SDHA

Protein identityUniProt · HPA

UniProt accession

P31040

Gene

SDHA

Ensembl

ENSG00000073578

Chromosome

5

Canonical length

664 aa

Protein class

Cancer-related genes, Citric acid cycle related proteins, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Transporters

Subcellular location

Nucleoli,Mitochondria

OverviewNCBI Gene

This gene encodes a major catalytic subunit of succinate-ubiquinone oxidoreductase, a complex of the mitochondrial respiratory chain. The complex is composed of four nuclear-encoded subunits and is localized in the mitochondrial inner membrane. Mutations in this gene have been associated with a form of mitochondrial respiratory chain deficiency known as Leigh Syndrome. A pseudogene has been identified on chromosome 3q29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

Canonical amino-acid sequenceUniProt

664 residues, UniProt reviewed canonical sequence.

>P31040|SDHA
     1  MSGVRGLSRL LSARRLALAK AWPTVLQTGT RGFHFTVDGN KRASAKVSDS ISAQYPVVDH
    61  EFDAVVVGAG GAGLRAAFGL SEAGFNTACV TKLFPTRSHT VAAQGGINAA LGNMEEDNWR
   121  WHFYDTVKGS DWLGDQDAIH YMTEQAPAAV VELENYGMPF SRTEDGKIYQ RAFGGQSLKF
   181  GKGGQAHRCC CVADRTGHSL LHTLYGRSLR YDTSYFVEYF ALDLLMENGE CRGVIALCIE
   241  DGSIHRIRAK NTVVATGGYG RTYFSCTSAH TSTGDGTAMI TRAGLPCQDL EFVQFHPTGI
   301  YGAGCLITEG CRGEGGILIN SQGERFMERY APVAKDLASR DVVSRSMTLE IREGRGCGPE
   361  KDHVYLQLHH LPPEQLATRL PGISETAMIF AGVDVTKEPI PVLPTVHYNM GGIPTNYKGQ
   421  VLRHVNGQDQ IVPGLYACGE AACASVHGAN RLGANSLLDL VVFGRACALS IEESCRPGDK
   481  VPPIKPNAGE ESVMNLDKLR FADGSIRTSE LRLSMQKSMQ NHAAVFRVGS VLQEGCGKIS
   541  KLYGDLKHLK TFDRGMVWNT DLVETLELQN LMLCALQTIY GAEARKESRG AHAREDYKVR
   601  IDEYDYSKPI QGQQKKPFEE HWRKHTLSYV DVGTGKVTLE YRPVIDKTLN EADCATVPPA
   661  IRSY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SDHA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

522 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SDHA.

Disease | AllUniProt

Conditions SDHA is implicated in, by any mechanism.

• Mitochondrial complex II deficiency, nuclear type 1 (MC2DN1) MIM:252011
• Leigh syndrome (LS) MIM:256000
• Cardiomyopathy, dilated, 1GG (CMD1GG) MIM:613642
• Pheochromocytoma/paraganglioma syndrome 5 (PPGL5) MIM:614165
• Neurodegeneration with ataxia and late-onset optic atrophy (NDAXOA) MIM:619259

Disease | GeneticClinVar

329 pathogenic / likely-pathogenic of 3,314 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pheochromocytoma/paraganglioma syndrome 5
• Mitochondrial complex II deficiency, nuclear type 1
• Hereditary cancer-predisposing syndrome
• Dilated cardiomyopathy 1GG
• Neurodegeneration with ataxia and late-onset optic atrophy

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.86

gnomAD pLI

0

gnomAD missense Z

0.74

DepMap mean gene effect

-0.22

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 10% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• mitochondrial electron transport, succinate to ubiquinone
• nervous system development
• proton motive force-driven mitochondrial ATP synthesis
• respiratory electron transport chain
• succinate metabolic process
• tricarboxylic acid cycle

Molecular functions

• electron transfer activity
• flavin adenine dinucleotide binding
• succinate dehydrogenase (quinone) activity

Cellular components

• mitochondrial inner membrane
• mitochondrial matrix
• mitochondrion
• nucleolus
• respiratory chain complex II (succinate dehydrogenase)

Protein domainsUniProt · Pfam · InterPro

• FAD/NAD(P)-binding domain superfamily
• Fumarate reductase/succinate dehydrogenase, FAD-binding site
• FAD-dependent oxidoreductase 2, FAD-binding domain
• Succinate dehydrogenase, flavoprotein subunit
• Succinate dehydrogenase/fumarate reductase, flavoprotein subunit
• Fumarate reductase/succinate dehydrogenase flavoprotein-like, C-terminal
• Succinate dehydrogenase/fumarate reductase flavoprotein, catalytic domain superfamily
• FAD-dependent oxidoreductase SdhA/FrdA/AprA
• Fumarate reductase/succinate dehydrogenase flavoprotein-like, C-terminal domain superfamily
• FAD binding domain
• Fumarate reductase flavoprotein C-term

KeywordsUniProt

• Acetylation
• Cardiomyopathy
• Electron transport
• FAD
• Flavoprotein
• Leigh syndrome
• Membrane
• Mitochondrion
• Mitochondrion inner membrane
• Neurodegeneration
• Oxidoreductase
• Phosphoprotein
• Primary mitochondrial disease
• Transit peptide
• Transport
• Tricarboxylic acid cycle
• Tumor suppressor

InteractionsUniProt · HPA

Protein binding partners of SDHA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• LACC1
• TRAP1
• FXN
• SDHAF4
• CFTR
• PTPN3
• SDHAF2
• SDHB