Genomic_DNA.
DR EMBL; AF008430; AAB94002.2; JOINED; Genomic_DNA.
DR EMBL; AF008431; AAB94002.2; JOINED; Genomic_DNA.
DR EMBL; AF008588; AAB94003.1; ALT_INIT; mRNA.
DR EMBL; AF008589; AAB94004.1; ALT_INIT; mRNA.
DR RefSeq; NP_999574.1; NM_214409.2.
DR PDB; 1EUC; X-ray; 2.10 A; A=38-346.
DR PDB; 1EUD; X-ray; 2.10 A; A=38-346.
DR PDB; 2FP4; X-ray; 2.08 A; A=43-346.
DR PDB; 2FPG; X-ray; 2.96 A; A=43-346.
DR PDB; 2FPI; X-ray; 2.70 A; A=43-346.
DR PDB; 2FPP; X-ray; 2.35 A; A=43-346.
DR PDB; 4XX0; X-ray; 2.10 A; A=42-346.
DR PDB; 5CAE; X-ray; 2.20 A; A=42-346.
DR PDB; 6XRU; X-ray; 1.40 A; A=42-346.
DR PDB; 7JFP; X-ray; 2.55 A; A=42-346.
DR PDB; 7JJ0; X-ray; 2.25 A; A/C=42-346.
DR PDB; 7JKR; X-ray; 2.64 A; A=42-346.
DR PDB; 7JMK; X-ray; 2.50 A; A/C=42-346.
DR PDBsum; 1EUC; -.
DR PDBsum; 1EUD; -.
DR PDBsum; 2FP4; -.
DR PDBsum; 2FPG; -.
DR PDBsum; 2FPI; -.
DR PDBsum; 2FPP; -.
DR PDBsum; 4XX0; -.
DR PDBsum; 5CAE; -.
DR PDBsum; 6XRU; -.
DR PDBsum; 7JFP; -.
DR PDBsum; 7JJ0; -.
DR PDBsum; 7JKR; -.
DR PDBsum; 7JMK; -.
DR AlphaFoldDB; O19069; -.
DR SMR; O19069; -.
DR BioGRID; 1149836; 1.
DR CORUM; O19069; -.
DR IntAct; O19069; 1.
DR MINT; O19069; -.
DR STRING; 9823.ENSSSCP00000008807; -.
DR PeptideAtlas; O19069; -.
DR PRIDE; O19069; -.
DR Ensembl; ENSSSCT00015106587; ENSSSCP00015044873; ENSSSCG00015078686. [O19069-1]
DR Ensembl; ENSSSCT00015106597; ENSSSCP00015044879; ENSSSCG00015078686. [O19069-2]
DR Ensembl; ENSSSCT00045056295; ENSSSCP00045039272; ENSSSCG00045032848. [O19069-1]
DR Ensembl; ENSSSCT00045056419; ENSSSCP00045039374; ENSSSCG00045032848. [O19069-2]
DR Ensembl; ENSSSCT00050038804; ENSSSCP00050016058; ENSSSCG00050028857. [O19069-1]
DR Ensembl; ENSSSCT00050038809; ENSSSCP00050016059; ENSSSCG00050028857. [O19069-2]
DR Ensembl; ENSSSCT00055051051; ENSSSCP00055040814; ENSSSCG00055025718. [O19069-1]
DR Ensembl; ENSSSCT00060053297; ENSSSCP00060022696; ENSSSCG00060039395. [O19069-2]
DR Ensembl; ENSSSCT00060053302; ENSSSCP00060022698; ENSSSCG00060039395. [O19069-1]
DR Ensembl; ENSSSCT00065045018; ENSSSCP00065019282; ENSSSCG00065033087. [O19069-1]
DR Ensembl; ENSSSCT00065045023; ENSSSCP00065019285; ENSSSCG00065033087. [O19069-2]
DR GeneID; 399539; -.
DR KEGG; ssc:399539; -.
DR CTD; 8802; -.
DR eggNOG; KOG1255; Eukaryota.
DR InParanoid; O19069; -.
DR OrthoDB; 1247548at2759; -.
DR BRENDA; 6.2.1.4; 6170.
DR SABIO-RK; O19069; -.
DR UniPathway; UPA00223; UER00999.
DR EvolutionaryTrace; O19069; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
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:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Ligase; Mitochondrion;
KW Nucleotide-binding; Reference proteome; Transit peptide;
KW Tricarboxylic acid cycle.
FT TRANSIT 1..34
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222"
FT CHAIN 35..346
FT /note="Succinate--CoA ligase [ADP/GDP-forming] subunit
FT alpha, mitochondrial"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222"
FT /id="PRO_0000033342"
FT ACT_SITE 299
FT /note="Tele-phosphohistidine intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222,
FT ECO:0000269|PubMed:10873456, ECO:0000269|PubMed:16481318"
FT BINDING 64..67
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222,
FT ECO:0000269|PubMed:26249701"
FT BINDING 90
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222,
FT ECO:0000269|PubMed:26249701"
FT BINDING 143..145
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222,
FT ECO:0000269|PubMed:26249701"
FT BINDING 207
FT /ligand="substrate"
FT /ligand_note="ligand shared with subunit beta"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03222,
FT ECO:0000269|PubMed:27487822"
FT MOD_RES 54
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P53597"
FT MOD_RES 57
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9WUM5"
FT MOD_RES 57
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9WUM5"
FT MOD_RES 66
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9WUM5"
FT MOD_RES 66
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9WUM5"
FT MOD_RES 105
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WUM5"
FT MOD_RES 338
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WUM5"
FT VAR_SEQ 178..196
FT /note="PGECKIGIMPGHIHKKGRI -> RFLRFAVYITSRVFTCTQQEEYRKIPLLF
FT GTRSIHM (in isoform II)"
FT /evidence="ECO:0000303|PubMed:9261120"
FT /id="VSP_036394"
FT CONFLICT 2..4
FT /note="TAA -> PAG (in Ref. 2; AAB94003/AAB94004)"
FT /evidence="ECO:0000305"
FT HELIX 43..50
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 57..61
FT /evidence="ECO:0007829|PDB:6XRU"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:6XRU"
FT HELIX 66..78
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 81..86
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:6XRU"
FT HELIX 104..111
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 115..118
FT /evidence="ECO:0007829|PDB:6XRU"
FT HELIX 122..134
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:6XRU"
FT HELIX 149..159
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:2FP4"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:6XRU"
FT TURN 178..180
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 181..186
FT /evidence="ECO:0007829|PDB:6XRU"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 193..201
FT /evidence="ECO:0007829|PDB:6XRU"
FT HELIX 203..215
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 220..225
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:2FP4"
FT HELIX 236..245
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 251..261
FT /evidence="ECO:0007829|PDB:6XRU"
FT HELIX 262..273
FT /evidence="ECO:0007829|PDB:6XRU"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:1EUC"
FT STRAND 282..287
FT /evidence="ECO:0007829|PDB:6XRU"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:7JFP"
FT HELIX 300..303
FT /evidence="ECO:0007829|PDB:7JJ0"
FT HELIX 311..320
FT /evidence="ECO:0007829|PDB:6XRU"
FT HELIX 329..331
FT /evidence="ECO:0007829|PDB:6XRU"
FT HELIX 332..342
FT /evidence="ECO:0007829|PDB:6XRU"
SQ SEQUENCE 346 AA; 36117 MW; C5ACA670C214C2D4 CRC64;
MTAALVAAPA AATMASGSSG LAAARLLSRS FLLQQNGIRH CSYTASRKHL YVDKNTKVIC
QGFTGKQGTF HSQQALEYGT NLVGGTTPGK GGKTHLGLPV FNTVKEAKEQ TGATASVIYV
PPPFAAAAIN EAIDAEVPLV VCITEGIPQQ DMVRVKHRLL RQGKTRLIGP NCPGVINPGE
CKIGIMPGHI HKKGRIGIVS RSGTLTYEAV HQTTQVGLGQ SLCVGIGGDP FNGTDFTDCL
EIFLNDPATE GIILIGEIGG NAEENAAEFL KQHNSGPKSK PVVSFIAGLT APPGRRMGHA
GAIIAGGKGG AKEKITALQS AGVVVSMSPA QLGTTIYKEF EKRKML
