SUCLG1

Identifiers

SUCLG1, GALPHA, MTDPS9, SUCLA1, succinate-CoA ligase alpha subunit

External IDs

MGI: 1927234 HomoloGene: 55785 GeneCards: SUCLG1

Gene ontology
Molecular function	• nucleotide binding • GTP binding • ligase activity • catalytic activity • succinate-CoA ligase (ADP-forming) activity • cofactor binding • poly(A) RNA binding • succinate-CoA ligase (GDP-forming) activity
Cellular component	• cytoplasm • cytosol • plasma membrane • mitochondrial matrix • mitochondrion • mitochondrial inner membrane • extracellular exosome
Biological process	• succinyl-CoA metabolic process • tricarboxylic acid cycle • succinate metabolic process • nucleoside triphosphate biosynthetic process • metabolic process
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

Entrez


8802


56451

Ensembl


ENSG00000163541


ENSMUSG00000052738

UniProt


P53597


Q9WUM5

RefSeq (mRNA)


NM_003849


NM_019879

RefSeq (protein)


NP_003840.2


NP_063932.2

Location (UCSC)

Chr 2: 84.42 – 84.46 Mb

Chr 6: 73.25 – 73.28 Mb

PubMed search

^[1]

^[2]

Wikidata

View/Edit Human

View/Edit Mouse

Succinyl-CoA ligase [GDP-forming] subunit alpha, mitochondrial is an enzyme that in humans is encoded by the SUCLG1 gene.^[3]^[4]

Structure

The enzyme encoded by SUCLG1 can exist in either a phosphorylated form or a dephosphorylated form. In the dephosphorylated structure, a phosphate ion works in coordination with a histidine residue in the active site and the two alpha helices, one contributed by each subunit of the alphabeta-dimer to stabilize the structure. One of the alpha helices contains amino acids, the modification of which result in conformational changes that accommodate either the bound phosphoryl group or the free phosphate ion.^[5]

Function

This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion.^[6]^[7]

Clinical significance

Succinate-CoA ligase deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in SUCLG1 lead to complete absence of SUCLG1 protein and are responsible for a very severe disorder with antenatal manifestations. Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein is found in fibroblasts by western blot analysis. This result is consistent with a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent.^[8] As mitochondrial DNA depletion in muscle is not a constant finding in SUCLG1 patients, diagnosis should not be based on it; additionally, it may be that alternative physiopathological mechanisms may be considered to explain the combined respiratory chain deficiency observed in these patients.^[7]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|{{{bSize}}}px|alt=TCA Cycle edit]]

TCA Cycle edit

↑ The interactive pathway map can be edited at WikiPathways: "TCACycle_WP78".

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ James M, Man NT, Edwards YH, Morris GE (Apr 1997). "The molecular basis for cross-reaction of an anti-dystrophin antibody with alpha-actinin". Biochimica et Biophysica Acta. 1360 (2): 169–76. doi:10.1016/s0925-4439(96)00076-2. PMID 9128182.
↑ "Entrez Gene: SUCLG1 succinate-CoA ligase, GDP-forming, alpha subunit".
↑ Fraser ME, James MN, Bridger WA, Wolodko WT (Jun 2000). "Phosphorylated and dephosphorylated structures of pig heart, GTP-specific succinyl-CoA synthetase". Journal of Molecular Biology. 299 (5): 1325–39. doi:10.1006/jmbi.2000.3807. PMID 10873456.
↑ Ostergaard E (Apr 2008). "Disorders caused by deficiency of succinate-CoA ligase". Journal of Inherited Metabolic Disease. 31 (2): 226–9. doi:10.1007/s10545-008-0828-7. PMID 18392745.
1 2 Valayannopoulos V, Haudry C, Serre V, Barth M, Boddaert N, Arnoux JB, Cormier-Daire V, Rio M, Rabier D, Vassault A, Munnich A, Bonnefont JP, de Lonlay P, Rötig A, Lebre AS (Jun 2010). "New SUCLG1 patients expanding the phenotypic spectrum of this rare cause of mild methylmalonic aciduria". Mitochondrion. 10 (4): 335–41. doi:10.1016/j.mito.2010.02.006. PMID 20197121.
↑ Rouzier C, Le Guédard-Méreuze S, Fragaki K, Serre V, Miro J, Tuffery-Giraud S, Chaussenot A, Bannwarth S, Caruba C, Ostergaard E, Pellissier JF, Richelme C, Espil C, Chabrol B, Paquis-Flucklinger V (Oct 2010). "The severity of phenotype linked to SUCLG1 mutations could be correlated with residual amount of SUCLG1 protein". Journal of Medical Genetics. 47 (10): 670–6. doi:10.1136/jmg.2009.073445. PMID 20693550.