SUCLG1

succinate-CoA ligase, alpha subunit
Identifiers
Aliases	SUCLG1, GALPHA, MTDPS9, SUCLA1
External IDs	MGI: 1927234 HomoloGene: 55785 GeneCards: 8802
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 • cellular metabolic process • small molecule metabolic process • nucleoside triphosphate biosynthetic process • metabolism 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
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.^[1][2]

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.^[3]

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.^[4][5]

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.^[6] 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.^[5]

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

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

References

1. 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.
2. "Entrez Gene: SUCLG1 succinate-CoA ligase, GDP-forming, alpha subunit".
3. 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.
4. 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.
5. 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.
6. 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.

Further reading

• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• 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.
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S (Sep 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
• Tsang HT, Connell JW, Brown SE, Thompson A, Reid E, Sanderson CM (Sep 2006). "A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex". Genomics 88 (3): 333–46. doi:10.1016/j.ygeno.2006.04.003. PMID 16730941.
• Ostergaard E, Christensen E, Kristensen E, Mogensen B, Duno M, Shoubridge EA, Wibrand F (Aug 2007). "Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion". American Journal of Human Genetics 81 (2): 383–7. doi:10.1086/519222. PMC 1950792. PMID 17668387.