Recombinant Human Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial (SDHA), partial

Function

Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) (PubMed:10746566, PubMed:24781757). SDH also oxidizes malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate (By similarity). Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerized into keto-oxaloacetate (By similarity). Can act as a tumor suppressor (PubMed:20484225)

Subcellular Location

Mitochondrion inner membrane (Peripheral membrane protein)

Disease Association

Mitochondrial complex II deficiency, nuclear type 1 (MC2DN1) : A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. MC2DN1 inheritance is autosomal recessive. [The disease is caused by variants affecting the gene represented in this entry] | Leigh syndrome (LS) : An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. [The disease is caused by variants affecting the gene represented in this entry] | Cardiomyopathy, dilated, 1GG (CMD1GG) : A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. [The disease is caused by variants affecting the gene represented in this entry] | Pheochromocytoma/paraganglioma syndrome 5 (PPGL5) : A form of pheochromocytoma/paraganglioma syndrome, a tumor predisposition syndrome characterized by the development of neuroendocrine tumors, usually in adulthood. Pheochromocytomas are catecholamine-producing tumors that arise from chromaffin cells in the adrenal medulla. Paragangliomas develop from sympathetic paraganglia in the thorax, abdomen, and pelvis, as well as from parasympathetic paraganglia in the head and neck. PPGL5 inheritance is autosomal dominant. [The disease is caused by variants affecting the gene represented in this entry] | Neurodegeneration with ataxia and late-onset optic atrophy (NDAXOA) : An autosomal dominant disorder characterized by slowly progressive cerebellar and gait ataxia, optic atrophy, and myopathy or myalgia. Additional features can include cardiomyopathy, psychiatric disturbances, and peripheral sensory impairment. Disease onset is usually in mid-adulthood. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD (PubMed:37098072). Interacts with SDHAF2/SDH5; interaction is required for FAD attachment (PubMed:19628817, PubMed:32887801). Interacts with TRAP1 (PubMed:23747254). Interacts with LACC1 (PubMed:28593945)

Pathway

Carbohydrate metabolism; tricarboxylic acid cycle; fumarate from succinate (eukaryal route): step 1/1

• Hirawake H. et al. Human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the flavoprotein (Fp) subunit of liver mitochondria. — J. Biochem. (1994)
• Morris A.A.M. et al. The cDNA sequence of the flavoprotein subunit of human heart succinate dehydrogenase. — Biochim. Biophys. Acta (1994)
• Parfait B. et al. Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome. — Hum. Genet. (2000)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Totoki Y. et al. Homo sapiens protein coding cDNA. (MAR-)
• Schmutz J. et al. The DNA sequence and comparative analysis of human chromosome 5. — Nature (2004)
• Mural R.J. et al. PubMed: CI-5GBDQ6B103N1E (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)