O14521 · DHSD_HUMAN
- ProteinSuccinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial
- GeneSDHD
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids159 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Membrane-anchoring 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:10482792, PubMed:9533030).
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).
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).
Pathway
Carbohydrate metabolism; tricarboxylic acid cycle.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial envelope | |
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone) | |
Cellular Component | mitochondrion | |
Cellular Component | respiratory chain complex II | |
Molecular Function | electron transfer activity | |
Molecular Function | heme binding | |
Molecular Function | metal ion binding | |
Molecular Function | succinate dehydrogenase (quinone) activity | |
Molecular Function | ubiquinone binding | |
Biological Process | cellular response to hypoxia | |
Biological Process | mitochondrial electron transport, succinate to ubiquinone | |
Biological Process | proton motive force-driven mitochondrial ATP synthesis | |
Biological Process | regulation of catecholamine secretion | |
Biological Process | tricarboxylic acid cycle |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSuccinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial
- Short namesCybS
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO14521
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 57-63 | Mitochondrial matrix | ||||
Sequence: SGSKAAS | ||||||
Transmembrane | 64-85 | Helical | ||||
Sequence: LHWTSERVVSVLLLGLLPAAYL | ||||||
Topological domain | 86-90 | Mitochondrial intermembrane | ||||
Sequence: NPCSA | ||||||
Transmembrane | 91-111 | Helical | ||||
Sequence: MDYSLAAALTLHGHWGLGQVV | ||||||
Topological domain | 112-122 | Mitochondrial matrix | ||||
Sequence: TDYVHGDALQK | ||||||
Transmembrane | 123-144 | Helical | ||||
Sequence: AAKAGLLALSALTFAGLCYFNY | ||||||
Topological domain | 145-159 | Mitochondrial intermembrane | ||||
Sequence: HDVGICKAVAMLWKL |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Pheochromocytoma/paraganglioma syndrome 1 (PPGL1)
- Note
- DescriptionA 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. PPGL1 inheritance is autosomal dominant.
- See alsoMIM:168000
Natural variants in PPGL1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_010038 | 81 | P>L | in PPGL1; dbSNP:rs80338844 | |
VAR_010039 | 92 | D>Y | in PPGL1; dbSNP:rs80338845 | |
VAR_018519 | 93 | missing | in PPGL1; dbSNP:rs121908983 | |
VAR_010040 | 102 | H>L | in PPGL1; dbSNP:rs104894302 | |
VAR_017872 | 114 | Y>C | in PPGL1; dbSNP:rs104894304 | |
VAR_017873 | 139 | L>P | in PPGL1; dbSNP:rs80338847 | |
VAR_054385 | 148 | G>V | in PPGL1; dbSNP:rs1555187633 |
Paraganglioma and gastric stromal sarcoma (PGGSS)
- Note
- DescriptionGastrointestinal stromal tumors may be sporadic or inherited in an autosomal dominant manner, alone or as a component of a syndrome associated with other tumors, such as in the context of neurofibromatosis type 1 (NF1). Patients have both gastrointestinal stromal tumors and paragangliomas. Susceptibility to the tumors was inherited in an apparently autosomal dominant manner, with incomplete penetrance.
- See alsoMIM:606864
Mitochondrial complex II deficiency, nuclear type 3 (MC2DN3)
- Note
- DescriptionA form of mitochondrial complex II deficiency, a disorder with heterogeneous clinical manifestations. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. 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. MC2DN3 inheritance is autosomal recessive.
- See alsoMIM:619167
Natural variants in MC2DN3
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_074105 | 69 | E>K | in MC2DN3; results in impaired mitochondrial complex II assembly; results in impaired cellular respiration; dbSNP:rs202198133 | |
VAR_074106 | 92 | D>G | in MC2DN3; results in highly reduced protein expression; results in impaired cellular respiration; dbSNP:rs786205436 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_017870 | 12 | probable risk factor for pheochromocytoma, paraganglioma, intestinal carcinoid tumor and breast, renal and uterus carcinoma; increased manganese superoxide dismutase expression and increased reactive oxygen species; results in 1.9-fold increase in both AKT and MAPK expression; dbSNP:rs34677591 | |||
Sequence: G → S | ||||||
Natural variant | VAR_017871 | 50 | probable risk factor for paraganglioma, breast and thyroid carcinoma; may be involved in somatic Merkel cell carcinoma; increased manganese superoxide dismutase expression and increased reactive oxygen species; results in a 2.0-fold increase in AKT expression and a 1.7-fold increase in MAPK expression; dbSNP:rs11214077 | |||
Sequence: H → R | ||||||
Natural variant | VAR_074105 | 69 | in MC2DN3; results in impaired mitochondrial complex II assembly; results in impaired cellular respiration; dbSNP:rs202198133 | |||
Sequence: E → K | ||||||
Natural variant | VAR_010038 | 81 | in PPGL1; dbSNP:rs80338844 | |||
Sequence: P → L | ||||||
Natural variant | VAR_074106 | 92 | in MC2DN3; results in highly reduced protein expression; results in impaired cellular respiration; dbSNP:rs786205436 | |||
Sequence: D → G | ||||||
Natural variant | VAR_010039 | 92 | in PPGL1; dbSNP:rs80338845 | |||
Sequence: D → Y | ||||||
Natural variant | VAR_018519 | 93 | in PPGL1; dbSNP:rs121908983 | |||
Sequence: Missing | ||||||
Natural variant | VAR_010040 | 102 | in PPGL1; dbSNP:rs104894302 | |||
Sequence: H → L | ||||||
Natural variant | VAR_017872 | 114 | in PPGL1; dbSNP:rs104894304 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_017873 | 139 | in PPGL1; dbSNP:rs80338847 | |||
Sequence: L → P | ||||||
Natural variant | VAR_054384 | 145 | found in an individual with features of Cowden syndrome; uncertain significance; increased manganese superoxide dismutase expression and normal reactive oxygen species; no change in AKT expression but a 1.2-fold increase of MAPK expression; dbSNP:rs121908984 | |||
Sequence: H → N | ||||||
Natural variant | VAR_054385 | 148 | in PPGL1; dbSNP:rs1555187633 | |||
Sequence: G → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 407 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-56 | Mitochondrion | ||||
Sequence: MAVLWRLSAVCGALGGRALLLRTPVVRPAHISAFLQDRPIPEWCGVQHIHLSPSHH | ||||||
Chain | PRO_0000006487 | 57-159 | Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial | |||
Sequence: SGSKAASLHWTSERVVSVLLLGLLPAAYLNPCSAMDYSLAAALTLHGHWGLGQVVTDYVHGDALQKAAKAGLLALSALTFAGLCYFNYHDVGICKAVAMLWKL |
Proteomic databases
PTM databases
Expression
Interaction
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.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O14521 | RHBDD2 Q6NTF9-3 | 3 | EBI-1224553, EBI-17589229 |
Protein-protein interaction databases
Miscellaneous
Structure
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 4 isoforms produced by Alternative splicing.
O14521-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length159
- Mass (Da)17,043
- Last updated1998-01-01 v1
- Checksum6B1AA94831C8C3B6
O14521-2
- Name2
- Differences from canonical
- 19-57: Missing
O14521-3
- Name3
- Differences from canonical
- 56-158: HSGSKAASLHWTSERVVSVLLLGLLPAAYLNPCSAMDYSLAAALTLHGHWGLGQVVTDYVHGDALQKAAKAGLLALSALTFAGLCYFNYHDVGICKAVAMLWK → HWALDKLLLTMFMGMPCRKLPRQGFWHFQ
O14521-4
- Name4
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0AAQ5BHI1 | A0AAQ5BHI1_HUMAN | SDHD | 38 | ||
A0AAQ5BHF6 | A0AAQ5BHF6_HUMAN | SDHD | 143 | ||
A0AAQ5BHH5 | A0AAQ5BHH5_HUMAN | SDHD | 53 | ||
H0YD96 | H0YD96_HUMAN | SDHD | 111 | ||
G3V173 | G3V173_HUMAN | SDHD | 104 | ||
A0A1W2PNY0 | A0A1W2PNY0_HUMAN | SDHD | 72 | ||
E9PK73 | E9PK73_HUMAN | SDHD | 131 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_054744 | 19-57 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_054745 | 56-158 | in isoform 3 | |||
Sequence: HSGSKAASLHWTSERVVSVLLLGLLPAAYLNPCSAMDYSLAAALTLHGHWGLGQVVTDYVHGDALQKAAKAGLLALSALTFAGLCYFNYHDVGICKAVAMLWK → HWALDKLLLTMFMGMPCRKLPRQGFWHFQ | ||||||
Sequence conflict | 74 | in Ref. 8; AAH70307 | ||||
Sequence: V → F | ||||||
Alternative sequence | VSP_054746 | 106-143 | in isoform 4 | |||
Sequence: GLGQVVTDYVHGDALQKAAKAGLLALSALTFAGLCYFN → LECNGAILARHDLGSARSQLTATSAFRVQAILLPQPPK | ||||||
Alternative sequence | VSP_054747 | 144-159 | in isoform 4 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB006202 EMBL· GenBank· DDBJ | BAA22054.1 EMBL· GenBank· DDBJ | mRNA | ||
AB026906 EMBL· GenBank· DDBJ | BAA81889.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK075360 EMBL· GenBank· DDBJ | BAG52120.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007238 EMBL· GenBank· DDBJ | AAP35902.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456932 EMBL· GenBank· DDBJ | CAG33213.1 EMBL· GenBank· DDBJ | mRNA | ||
AP002007 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471065 EMBL· GenBank· DDBJ | EAW67181.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC005263 EMBL· GenBank· DDBJ | AAH05263.1 EMBL· GenBank· DDBJ | mRNA | ||
BC009574 EMBL· GenBank· DDBJ | AAH09574.1 EMBL· GenBank· DDBJ | mRNA | ||
BC012603 EMBL· GenBank· DDBJ | AAH12603.1 EMBL· GenBank· DDBJ | mRNA | ||
BC015188 EMBL· GenBank· DDBJ | AAH15188.1 EMBL· GenBank· DDBJ | mRNA | ||
BC015992 EMBL· GenBank· DDBJ | AAH15992.1 EMBL· GenBank· DDBJ | mRNA | ||
BC022350 EMBL· GenBank· DDBJ | AAH22350.1 EMBL· GenBank· DDBJ | mRNA | ||
BC070307 EMBL· GenBank· DDBJ | AAH70307.1 EMBL· GenBank· DDBJ | mRNA | ||
BC071755 EMBL· GenBank· DDBJ | AAH71755.1 EMBL· GenBank· DDBJ | mRNA | ||
BC071756 EMBL· GenBank· DDBJ | AAH71756.1 EMBL· GenBank· DDBJ | mRNA |