- SDHA
protein
Name=succinate dehydrogenase complex, subunit A, flavoprotein (Fp)
caption=
width=250px
HGNCid=10680
Symbol=SDHA
AltSymbols=SDH2
EntrezGene=6389
OMIM=600857
RefSeq=NM_004168
UniProt=Q59GW8
PDB=
ECnumber=
Chromosome=5
Arm=p
Band=15
LocusSupplementaryData=SDHA is an acronym for succinate dehydrogenase complex subunit A.
The term SDHA can refer to;
* The protein subunit itself.
* The gene that codes for this protein.The
succinate dehydrogenase (SDH) protein complex catalyzes the oxidation of succinate (succinate + ubiquinone => fumarate + ubiquinol). The SDHA subunit is connected to theSDHB subunit on the hydrophilic, catalytic end of the complex, and weighs 72.7 kDA. Electrons removed from succinate transfer to SDHA, transfer across SDHB to theSDHC /SDHD subunits on the hydrophobic end of the complex anchored in the mitochondrial membrane.Function of the SDHA Protein
The SDH complex is located on the inner membrane of the
mitochondria and participates in both theCitric Acid Cycle andRespiratory chain .SDHA acts as an intermediate in the basic SDH enzyme action:
# SDHA convertssuccinate tofumarate as part of theCitric Acid Cycle . This reaction also convertsFAD to FADH2.
# Electrons from the FADH2 are transferred to the SDHB subunit iron clusters [2Fe-2S] , [4Fe-4S] , [3Fe-4S] . This function is part of theRespiratory chain
# Finally the electrons are transferred to theUbiquinone (Q) pool via theSDHC /SDHD subunits.Gene that Codes for SDHA
The gene that codes for the SDHA protein is nuclear, even though the protein is located in the inner membrane of the
mitochondria . The location of the gene in humans is on the fifth chromosome at p15. Thegene is partitioned in 15exon s.The expressed protein has 664 amino acids.Role in Disease
Bi-allelic mutations (i.e. both copies of the gene are mutated) have been described in
Leigh syndrome .
Mutations in the SDHA subunit have a distinct pathology from mutations in the SDHB/SDHC/SDHD subunits; it is the only subunit to never have showntumor suppressor behaviour. Heterozygous carriers of an SDHA mutation do not developparaganglioma s as has been seen for mutations in the other subunits. This appears to be due to the expression of two similar SDHA genes (Types I and II) in the paraganglia systemBriere, JJ et al. 2005. "Human Molecular Genetics". Vol. 14 pg. 3263-3269.] . This would require the improbable event of inactivation of all four alleles to trigger a paraganglioma.References
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