PDSS1 (decaprenyl-diphosphate synthase subunit 1; also DPS1/TPRT) is one of the two subunits of the human all-trans-decaprenyl-diphosphate synthase (trans-prenyltransferase, EC 2.5.1.91). Together with PDSS2, it forms a heterotetramer (2 PDSS1 + 2 PDSS2) that performs the first committed, chain-length-determining step of coenzyme Q10 (ubiquinone) biosynthesis: sequential head-to-tail condensation of (2E,6E)-farnesyl diphosphate (the primer) with multiple isopentenyl diphosphate (IPP) units, adding them with trans stereochemistry to build the all-trans C50 decaprenyl (and C45 nonaprenyl) polyisoprenoid diphosphate side chain. This polyprenyl tail is subsequently attached to the quinone ring (by COQ2) to yield ubiquinone-10 (and ubiquinone-9). The enzyme is a Mg(2+)-dependent member of the trans-isoprenyl diphosphate synthase (FPP/GGPP synthase) family and localizes to the mitochondrion, acting at the matrix/inner-membrane face where CoQ is assembled. Loss-of-function variants cause autosomal recessive primary coenzyme Q10 deficiency type 2 (COQ10D2), a multisystem mitochondrial disorder.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004659 prenyltransferase activity | IBA GO_REF:0000033 | MODIFY | Summary: Phylogenetic (IBA) inference of a generic prenyltransferase activity. This is correct but too general: the specific, experimentally supported molecular function of PDSS1 is all-trans-decaprenyl-diphosphate synthase activity (GO:0097269, EC 2.5.1.91), a child of prenyltransferase activity. Modify to the specific term. Reason: GO:0004659 is a true ancestor but PDSS1 has a defined, assayed trans-prenyltransferase activity; the specific term GO:0097269 should be used as the core molecular function. Proposed replacements: all-trans-decaprenyl-diphosphate synthase activity Supporting Evidence: file:human/PDSS1/PDSS1-uniprot.txt EC=2.5.1.91 |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) inference that PDSS1 is active in the mitochondrion. Consistent with the UniProt subcellular location call and with high-confidence human mitochondrial proteome data. Accept as the core localization. Supporting Evidence: file:human/PDSS1/PDSS1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0006744 ubiquinone biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) inference of involvement in ubiquinone biosynthesis. This is the core biological process for PDSS1: the decaprenyl-diphosphate synthase supplies the polyprenyl side chain of coenzyme Q. Directly supported experimentally (IDA, PMID:16262699). Accept as core. Supporting Evidence: file:human/PDSS1/PDSS1-uniprot.txt Cofactor biosynthesis; ubiquinone biosynthesis |
| GO:0008299 isoprenoid biosynthetic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) inference of involvement in isoprenoid biosynthesis. Correct but broad: this is a parent of the specific process (ubiquinone/polyprenyl-diphosphate biosynthesis). Keep as a valid but non-core, higher-level annotation. |
| GO:0032476 polyprenyl diphosphate synthase complex | IBA GO_REF:0000033 | MODIFY | Summary: Phylogenetic (IBA) inference that PDSS1 is part of a polyprenyl diphosphate synthase complex. Correct but general: the human enzyme is specifically a heterotetramer of PDSS1 and PDSS2, captured by the more specific child term GO:0032478. Modify to the specific complex term, which is directly supported (IDA, PMID:16262699). Reason: A more specific and experimentally supported complex term is available for the human PDSS1/PDSS2 heterotetramer. Proposed replacements: heterotetrameric polyprenyl diphosphate synthase complex Supporting Evidence: file:human/PDSS1/PDSS1-uniprot.txt Heterotetramer composed of 2 PDSS1/DPS1 and 2 PDSS2/DLP1 |
| GO:0004659 prenyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IEA) electronic annotation of generic prenyltransferase activity from the polyprenyl synthase domain (IPR000092). Correct but too general; the specific experimentally supported function is all-trans-decaprenyl-diphosphate synthase activity (GO:0097269). Modify to the specific term. Reason: Domain-based IEA gives only the family-level activity; the specific assayed activity GO:0097269 is preferred. Proposed replacements: all-trans-decaprenyl-diphosphate synthase activity |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation of mitochondrial location from the UniProt Subcellular Location mapping (SL-0173). Consistent with the experimental UniProt call (PMID:34800366), the IBA/HTP evidence, and the enzyme's role in mitochondrial CoQ assembly. Accept as core localization. Supporting Evidence: file:human/PDSS1/PDSS1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic annotation to the mitochondrial matrix, a more specific compartment than the experimentally established "Mitochondrion" call. It is biologically plausible (CoQ side-chain assembly occurs at the matrix/inner-membrane face and Reactome places this reaction in the matrix), but the precise sub-mitochondrial location is not directly demonstrated in the cached experimental sources. Keep as a plausible, non-core sub-localization. |
| GO:0008299 isoprenoid biosynthetic process | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic annotation of the broad isoprenoid biosynthetic process. Correct but a high-level parent of the specific ubiquinone/polyprenyl process. Keep as non-core. |
| GO:0097269 all-trans-decaprenyl-diphosphate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (RHEA:27802 / EC 2.5.1.91) of the specific all-trans-decaprenyl- diphosphate synthase activity. This is the core molecular function of PDSS1 and is directly supported experimentally (IDA, PMID:16262699). Accept. Supporting Evidence: file:human/PDSS1/PDSS1-uniprot.txt all-trans-decaprenyl diphosphate + 7 diphosphate |
| GO:0006744 ubiquinone biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (UniPathway UPA00232) of involvement in ubiquinone biosynthesis. Core biological process; concordant with the IBA and IDA (PMID:16262699) evidence. Accept. Supporting Evidence: file:human/PDSS1/PDSS1-uniprot.txt Cofactor biosynthesis; ubiquinone biosynthesis |
| GO:0032478 heterotetrameric polyprenyl diphosphate synthase complex | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation to the heterotetrameric polyprenyl diphosphate synthase complex. This is the correct, specific complex for the human PDSS1/PDSS2 enzyme and is directly supported experimentally (IDA, PMID:16262699). Accept as core. Supporting Evidence: file:human/PDSS1/PDSS1-uniprot.txt Heterotetramer composed of 2 PDSS1/DPS1 and 2 PDSS2/DLP1 |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: High-throughput (HTP) localization from a quantitative high-confidence human mitochondrial proteome. This is the primary experimental basis for the UniProt "Mitochondrion" subcellular location call. Accept as core localization. Supporting Evidence: file:human/PDSS1/PDSS1-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:34800366} |
| GO:0097269 all-trans-decaprenyl-diphosphate synthase activity | IDA PMID:16262699 Characterization of solanesyl and decaprenyl diphosphate syn... | ACCEPT | Summary: Direct experimental (IDA, contributes_to) annotation of decaprenyl-diphosphate synthase activity. Saiki et al. reconstituted the human hDPS1 (PDSS1) + hDLP1 (PDSS2) pair in E. coli and verified in vitro decaprenyl diphosphate synthase activity, producing Q10. The "contributes_to" qualifier is appropriate because activity requires the PDSS1/PDSS2 heterotetramer. This is the core molecular function. Accept. Supporting Evidence: PMID:16262699 double transformants expressing mSPS1 and mDLP1 or hDPS1 and hDLP1 produced Q9 or Q10, respectively, and an in vitro activity of solanesyl or decaprenyl diphosphate synthase was verified |
| GO:0032478 heterotetrameric polyprenyl diphosphate synthase complex | IDA PMID:16262699 Characterization of solanesyl and decaprenyl diphosphate syn... | ACCEPT | Summary: Direct experimental (IDA) annotation that PDSS1 is part of the heterotetrameric polyprenyl diphosphate synthase complex. Gel-filtration sizing established that the human/murine long-chain trans-prenyl diphosphate synthases are heterotetramers of hDPS1/hDLP1 (PDSS1/PDSS2). Accept as the core complex assignment. Supporting Evidence: PMID:16262699 as estimated by gel-filtration chromatography, indicates that they consist of heterotetramers |
| GO:0005515 protein binding | IPI PMID:16262699 Characterization of solanesyl and decaprenyl diphosphate syn... | MARK AS OVER ANNOTATED | Summary: IPI annotation recording the physical interaction of PDSS1 with PDSS2 (with/from UniProtKB:Q86YH6 = PDSS2). The interaction itself is real and central to function, but the bare "protein binding" term is uninformative. The biologically meaningful content (the PDSS1-PDSS2 heterotetramer) is far better captured by the complex CC term (GO:0032478) and the subunit role in core_functions. Mark as over-annotated rather than removed (experimental IPI). Reason: Bare protein binding (GO:0005515) adds no functional specificity; the specific PDSS1/PDSS2 partnership is represented by the heterotetrameric complex term. Supporting Evidence: PMID:16262699 heterotetramers composed of newly characterized hDPS1 (mSPS1) and hDLP1 (mDLP1) |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-2162253 | KEEP AS NON CORE | Summary: Traceable author statement (Reactome) placing the PDSS1/PDSS2 reaction in the mitochondrial matrix. Consistent with the ARBA matrix IEA and with CoQ side-chain assembly at the matrix/inner-membrane face. The precise compartment is not independently demonstrated in the cached primary experimental sources, so keep as a plausible non-core sub-localization. |
| GO:0006744 ubiquinone biosynthetic process | IDA PMID:16262699 Characterization of solanesyl and decaprenyl diphosphate syn... | ACCEPT | Summary: Direct experimental (IDA) annotation of involvement in ubiquinone biosynthesis. The reconstituted hDPS1/hDLP1 (PDSS1/PDSS2) enzyme determines the ubiquinone side chain and its expression yields Q10. This is the core biological process. Accept. Supporting Evidence: PMID:16262699 both components are involved in determining the ubiquinone side chain |
| GO:0008299 isoprenoid biosynthetic process | IDA PMID:16262699 Characterization of solanesyl and decaprenyl diphosphate syn... | KEEP AS NON CORE | Summary: Direct experimental (IDA) annotation of involvement in isoprenoid biosynthesis. True (the enzyme builds a polyisoprenoid diphosphate), but this is a broad parent of the specific ubiquinone/polyprenyl-diphosphate process. Keep as non-core. |
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