SUCLG1

Succinyl-CoA ligase [GDP-forming] subunit alpha, mitochondrial is an enzyme that in humans is encoded by the SUCLG1 gene.^[5][6]

SUCLG1
Identifiers
Aliases	SUCLG1, GALPHA, MTDPS9, SUCLA1, succinate-CoA ligase alpha subunit, succinate-CoA ligase GDP/ADP-forming subunit alpha
External IDs	OMIM: 611224; MGI: 1927234; HomoloGene: 55785; GeneCards: SUCLG1; OMA:SUCLG1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p11.2 Start 84,423,528 bp[1] End 84,460,045 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 C1 Start 73,225,365 bp[2] End 73,253,894 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in kidney tubule glomerulus metanephric glomerulus renal medulla jejunal mucosa duodenum mucosa of transverse colon right ventricle mucosa of sigmoid colon apex of heart Top expressed in interventricular septum digastric muscle myocardium of ventricle brown adipose tissue plantaris muscle right kidney extensor digitorum longus muscle sternocleidomastoid muscle extraocular muscle vastus lateralis muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding ligase activity catalytic activity RNA binding succinate-CoA ligase (ADP-forming) activity succinate-CoA ligase (GDP-forming) activity nucleoside diphosphate kinase activity GDP binding succinate-CoA ligase activity Cellular component plasma membrane mitochondrion mitochondrial inner membrane extracellular exosome cytosol mitochondrial matrix succinate-CoA ligase complex (GDP-forming) Biological process metabolism tricarboxylic acid cycle succinyl-CoA metabolic process succinate metabolic process nucleoside diphosphate phosphorylation nucleoside triphosphate biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8802 56451 Ensembl ENSG00000163541 ENSMUSG00000052738 UniProt P53597 Q9WUM5 RefSeq (mRNA) NM_003849 NM_019879 RefSeq (protein) NP_003840 NP_063932 Location (UCSC) Chr 2: 84.42 – 84.46 Mb Chr 6: 73.23 – 73.25 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[7]

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.^[8][9]

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.^[10] 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.^[9]

Interactive pathway map

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

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|alt=TCACycle_WP78 edit]]

TCACycle_WP78 edit

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