SDHB

Protein identityUniProt · HPA

UniProt accession

P21912

Gene

SDHB

Ensembl

ENSG00000117118

Chromosome

1

Canonical length

280 aa

Protein class

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

Subcellular location

Nucleoplasm,Plasma membrane,Mitochondria

OverviewNCBI Gene

This tumor suppressor gene encodes the iron-sulfur protein subunit of the succinate dehydrogenase (SDH) enzyme complex which plays a critical role in mitochondria. The SDH enzyme complex is composed of four nuclear-encoded subunits. This enzyme complex converts succinate to fumarate which releases electrons as part of the citric acid cycle, and the enzyme complex additionally provides an attachment site for released electrons to be transferred to the oxidative phosphorylation pathway. The SDH enzyme complex plays a role in oxygen-related gene regulation through its conversion of succinate, which is an oxygen sensor that stabilizes the hypoxia-inducible factor 1 (HIF1) transcription factor. Sporadic and familial mutations in this gene result in paragangliomas, pheochromocytoma, and gastrointestinal stromal tumors, supporting a link between mitochondrial dysfunction and tumorigenesis. Mutations in this gene are also implicated in nuclear type 4 mitochondrial complex II deficiency. [provided by RefSeq, Jun 2022]

Canonical amino-acid sequenceUniProt

280 residues, UniProt reviewed canonical sequence.

>P21912|SDHB
     1  MAAVVALSLR RRLPATTLGG ACLQASRGAQ TAAATAPRIK KFAIYRWDPD KAGDKPHMQT
    61  YEVDLNKCGP MVLDALIKIK NEVDSTLTFR RSCREGICGS CAMNINGGNT LACTRRIDTN
   121  LNKVSKIYPL PHMYVIKDLV PDLSNFYAQY KSIEPYLKKK DESQEGKQQY LQSIEEREKL
   181  DGLYECILCA CCSTSCPSYW WNGDKYLGPA VLMQAYRWMI DSRDDFTEER LAKLQDPFSL
   241  YRCHTIMNCT RTCPKGLNPG KAIAEIKKMM ATYKEKKASV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SDHB 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)

0.34

Highest tissue expression

542 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SDHB.

Disease | AllUniProt

Conditions SDHB is implicated in, by any mechanism.

• Pheochromocytoma/paraganglioma syndrome 4 (PPGL4) MIM:115310
• Paraganglioma and gastric stromal sarcoma (PGGSS) MIM:606864
• Mitochondrial complex II deficiency, nuclear type 4 (MC2DN4) MIM:619224

Disease | GeneticClinVar

298 pathogenic / likely-pathogenic of 1,645 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pheochromocytoma/paraganglioma syndrome 4
• Gastrointestinal stromal tumor
• Pheochromocytoma
• Hereditary cancer-predisposing syndrome
• Hereditary pheochromocytoma and paraganglioma

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)

0.83

gnomAD pLI

0

gnomAD missense Z

-0.1

DepMap mean gene effect

-0.46

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

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

Molecular functions

• 2 iron, 2 sulfur cluster binding
• 3 iron, 4 sulfur cluster binding
• 4 iron, 4 sulfur cluster binding
• electron transfer activity
• metal ion binding
• succinate dehydrogenase (quinone) activity
• ubiquinone binding

Cellular components

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

Protein domainsUniProt · Pfam · InterPro

• 2Fe-2S ferredoxin-type iron-sulfur binding domain
• 2Fe-2S ferredoxin, iron-sulphur binding site
• Alpha-helical ferredoxin
• Beta-grasp domain superfamily
• 4Fe-4S ferredoxin-type, iron-sulphur binding domain
• 4Fe-4S ferredoxin, iron-sulphur binding, conserved site
• 2Fe-2S ferredoxin-like superfamily
• Succinate dehydrogenase/fumarate reductase iron-sulphur protein
• Succinate dehydogenase/fumarate reductase N-terminal
• Succinate Dehydrogenase/Fumarate Reductase Iron-Sulfur
• 2Fe-2S iron-sulfur cluster binding domain
• 4Fe-4S dicluster domain

KeywordsUniProt

• 2Fe-2S
• 4Fe-4S
• Acetylation
• Electron transport
• Host-virus interaction
• Iron
• Iron-sulfur
• Membrane
• Metal-binding
• Mitochondrion
• Mitochondrion inner membrane
• Oxidoreductase
• Primary mitochondrial disease
• Transit peptide
• Transport
• Tricarboxylic acid cycle
• 3Fe-4S

InteractionsUniProt · HPA

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

• SDHAF1
• FXN
• SDHA