SCOT1_PIG
ID SCOT1_PIG Reviewed; 520 AA.
AC Q29551; F1SMH7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial {ECO:0000303|PubMed:17718512};
DE Short=SCOT {ECO:0000303|PubMed:17718512, ECO:0000303|PubMed:20977214};
DE EC=2.8.3.5 {ECO:0000269|PubMed:11327867, ECO:0000269|PubMed:17718512};
DE AltName: Full=3-oxoacid CoA-transferase 1;
DE AltName: Full=Somatic-type succinyl-CoA:3-oxoacid CoA-transferase;
DE Short=SCOT-s;
DE AltName: Full=Succinate-coenzyme A transferase {ECO:0000303|PubMed:11327867};
DE AltName: Full=Succinyl-CoA:3-oxoacid CoA transferase {ECO:0000303|PubMed:20977214};
DE Flags: Precursor;
GN Name=OXCT1; Synonyms=OXCT, SCOT;
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 [MRNA], AND PROTEIN SEQUENCE OF 40-70 AND 296-305.
RC TISSUE=Heart;
RX PubMed=1730685; DOI=10.1016/s0021-9258(18)48381-0;
RA Lin T., Bridger W.A.;
RT "Sequence of a cDNA clone encoding pig heart mitochondrial CoA
RT transferase.";
RL J. Biol. Chem. 267:975-978(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Swine Genome Sequencing Consortium.;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP ACTIVE SITE.
RX PubMed=7915164; DOI=10.1002/pro.5560030613;
RA Rochet J.C., Bridger W.A.;
RT "Identification of glutamate 344 as the catalytic residue in the active
RT site of pig heart CoA transferase.";
RL Protein Sci. 3:975-981(1994).
RN [4]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11327867; DOI=10.1021/bi002169v;
RA Lloyd A.J., Shoolingin-Jordan P.M.;
RT "Dimeric pig heart succinate-coenzyme A transferase uses only one subunit
RT to support catalysis.";
RL Biochemistry 40:2455-2467(2001).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 40-520, AND SUBUNIT.
RC TISSUE=Heart;
RX PubMed=12463743; DOI=10.1021/bi020568f;
RA Bateman K.S., Brownie E.R., Wolodko W.T., Fraser M.E.;
RT "Structure of the mammalian CoA transferase from pig heart.";
RL Biochemistry 41:14455-14462(2002).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 40-520, AND SUBUNIT.
RC TISSUE=Heart;
RA Mitchell E.P., Lloyd A.J., Lewis G., Shoolingin-Jordan P.;
RT "Succinate:Coenzyme-A transferase deficiency: A structural view of
RT pathogenic mutations.";
RL Submitted (DEC-2002) to the PDB data bank.
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 40-520, AND SUBUNIT.
RC TISSUE=Heart;
RX PubMed=15388917; DOI=10.1107/s0907444904017974;
RA Coros A.M., Swenson L., Wolodko W.T., Fraser M.E.;
RT "Structure of the CoA transferase from pig heart to 1.7 A resolution.";
RL Acta Crystallogr. D 60:1717-1725(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 40-520 OF MUTANTS ALA/SER-67,
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, MUTAGENESIS OF CYS-67 AND CYS-235,
RP REACTION MECHANISM, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Heart;
RX PubMed=17718512; DOI=10.1021/bi700828h;
RA Tammam S.D., Rochet J.C., Fraser M.E.;
RT "Identification of the cysteine residue exposed by the conformational
RT change in pig heart succinyl-CoA:3-ketoacid coenzyme A transferase on
RT binding coenzyme A.";
RL Biochemistry 46:10852-10863(2007).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 40-520, AND SUBUNIT.
RC TISSUE=Heart;
RX PubMed=20606260; DOI=10.1107/s0907444910018366;
RA Coker S.F., Lloyd A.J., Mitchell E., Lewis G.R., Coker A.R.,
RA Shoolingin-Jordan P.M.;
RT "The high-resolution structure of pig heart succinyl-CoA:3-oxoacid coenzyme
RT A transferase.";
RL Acta Crystallogr. D 66:797-805(2010).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 40-517 IN COMPLEX WITH REACTION
RP INTERMEDIATE, FUNCTION, AND SUBUNIT.
RC TISSUE=Heart;
RX PubMed=20977214; DOI=10.1021/bi100659s;
RA Fraser M.E., Hayakawa K., Brown W.D.;
RT "Catalytic role of the conformational change in succinyl-CoA:3-oxoacid CoA
RT transferase on binding CoA.";
RL Biochemistry 49:10319-10328(2010).
CC -!- FUNCTION: Key enzyme for ketone body catabolism (By similarity).
CC Catalyzes the first, rate-limiting step of ketone body utilization in
CC extrahepatic tissues, by transferring coenzyme A (CoA) from a donor
CC thiolester species (succinyl-CoA) to an acceptor carboxylate
CC (acetoacetate), and produces acetoacetyl-CoA. Acetoacetyl-CoA is
CC further metabolized by acetoacetyl-CoA thiolase into two acetyl-CoA
CC molecules which enter the citric acid cycle for energy production
CC (PubMed:11327867, PubMed:17718512) (Probable). Forms a dimeric enzyme
CC where both of the subunits are able to form enzyme-CoA thiolester
CC intermediates, but only one subunit is competent to transfer the CoA
CC moiety to the acceptor carboxylate (3-oxo acid) and produce a new acyl-
CC CoA (PubMed:11327867). Formation of the enzyme-CoA intermediate
CC proceeds via an unstable anhydride species formed between the
CC carboxylate groups of the enzyme and substrate (PubMed:17718512).
CC {ECO:0000250|UniProtKB:P55809, ECO:0000269|PubMed:11327867,
CC ECO:0000269|PubMed:17718512, ECO:0000305|PubMed:20977214}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 3-oxo acid + succinyl-CoA = a 3-oxoacyl-CoA + succinate;
CC Xref=Rhea:RHEA:24564, ChEBI:CHEBI:30031, ChEBI:CHEBI:35973,
CC ChEBI:CHEBI:57292, ChEBI:CHEBI:90726; EC=2.8.3.5;
CC Evidence={ECO:0000269|PubMed:11327867, ECO:0000269|PubMed:17718512};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24565;
CC Evidence={ECO:0000269|PubMed:11327867, ECO:0000269|PubMed:17718512};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetoacetate + succinyl-CoA = acetoacetyl-CoA + succinate;
CC Xref=Rhea:RHEA:25480, ChEBI:CHEBI:13705, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:57286, ChEBI:CHEBI:57292; EC=2.8.3.5;
CC Evidence={ECO:0000269|PubMed:11327867, ECO:0000269|PubMed:17718512};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25481;
CC Evidence={ECO:0000269|PubMed:11327867, ECO:0000269|PubMed:17718512};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.20 mM for acetoacetyl-CoA {ECO:0000269|PubMed:17718512};
CC KM=20 mM for succinate {ECO:0000269|PubMed:17718512};
CC KM=6.5 mM for succinyl-CoA {ECO:0000269|PubMed:17718512};
CC KM=0.10 mM for acetoacetate {ECO:0000269|PubMed:17718512};
CC -!- PATHWAY: Ketone metabolism; succinyl-CoA degradation; acetoacetyl-CoA
CC from succinyl-CoA: step 1/1. {ECO:0000305|PubMed:11327867,
CC ECO:0000305|PubMed:17718512}.
CC -!- SUBUNIT: Homodimer (PubMed:12463743, PubMed:15388917, PubMed:17718512,
CC PubMed:20606260, PubMed:20977214, Ref.6, PubMed:11327867). Only one
CC subunit is competent to transfer the CoA moiety to the acceptor
CC carboxylate (3-oxo acid) (PubMed:11327867).
CC {ECO:0000269|PubMed:11327867, ECO:0000269|PubMed:12463743,
CC ECO:0000269|PubMed:15388917, ECO:0000269|PubMed:17718512,
CC ECO:0000269|PubMed:20606260, ECO:0000269|PubMed:20977214,
CC ECO:0000269|Ref.6}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:B2GV06}.
CC -!- SIMILARITY: Belongs to the 3-oxoacid CoA-transferase family.
CC {ECO:0000305}.
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DR EMBL; M80534; AAA31019.1; -; mRNA.
DR EMBL; CU993811; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FP017290; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A41771; A41771.
DR RefSeq; NP_999103.1; NM_213938.1.
DR PDB; 1M3E; X-ray; 2.50 A; A/B/C/D=40-520.
DR PDB; 1O9L; X-ray; 2.40 A; A/B/C/D=40-520.
DR PDB; 1OOY; X-ray; 1.70 A; A/B=40-520.
DR PDB; 1OOZ; X-ray; 2.10 A; A/B=40-520.
DR PDB; 1OPE; X-ray; 2.50 A; A/B=40-520.
DR PDB; 2NRB; X-ray; 2.00 A; A/B/C/D=40-520.
DR PDB; 2NRC; X-ray; 2.05 A; A/B/C/D=40-520.
DR PDB; 3K6M; X-ray; 1.50 A; A/B/C/D=40-520.
DR PDB; 3OXO; X-ray; 2.30 A; A/B/C/D/E/F/G/H=40-517.
DR PDBsum; 1M3E; -.
DR PDBsum; 1O9L; -.
DR PDBsum; 1OOY; -.
DR PDBsum; 1OOZ; -.
DR PDBsum; 1OPE; -.
DR PDBsum; 2NRB; -.
DR PDBsum; 2NRC; -.
DR PDBsum; 3K6M; -.
DR PDBsum; 3OXO; -.
DR AlphaFoldDB; Q29551; -.
DR SMR; Q29551; -.
DR STRING; 9823.ENSSSCP00000017870; -.
DR PaxDb; Q29551; -.
DR PeptideAtlas; Q29551; -.
DR PRIDE; Q29551; -.
DR Ensembl; ENSSSCT00000044789; ENSSSCP00000052664; ENSSSCG00000016863.
DR Ensembl; ENSSSCT00015084294; ENSSSCP00015034175; ENSSSCG00015062938.
DR Ensembl; ENSSSCT00025052144; ENSSSCP00025022246; ENSSSCG00025038332.
DR Ensembl; ENSSSCT00030078266; ENSSSCP00030035767; ENSSSCG00030056134.
DR Ensembl; ENSSSCT00040083222; ENSSSCP00040036256; ENSSSCG00040060882.
DR Ensembl; ENSSSCT00050075004; ENSSSCP00050032359; ENSSSCG00050054966.
DR Ensembl; ENSSSCT00055012324; ENSSSCP00055009717; ENSSSCG00055006211.
DR Ensembl; ENSSSCT00065089233; ENSSSCP00065039011; ENSSSCG00065065004.
DR Ensembl; ENSSSCT00070010135; ENSSSCP00070008322; ENSSSCG00070005220.
DR Ensembl; ENSSSCT00070010147; ENSSSCP00070008334; ENSSSCG00070005220.
DR GeneID; 396978; -.
DR KEGG; ssc:396978; -.
DR CTD; 5019; -.
DR VGNC; VGNC:91113; OXCT1.
DR eggNOG; KOG3822; Eukaryota.
DR GeneTree; ENSGT00390000009130; -.
DR HOGENOM; CLU_019942_2_0_1; -.
DR InParanoid; Q29551; -.
DR OMA; GTDYNKR; -.
DR OrthoDB; 460209at2759; -.
DR BRENDA; 2.8.3.5; 6170.
DR UniPathway; UPA00929; UER00894.
DR EvolutionaryTrace; Q29551; -.
DR Proteomes; UP000008227; Chromosome 16.
DR Proteomes; UP000314985; Chromosome 16.
DR Bgee; ENSSSCG00000016863; Expressed in heart left ventricle and 45 other tissues.
DR ExpressionAtlas; Q29551; baseline and differential.
DR Genevisible; Q29551; SS.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0008260; F:3-oxoacid CoA-transferase activity; IDA:UniProtKB.
DR GO; GO:0008410; F:CoA-transferase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0046950; P:cellular ketone body metabolic process; ISS:UniProtKB.
DR GO; GO:0046952; P:ketone body catabolic process; IEA:InterPro.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR012792; 3-oxoacid_CoA-transf_A.
DR InterPro; IPR012791; 3-oxoacid_CoA-transf_B.
DR InterPro; IPR014388; 3-oxoacid_CoA-transferase.
DR InterPro; IPR004165; CoA_trans_fam_I.
DR InterPro; IPR004164; CoA_transf_AS.
DR InterPro; IPR004163; CoA_transf_BS.
DR InterPro; IPR037171; NagB/RpiA_transferase-like.
DR PANTHER; PTHR13707; PTHR13707; 1.
DR Pfam; PF01144; CoA_trans; 2.
DR PIRSF; PIRSF000858; SCOT-t; 1.
DR SMART; SM00882; CoA_trans; 2.
DR SUPFAM; SSF100950; SSF100950; 2.
DR TIGRFAMs; TIGR02429; pcaI_scoA_fam; 1.
DR TIGRFAMs; TIGR02428; pcaJ_scoB_fam; 1.
DR PROSITE; PS01273; COA_TRANSF_1; 1.
DR PROSITE; PS01274; COA_TRANSF_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Lipid metabolism; Mitochondrion;
KW Phosphoprotein; Reference proteome; Transferase; Transit peptide.
FT TRANSIT 1..39
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1730685"
FT CHAIN 40..520
FT /note="Succinyl-CoA:3-ketoacid coenzyme A transferase 1,
FT mitochondrial"
FT /id="PRO_0000002415"
FT ACT_SITE 344
FT /note="5-glutamyl coenzyme A thioester intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10034,
FT ECO:0000269|PubMed:7915164"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55809"
FT MOD_RES 185
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D0K2"
FT MOD_RES 418
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D0K2"
FT MOD_RES 421
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D0K2"
FT MOD_RES 455
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9D0K2"
FT MUTAGEN 67
FT /note="C->A: Decreases KM for acetoacetyl-CoA 3-fold. No
FT effect on KM for acetoacetate, succinyl-CoA and succinate."
FT /evidence="ECO:0000269|PubMed:17718512"
FT MUTAGEN 67
FT /note="C->S: Decreases KM for acetoacetate and acetoacetyl-
FT CoA 2-fold. Increases KM for succinate 2-fold. Decreases KM
FT for succinyl-CoA nearly 4-fold. Strongly reduces catalytic
FT activity."
FT /evidence="ECO:0000269|PubMed:17718512"
FT MUTAGEN 235
FT /note="C->S: Similar specific activity to wild-type."
FT /evidence="ECO:0000269|PubMed:17718512"
FT CONFLICT 480
FT /note="S -> R (in Ref. 1; AAA31019)"
FT /evidence="ECO:0000305"
FT STRAND 41..44
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 46..50
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 71..80
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 100..104
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 108..114
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 120..127
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 130..135
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 138..149
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:3K6M"
FT TURN 159..162
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 164..167
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 171..174
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 178..183
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 195..201
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 205..216
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 237..249
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 302..309
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 317..321
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 325..329
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 339..343
FT /evidence="ECO:0007829|PDB:3K6M"
FT TURN 344..346
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 347..350
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 356..358
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 373..379
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 382..390
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 395..399
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 402..405
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:2NRC"
FT TURN 416..418
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 426..429
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 435..440
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 443..445
FT /evidence="ECO:0007829|PDB:2NRB"
FT HELIX 446..448
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 450..455
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 461..464
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 468..470
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 472..479
FT /evidence="ECO:0007829|PDB:3K6M"
FT TURN 480..482
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 483..489
FT /evidence="ECO:0007829|PDB:3K6M"
FT HELIX 495..500
FT /evidence="ECO:0007829|PDB:3K6M"
FT STRAND 502..504
FT /evidence="ECO:0007829|PDB:1M3E"
FT STRAND 507..514
FT /evidence="ECO:0007829|PDB:3K6M"
SQ SEQUENCE 520 AA; 56338 MW; 3DCFE430FE78C222 CRC64;
MAALTLLSSR LRLCASAYRS GGAWSQGCAG YFSTSTRRHT KFYTDAVEAV KDIPNGATVL
VGGFGLCGIP ENLIGALLKT GVKELTAVSN NAGVDNFGLG LLLQSKQIKR MISSYVGENA
EFERQYLAGE LEVELTPQGT LAERIRAGGA GVPAFYTSTG YGTLVQEGGS PIKYNKDGSI
AIASKPREVR EFNGQHFILE EAIRGDFALV KAWKADQAGN VTFRKSARNF NLPMCKAAET
TVVEVEEIVD IGSFAPEDIH IPKIYVHRLV KGEKYEKRIE RLSVRKEEDV KTRSGKLGDN
VRERIIKRAA LEFEDGMYAN LGIGIPLLAS NFISPNMTVH LQSENGILGL GPYPLQNEVD
ADLINAGKET VTVLPGASYF SSDESFAMIR GGHVNLTMLG AMQVSKYGDL ANWMIPGKLV
KGMGGAMDLV SSAKTKVVVT MEHSAKGNAH KIMEKCTLPL TGKQCVNRII TEKAVFDVDS
KKGLTLIELW EGLTVDDIKK STGCDFAVSP KLIPMQQVTT
