Q96H96 · COQ2_HUMAN
- Protein4-hydroxybenzoate polyprenyltransferase, mitochondrial
- GeneCOQ2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids371 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Mediates the second step in the final reaction sequence of coenzyme Q (CoQ) biosynthesis (PubMed:15153069, PubMed:16400613, PubMed:17374725, PubMed:20526342).
Catalyzes the prenylation of para-hydroxybenzoate (PHB) with an all-trans polyprenyl donor (such as all-trans-decaprenyl diphosphate) (PubMed:15153069, PubMed:16400613, PubMed:17374725, PubMed:20526342).
The length of the polyprenyl side chain varies depending on the species, in humans, the side chain is comprised of 10 isoprenyls (decaprenyl) producing CoQ10 (also known as ubiquinone), whereas rodents predominantly generate CoQ9 (PubMed:15153069, PubMed:16400613).
However, this specificity is not complete, human tissues have low amounts of CoQ9 and rodent organs contain some CoQ10 (PubMed:15153069).
Plays a central role in the biosynthesis of CoQ10 (PubMed:15153069, PubMed:16400613, PubMed:17374725).
CoQ10 is a vital molecule that transports electrons from mitochondrial respiratory chain complexes (PubMed:16400613, PubMed:17374725, PubMed:27493029).
CoQs also function as cofactors for uncoupling protein and play a role as regulators of the extracellularly-induced ceramide-dependent apoptotic pathway (PubMed:16400613, PubMed:17374725).
Regulates mitochondrial permeability transition pore (mPTP) opening and ROS production (pivotal events in cell death) in a tissue specific manner (By similarity).
Catalyzes the prenylation of para-hydroxybenzoate (PHB) with an all-trans polyprenyl donor (such as all-trans-decaprenyl diphosphate) (PubMed:15153069, PubMed:16400613, PubMed:17374725, PubMed:20526342).
The length of the polyprenyl side chain varies depending on the species, in humans, the side chain is comprised of 10 isoprenyls (decaprenyl) producing CoQ10 (also known as ubiquinone), whereas rodents predominantly generate CoQ9 (PubMed:15153069, PubMed:16400613).
However, this specificity is not complete, human tissues have low amounts of CoQ9 and rodent organs contain some CoQ10 (PubMed:15153069).
Plays a central role in the biosynthesis of CoQ10 (PubMed:15153069, PubMed:16400613, PubMed:17374725).
CoQ10 is a vital molecule that transports electrons from mitochondrial respiratory chain complexes (PubMed:16400613, PubMed:17374725, PubMed:27493029).
CoQs also function as cofactors for uncoupling protein and play a role as regulators of the extracellularly-induced ceramide-dependent apoptotic pathway (PubMed:16400613, PubMed:17374725).
Regulates mitochondrial permeability transition pore (mPTP) opening and ROS production (pivotal events in cell death) in a tissue specific manner (By similarity).
Catalytic activity
- 4-hydroxybenzoate + an all-trans-polyprenyl diphosphate = a 4-hydroxy-3-all-trans-polyprenylbenzoate + diphosphateThis reaction proceeds in the forward direction.
CHEBI:17879 + an all-trans-polyprenyl diphosphate RHEA-COMP:9564 = a 4-hydroxy-3-all-trans-polyprenylbenzoate RHEA-COMP:9514 + CHEBI:33019
Cofactor
Pathway
Cofactor biosynthesis; ubiquinone biosynthesis.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial inner membrane | |
Molecular Function | 4-hydroxybenzoate decaprenyltransferase activity | |
Molecular Function | 4-hydroxybenzoate nonaprenyltransferase activity | |
Molecular Function | 4-hydroxybenzoate octaprenyltransferase activity | |
Molecular Function | prenyltransferase activity | |
Biological Process | glycerol metabolic process | |
Biological Process | isoprenoid biosynthetic process | |
Biological Process | ubiquinone biosynthetic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name4-hydroxybenzoate polyprenyltransferase, mitochondrial
- EC number
- Short names4-HB polyprenyltransferase
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ96H96
- 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 | 35-83 | Mitochondrial matrix | ||||
Sequence: AGAPHGGDLQPPACPEPRGRQLSLSAAAVVDSAPRPLQPYLRLMRLDKP | ||||||
Transmembrane | 84-104 | Helical | ||||
Sequence: IGTWLLYLPCTWSIGLAAEPG | ||||||
Topological domain | 105-108 | Mitochondrial intermembrane | ||||
Sequence: CFPD | ||||||
Transmembrane | 109-129 | Helical | ||||
Sequence: WYMLSLFGTGAILMRGAGCTI | ||||||
Topological domain | 130-148 | Mitochondrial matrix | ||||
Sequence: NDMWDQDYDKKVTRTANRP | ||||||
Transmembrane | 149-169 | Helical | ||||
Sequence: IAAGDISTFQSFVFLGGQLTL | ||||||
Topological domain | 170-172 | Mitochondrial intermembrane | ||||
Sequence: ALG | ||||||
Transmembrane | 173-193 | Helical | ||||
Sequence: VLLCLNYYSIALGAGSLLLVI | ||||||
Topological domain | 194-203 | Mitochondrial matrix | ||||
Sequence: TYPLMKRISY | ||||||
Transmembrane | 204-224 | Helical | ||||
Sequence: WPQLALGLTFNWGALLGWSAI | ||||||
Topological domain | 225-231 | Mitochondrial intermembrane | ||||
Sequence: KGSCDPS | ||||||
Transmembrane | 232-252 | Helical | ||||
Sequence: VCLPLYFSGVMWTLIYDTIYA | ||||||
Topological domain | 253-277 | Mitochondrial matrix | ||||
Sequence: HQDKRDDVLIGLKSTALRFGENTKP | ||||||
Transmembrane | 278-298 | Helical | ||||
Sequence: WLSGFSVAMLGALSLVGVNSG | ||||||
Topological domain | 299-300 | Mitochondrial intermembrane | ||||
Sequence: QT | ||||||
Transmembrane | 301-321 | Helical | ||||
Sequence: APYYAALGAVGAHLTHQIYTL | ||||||
Topological domain | 322-332 | Mitochondrial matrix | ||||
Sequence: DIHRPEDCWNK | ||||||
Transmembrane | 333-353 | Helical | ||||
Sequence: FISNRTLGLIVFLGIVLGNLW | ||||||
Topological domain | 354-371 | Mitochondrial intermembrane | ||||
Sequence: KEKKTDKTKKGIENKIEN |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Coenzyme Q10 deficiency, primary, 1 (COQ10D1)
- Note
- DescriptionAn autosomal recessive disorder with variable manifestations consistent with 5 major phenotypes. The phenotypes include an encephalomyopathic form with seizures and ataxia; a multisystem infantile form with encephalopathy, cardiomyopathy and renal failure; a predominantly cerebellar form with ataxia and cerebellar atrophy; Leigh syndrome with growth retardation; and an isolated myopathic form.
- See alsoMIM:607426
Natural variants in COQ10D1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_089039 | 53 | G>S | in COQ10D1; uncertain significance | |
VAR_068161 | 96 | S>N | in COQ10D1; decreased ubiquinone biosynthesis; dbSNP:rs121918233 | |
VAR_076913 | 132 | M>R | in COQ10D1; decreased ubiquinone biosynthesis; dbSNP:rs1057519348 | |
VAR_068162 | 147 | R>H | in COQ10D1; loss of ubiquinone biosynthesis; dbSNP:rs121918231 | |
VAR_068163 | 178 | N>S | in COQ10D1; decreased ubiquinone biosynthesis; dbSNP:rs121918232 | |
VAR_025701 | 247 | Y>C | in COQ10D1; decreased 4-hydroxybenzoate decaprenyltransferase activity; dbSNP:rs121918230 | |
VAR_076914 | 252 | A>V | in COQ10D1; loss of ubiquinone biosynthesis; dbSNP:rs762616589 | |
VAR_078121 | 340 | G>A | in COQ10D1; uncertain significance; dbSNP:rs752608037 |
Multiple system atrophy 1 (MSA1)
- Note
- DescriptionA progressive neurodegenerative disorder clinically characterized by parkinsonism, cerebellar ataxia, and autonomic, urogenital, and pyramidal dysfunction in various combinations. Pathologically, it is characterized by degeneration of striatonigral and olivopontocerebellar structures, and glial cytoplasmic inclusions that consist of abnormally phosphorylated alpha-synuclein or tau.
- See alsoMIM:146500
Natural variants in MSA1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_070239 | 29 | F>L | in MSA1; associated with disease susceptibility; dbSNP:rs863223933 | |
VAR_070240 | 49 | P>H | in MSA1; associated with disease susceptibility; dbSNP:rs936872920 | |
VAR_070241 | 57 | S>T | in MSA1; associated with disease susceptibility; dbSNP:rs550949678 | |
VAR_070243 | 78 | M>V | in MSA1; associated with disease susceptibility; decreased ubiquinone biosynthesis; dbSNP:rs778094136 | |
VAR_070244 | 97 | I>T | in MSA1; associated with disease susceptibility; dbSNP:rs944546272 | |
VAR_070245 | 107 | P>S | in MSA1; associated with disease susceptibility; dbSNP:rs1462568548 | |
VAR_070246 | 113 | S>F | in MSA1; associated with disease susceptibility; dbSNP:rs1735249512 | |
VAR_070247 | 267 | T>A | in MSA1; associated with disease susceptibility; dbSNP:rs369627290 | |
VAR_070248 | 297 | S>C | in MSA1; associated with disease susceptibility; dbSNP:rs566845170 | |
VAR_070250 | 337 | R>Q | in MSA1; associated with disease susceptibility; dbSNP:rs763562410 | |
VAR_070251 | 343 | V>A | in MSA1; associated with disease susceptibility; dbSNP:rs148156462 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_070237 | 16 | in dbSNP:rs6818847 | |||
Sequence: V → L | ||||||
Natural variant | VAR_070238 | 22 | in dbSNP:rs765747895 | |||
Sequence: P → L | ||||||
Natural variant | VAR_070239 | 29 | in MSA1; associated with disease susceptibility; dbSNP:rs863223933 | |||
Sequence: F → L | ||||||
Natural variant | VAR_070240 | 49 | in MSA1; associated with disease susceptibility; dbSNP:rs936872920 | |||
Sequence: P → H | ||||||
Natural variant | VAR_089039 | 53 | in COQ10D1; uncertain significance | |||
Sequence: G → S | ||||||
Natural variant | VAR_070241 | 57 | in MSA1; associated with disease susceptibility; dbSNP:rs550949678 | |||
Sequence: S → T | ||||||
Natural variant | VAR_070242 | 69 | in dbSNP:rs762399579 | |||
Sequence: R → H | ||||||
Natural variant | VAR_070243 | 78 | in MSA1; associated with disease susceptibility; decreased ubiquinone biosynthesis; dbSNP:rs778094136 | |||
Sequence: M → V | ||||||
Natural variant | VAR_068161 | 96 | in COQ10D1; decreased ubiquinone biosynthesis; dbSNP:rs121918233 | |||
Sequence: S → N | ||||||
Natural variant | VAR_070244 | 97 | in MSA1; associated with disease susceptibility; dbSNP:rs944546272 | |||
Sequence: I → T | ||||||
Natural variant | VAR_070245 | 107 | in MSA1; associated with disease susceptibility; dbSNP:rs1462568548 | |||
Sequence: P → S | ||||||
Natural variant | VAR_070246 | 113 | in MSA1; associated with disease susceptibility; dbSNP:rs1735249512 | |||
Sequence: S → F | ||||||
Natural variant | VAR_076913 | 132 | in COQ10D1; decreased ubiquinone biosynthesis; dbSNP:rs1057519348 | |||
Sequence: M → R | ||||||
Natural variant | VAR_068162 | 147 | in COQ10D1; loss of ubiquinone biosynthesis; dbSNP:rs121918231 | |||
Sequence: R → H | ||||||
Natural variant | VAR_068163 | 178 | in COQ10D1; decreased ubiquinone biosynthesis; dbSNP:rs121918232 | |||
Sequence: N → S | ||||||
Natural variant | VAR_025701 | 247 | in COQ10D1; decreased 4-hydroxybenzoate decaprenyltransferase activity; dbSNP:rs121918230 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_076914 | 252 | in COQ10D1; loss of ubiquinone biosynthesis; dbSNP:rs762616589 | |||
Sequence: A → V | ||||||
Natural variant | VAR_070247 | 267 | in MSA1; associated with disease susceptibility; dbSNP:rs369627290 | |||
Sequence: T → A | ||||||
Natural variant | VAR_070248 | 297 | in MSA1; associated with disease susceptibility; dbSNP:rs566845170 | |||
Sequence: S → C | ||||||
Natural variant | VAR_070249 | 336 | in dbSNP:rs1734859571 | |||
Sequence: N → H | ||||||
Natural variant | VAR_070250 | 337 | in MSA1; associated with disease susceptibility; dbSNP:rs763562410 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_078121 | 340 | in COQ10D1; uncertain significance; dbSNP:rs752608037 | |||
Sequence: G → A | ||||||
Natural variant | VAR_070251 | 343 | in MSA1; associated with disease susceptibility; dbSNP:rs148156462 | |||
Sequence: V → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 490 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-34 | Mitochondrion | ||||
Sequence: MLGSRAAGFARGLRAVALAWLPGWRGRSFALARA | ||||||
Chain | PRO_0000228623 | 35-371 | 4-hydroxybenzoate polyprenyltransferase, mitochondrial | |||
Sequence: AGAPHGGDLQPPACPEPRGRQLSLSAAAVVDSAPRPLQPYLRLMRLDKPIGTWLLYLPCTWSIGLAAEPGCFPDWYMLSLFGTGAILMRGAGCTINDMWDQDYDKKVTRTANRPIAAGDISTFQSFVFLGGQLTLALGVLLCLNYYSIALGAGSLLLVITYPLMKRISYWPQLALGLTFNWGALLGWSAIKGSCDPSVCLPLYFSGVMWTLIYDTIYAHQDKRDDVLIGLKSTALRFGENTKPWLSGFSVAMLGALSLVGVNSGQTAPYYAALGAVGAHLTHQIYTLDIHRPEDCWNKFISNRTLGLIVFLGIVLGNLWKEKKTDKTKKGIENKIEN |
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed. Present in all of the tissues tested. Expressed at higher level in skeletal muscle, adrenal glands and the heart.
Gene expression databases
Organism-specific databases
Structure
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 5 isoforms produced by Alternative splicing & Alternative initiation.
Q96H96-1
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
- Length371
- Mass (Da)40,475
- Last updated2022-10-12 v2
- Checksum8BCE473A1D0C60CB
Q96H96-3
- Name3
Q96H96-4
- Name4
- NotePotential minor and functional isoform produced by alternative initiation.
- Differences from canonical
- 1-1: M → MTPISQVRMRKGSAHTAAQPGRLGLHPAGATAHACRGMTSIRARPGLTSAM
Q96H96-5
- Name5
- NotePotential minor and functional isoform produced by alternative initiation.
- Differences from canonical
- 1-1: M → MRKGSAHTAAQPGRLGLHPAGATAHACRGMTSIRARPGLTSAM
Q96H96-6
- Name6
- NotePotential minor and functional isoform produced by alternative initiation.
- Differences from canonical
- 1-1: M → MTSIRARPGLTSAM
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_061606 | 1 | in isoform 4 | |||
Sequence: M → MTPISQVRMRKGSAHTAAQPGRLGLHPAGATAHACRGMTSIRARPGLTSAM | ||||||
Alternative sequence | VSP_061607 | 1 | in isoform 5 | |||
Sequence: M → MRKGSAHTAAQPGRLGLHPAGATAHACRGMTSIRARPGLTSAM | ||||||
Alternative sequence | VSP_061608 | 1 | in isoform 6 | |||
Sequence: M → MTSIRARPGLTSAM | ||||||
Alternative sequence | VSP_017677 | 318-334 | in isoform 3 | |||
Sequence: IYTLDIHRPEDCWNKFI → KWGLEILPRLV | ||||||
Alternative sequence | VSP_017678 | 335-371 | in isoform 3 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ621061 EMBL· GenBank· DDBJ | CAF18241.1 EMBL· GenBank· DDBJ | mRNA | ||
KU877220 EMBL· GenBank· DDBJ | AOT85942.1 EMBL· GenBank· DDBJ | mRNA | ||
AC114781 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC008804 EMBL· GenBank· DDBJ | AAH08804.1 EMBL· GenBank· DDBJ | mRNA | ||
BC020728 EMBL· GenBank· DDBJ | AAH20728.2 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC116454 EMBL· GenBank· DDBJ | AAI16455.1 EMBL· GenBank· DDBJ | mRNA | ||
AF091086 EMBL· GenBank· DDBJ | AAC72955.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
CR456860 EMBL· GenBank· DDBJ | CAG33141.1 EMBL· GenBank· DDBJ | mRNA |