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Information on EC 6.2.1.5 - succinate-CoA ligase (ADP-forming) and Organism(s) Homo sapiens and UniProt Accession Q9P2R7
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6.2.1.5 succinate-CoA ligase (ADP-forming)Specify your search results
Word Map
- 6.2.1.5
- mtdna
- suclg1
-
methylmalonic
-
aciduria
- dguok
-
encephalomyopathic
- c10orf2
- mimigardefordensis
- twinkle
-
c4-dicarboxylic
- thiokinase
-
faroe
-
gtp-forming
-
hepatocerebral
-
3,3'-dithiodipropionic
- molecular biology
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
sucla2, succd, a-scs, cg11963, scact, adp-forming succinyl-coa synthetase, scs-betaa, a-stk, succinyl-coa synthetase subunit alpha, succinyl-coa synthetase (adp-forming), 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
A-SCS
-
-
-
-
A-STK
-
-
-
-
A-SUCL
SCS-alpha
-
-
-
-
SCS-beta
-
-
-
-
SCS-betaA
-
-
-
-
STK
-
-
-
-
Succinate thiokinase
-
-
-
-
Succinic thiokinase
-
-
-
-
Succinyl coenzyme A synthetase
-
-
-
-
Succinyl coenzyme A synthetase (adenosine diphosphate-forming)
-
-
-
-
Succinyl-CoA synthetase
-
-
-
-
Succinyl-CoA synthetase (ADP-forming)
-
-
-
-
Synthetase, succinyl coenzyme A (adenosine diphosphate-forming)
-
-
-
-
VEG239
-
-
-
-
VEG63
-
-
-
-
Vegetative protein 239
-
-
-
-
Vegetative protein 63
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acid-thiol ligation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -, -, -, -, -, -, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
succinate:CoA ligase (ADP-forming)
-
CAS REGISTRY NUMBER
COMMENTARY
9080-33-5
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + succinate + CoA
ADP + phosphate + succinyl-CoA
the enzyme is part of the Krebs cycle
-
-
?
additional information
?
-
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
additional information
?
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
additional information
?
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
additional information
?
-
the enzyme beta-subunit binds strongly to wild-type erythroid-specific aminolevulinic acid synthase, but not to the mutants M567V and S568G, aminolevulinic acid synthase mutant R452C shows binding to the succinyl-CoA synthetase, but with reduced affinity and positive cooperativity for succinyl-CoA
-
-
?
additional information
?
-
-
deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion
-
-
?
additional information
?
-
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
additional information
?
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
additional information
?
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + succinate + CoA
ADP + phosphate + succinyl-CoA
the enzyme is part of the Krebs cycle
-
-
?
additional information
?
-
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
additional information
?
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
additional information
?
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
additional information
?
-
the enzyme beta-subunit binds strongly to wild-type erythroid-specific aminolevulinic acid synthase, but not to the mutants M567V and S568G, aminolevulinic acid synthase mutant R452C shows binding to the succinyl-CoA synthetase, but with reduced affinity and positive cooperativity for succinyl-CoA
-
-
?
additional information
?
-
-
deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion
-
-
?
additional information
?
-
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
additional information
?
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
additional information
?
-
succinate-CoA ligase catalyses the reversible conversion of succinyl-CoA and ADP or GDP to succinate and ATP or GTP, cf. GTP-specific succinate:CoA ligase, EC 6.2.1.4
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
-
the enzyme is preferably expressed in catabolic tissues
additional information
the enzyme is preferably expressed in catabolic tissues
additional information
the enzyme is preferably expressed in catabolic tissues
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
probable role of an aminolevulinic acid synthase ALAS2-succinyl-CoA synthetase complex in the regulation of erythroid heme biosynthesis
malfunction
physiological function
additional information
malfunction
in patients with enzyme mutations, muscle histology shows severe lipid accumulation, and a marked type I fibre predominance is found, with an increased variability in fibre diameter. mtDNA depletion in succinate-CoA ligase deficiency
malfunction
enzyme mutations cause the encephalomyopathic mitochondrial DNA depletion syndrome with methylmalonic aciduria
malfunction
enzyme mutations result in succinyl-CoA ligase (ATP-forming) or succinyl-CoA synthetase (ADP-forming) deficiency, a mitochondrial tricarboxylic acid cycle disorder
malfunction
-
knockdown of SUCLG2 by shRNA in both SUCLA2-related mitochondrial DNA depletion syndrome patient and control fibroblasts results in a significant decrease in mtDNA amount, decreased NDPK and cytochrome c oxidase activities, and a marked growth impairment, phenotype, overview
malfunction
in patients with enzyme mutations, muscle histology shows severe lipid accumulation, and a marked type I fibre predominance is found, with an increased variability in fibre diameter. mtDNA depletion in succinate-CoA ligase deficiency
malfunction
-
inhibition of the enzyme might influence the activity of nucleoside diphosphate kinase inducing an imbalance of nucleotides in the mitochondria and eventually mitochondrial DNA depletion. This may account for the potential liver failure associated with valproate therapy, reported in patients with deficiencies within the mitochondrial DNA replicase system such as polymerase gamma 1
physiological function
-
SUCLG2, to a higher degree than SUCLA2, EC 6.2.1.4, is crucial for mtDNA maintenance involving mitochondrial NDPK
physiological function
-
the enzme is bound to the nucleoside diphosphate kinase, which is responsible for the mitochondrial (deoxy)nucleotide synthesis
additional information
C-terminal mutations in the erythroid-specific aminolevulinic acid synthase gene ALAS2 cause loss of binding to the beta-subunit of succinyl-CoA synthetase, SUCLA2, resulting in reduced mitochondrial enzymatic activity and X-linked sideroblastic anemia
additional information
-
the GDP-dependent isozyme SUCLG2 can complement the SUCLA2-related mitochondrial DNA depletion syndrome, a result of mutations in the beta subunit of the ADP-dependent isoform SUCLA2, EC 6.2.1.4
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SUCB1_HUMAN
463
0
50317
Swiss-Prot
Mitochondrion (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
heterodimer
the enzyme is composed of an alpha subunit, encoded by SUCLG1, and a beta subunit, encoded by either SUCLA2 or SUCLG2. The alpha-subunit forms a heterodimer with either of its beta-subunits, resulting in an ADP-forming succinate-CoA ligase, EC 6.2.1.5, and a GDP-forming succinate-CoA ligase, EC 6.2.1.4, respectively
heterodimer
the enzyme is composed of an alpha subunit, encoded by SUCLG1, and a beta subunit, encoded by either SUCLA2 or SUCLG2. The alpha-subunit forms a heterodimer with either of its beta-subunits, resulting in an ADP-forming succinate-CoA ligase, EC 6.2.1.5, and a GDP-forming succinate-CoA ligase, EC 6.2.1.4, respectively
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A103D
the mutation is associated with encephalomyopathic mitochondrial DNA depletion syndrome
A307V
the mutation is associated with succinyl-CoA ligase (ATP-forming) or succinyl-CoA synthetase (ADP-forming) deficiency
G424D
the mutation is associated with encephalomyopathic mitochondrial DNA depletion syndrome
I402Y
the mutation is associated with encephalomyopathic mitochondrial DNA depletion syndrome
M329V
the mutation is associated with succinyl-CoA ligase (ATP-forming) or succinyl-CoA synthetase (ADP-forming) deficiency
R284C
the mutation is associated with encephalomyopathic mitochondrial DNA depletion syndrome
R40T
the mutation is associated with encephalomyopathic mitochondrial DNA depletion syndrome
V370E
the mutation is associated with encephalomyopathic mitochondrial DNA depletion syndrome
additional information
additional information
-
naturally occuring mutations g.32720del43ins5 and IVS4+1G>A cause succinate-CoA ligase deficiency
additional information
naturally occuring mutations g.32720del43ins5 and IVS4+1G>A cause succinate-CoA ligase deficiency
additional information
naturally occuring mutations g.32720del43ins5 and IVS4+1G>A cause succinate-CoA ligase deficiency
additional information
-
patients with SUCLA2 mutations are expected to retain the activity of G-SUCL, and only the ATP production is expected to be compromised. In addition, in patients with SUCLA2 mutations, no liver symptoms are reported. The lactate level in patients with SUCLA2 mutations is normal or moderately elevated, phenotype, overview
additional information
patients with SUCLA2 mutations are expected to retain the activity of G-SUCL, and only the ATP production is expected to be compromised. In addition, in patients with SUCLA2 mutations, no liver symptoms are reported. The lactate level in patients with SUCLA2 mutations is normal or moderately elevated, phenotype, overview
additional information
patients with SUCLA2 mutations are expected to retain the activity of G-SUCL, and only the ATP production is expected to be compromised. In addition, in patients with SUCLA2 mutations, no liver symptoms are reported. The lactate level in patients with SUCLA2 mutations is normal or moderately elevated, phenotype, overview
additional information
-
the GDP-dependent isozyme SUCLG2 can complement the SUCLA2-related mitochondrial DNA depletion syndrome, a result of mutations in the beta subunit of the ADP-dependent isoform SUCLA2, EC 6.2.1.4
additional information
-
naturally occuring mutations g.32720del43ins5 and IVS4+1G>A cause succinate-CoA ligase deficiency
additional information
naturally occuring mutations g.32720del43ins5 and IVS4+1G>A cause succinate-CoA ligase deficiency
additional information
naturally occuring mutations g.32720del43ins5 and IVS4+1G>A cause succinate-CoA ligase deficiency
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant maltose-binding protein-tagged beta-subunit of succinyl-CoA synthetase, SUCLA2, from Escherichia coli strain Top10 by amylose affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of the maltose-binding protein-tagged beta-subunit of succinyl-CoA synthetase, SUCLA2, in Escherichia coli strain Top10
gene SUCLG2, DNA and amino acid sequence determination and analysis, semi quantitative RT-PCR expression analysis
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
molecular biology
the maltose-binding protein-tagged beta-subunit of succinyl-CoA synthetase, SUCLA2, bound to an amylose resin, is used as an affinity ligand to bind FPLC-purified wild-type and some mutant erythroid-specific aminolevulinic acid synthases, ALAS2
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Elpeleg, O.; Miller, C.; Hershkovitz, E.; Bitner-Glindzicz, M.; Bondi-Rubinstein, G.; Rahman, S.; Pagnamenta, A.; Eshhar, S.; Saada, A.
Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion
Am. J. Hum. Genet.
76
1081-1086
2005
Homo sapiens
Ostergaard, E.
Disorders caused by deficiency of succinate-CoA ligase
J. Inherit. Metab. Dis.
31
226-229
2008
Homo sapiens, Homo sapiens (P53597), Homo sapiens (Q9P2R7)
Miller, C.; Wang, L.; Ostergaard, E.; Dan, P.; Saada, A.
The interplay between SUCLA2, SUCLG2, and mitochondrial DNA depletion
Biochim. Biophys. Acta
1812
625-629
2011
Homo sapiens
Bishop, D.F.; Tchaikovskii, V.; Hoffbrand, A.V.; Fraser, M.E.; Margolis, S.
X-linked sideroblastic anemia due to carboxyl-terminal ALAS2 mutations that cause loss of binding to the beta-subunit of succinyl-CoA synthetase (SUCLA2)
J. Biol. Chem.
287
28943-28955
2012
Homo sapiens (Q9P2R7)
Luis, P.B.; Ruiter, J.; Ijlst, L.; de Almeida, I.T.; Duran, M.; Wanders, R.J.; Silva, M.F.
Valproyl-CoA inhibits the activity of ATP- and GTP-dependent succinate:CoA ligases
J. Inherit. Metab. Dis.
37
353-357
2013
Homo sapiens
Luis, P.; Ruiter, J.; IJlst, L.; De Almeida, I.; Duran, M.; Wanders, R.; Silva, M.
Valproyl-CoA inhibits the activity of ATP- and GTP-dependent succinate CoA ligases
J. Inherit. Metab. Dis.
37
353-357
2014
Homo sapiens
Carrozzo, R.; Verrigni, D.; Rasmussen, M.; de Coo, R.; Amartino, H.; Bianchi, M.; Buhas, D.; Mesli, S.; Naess, K.; Born, A.P.; Woldseth, B.; Prontera, P.; Batbayli, M.; Ravn, K.; Joensen, F.; Cordelli, D.M.; Santorelli, F.M.; Tulinius, M.; Darin, N.; Duno, M.; Jouvencel, P.; Burlina, A.; Stangoni, G.; , B.
Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1 phenotype and genotype correlations in 71 patients
J. Inherit. Metab. Dis.
39
243-252
2016
Homo sapiens (Q9P2R7), Homo sapiens
Huang, X.; Bedoyan, J.K.; Demirbas, D.; Harris, D.J.; Miron, A.; Edelheit, S.; Grahame, G.; DeBrosse, S.D.; Wong, L.J.; Hoppel, C.L.; Kerr, D.S.; Anselm, I.; Berry, G.T.
Succinyl-CoA synthetase (SUCLA2) deficiency in two siblings with impaired activity of other mitochondrial oxidative enzymes in skeletal muscle without mitochondrial DNA depletion
Mol. Genet. Metab.
120
213-222
2017
Homo sapiens (Q9P2R7)
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