id: Q5T2R2
gene_symbol: PDSS1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: '1'
  id: Q5T2R2-1
- name: '2'
  id: Q5T2R2-2
  sequence_note: VSP_017101
- name: '3'
  id: Q5T2R2-3
  sequence_note: VSP_017100
existing_annotations:
- term:
    id: GO:0004659
    label: prenyltransferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0097269
      label: all-trans-decaprenyl-diphosphate synthase activity
    supported_by:
    - reference_id: file:human/PDSS1/PDSS1-uniprot.txt
      supporting_text: "EC=2.5.1.91"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/PDSS1/PDSS1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Mitochondrion"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0006744
    label: ubiquinone biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/PDSS1/PDSS1-uniprot.txt
      supporting_text: "Cofactor biosynthesis; ubiquinone biosynthesis"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0008299
    label: isoprenoid biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0032476
    label: polyprenyl diphosphate synthase complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    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).
    action: MODIFY
    reason: >-
      A more specific and experimentally supported complex term is available for the human
      PDSS1/PDSS2 heterotetramer.
    proposed_replacement_terms:
    - id: GO:0032478
      label: heterotetrameric polyprenyl diphosphate synthase complex
    supported_by:
    - reference_id: file:human/PDSS1/PDSS1-uniprot.txt
      supporting_text: "Heterotetramer composed of 2 PDSS1/DPS1 and 2 PDSS2/DLP1"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0004659
    label: prenyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: MODIFY
    reason: >-
      Domain-based IEA gives only the family-level activity; the specific assayed activity
      GO:0097269 is preferred.
    proposed_replacement_terms:
    - id: GO:0097269
      label: all-trans-decaprenyl-diphosphate synthase activity
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/PDSS1/PDSS1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Mitochondrion"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0008299
    label: isoprenoid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0097269
    label: all-trans-decaprenyl-diphosphate synthase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/PDSS1/PDSS1-uniprot.txt
      supporting_text: "all-trans-decaprenyl diphosphate + 7 diphosphate"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0006744
    label: ubiquinone biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Electronic annotation (UniPathway UPA00232) of involvement in ubiquinone biosynthesis.
      Core biological process; concordant with the IBA and IDA (PMID:16262699) evidence.
      Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/PDSS1/PDSS1-uniprot.txt
      supporting_text: "Cofactor biosynthesis; ubiquinone biosynthesis"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0032478
    label: heterotetrameric polyprenyl diphosphate synthase complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/PDSS1/PDSS1-uniprot.txt
      supporting_text: "Heterotetramer composed of 2 PDSS1/DPS1 and 2 PDSS2/DLP1"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/PDSS1/PDSS1-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:34800366}"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0097269
    label: all-trans-decaprenyl-diphosphate synthase activity
  evidence_type: IDA
  original_reference_id: PMID:16262699
  qualifier: contributes_to
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:16262699
      supporting_text: >-
        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
      reference_section_type: ABSTRACT
- term:
    id: GO:0032478
    label: heterotetrameric polyprenyl diphosphate synthase complex
  evidence_type: IDA
  original_reference_id: PMID:16262699
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:16262699
      supporting_text: >-
        as estimated by
        gel-filtration chromatography, indicates that they consist of heterotetramers
      reference_section_type: ABSTRACT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16262699
  qualifier: enables
  review:
    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).
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Bare protein binding (GO:0005515) adds no functional specificity; the specific
      PDSS1/PDSS2 partnership is represented by the heterotetrameric complex term.
    supported_by:
    - reference_id: PMID:16262699
      supporting_text: >-
        heterotetramers composed of newly characterized hDPS1
        (mSPS1) and hDLP1 (mDLP1)
      reference_section_type: ABSTRACT
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2162253
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0006744
    label: ubiquinone biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:16262699
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:16262699
      supporting_text: >-
        both components are
        involved in determining the ubiquinone side chain
      reference_section_type: ABSTRACT
- term:
    id: GO:0008299
    label: isoprenoid biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:16262699
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
core_functions:
- description: >-
    All-trans-decaprenyl-diphosphate synthase (trans-prenyltransferase, EC 2.5.1.91): as a
    subunit of the PDSS1/PDSS2 heterotetramer, catalyzes the Mg(2+)-dependent sequential
    head-to-tail (trans) condensation of (2E,6E)-farnesyl diphosphate with seven isopentenyl
    diphosphate units to form all-trans-decaprenyl diphosphate (and, with six IPP units, the
    nonaprenyl diphosphate), the chain-length-determining step that builds the polyprenyl side
    chain of coenzyme Q10/Q9.
  molecular_function:
    id: GO:0097269
    label: all-trans-decaprenyl-diphosphate synthase activity
  supported_by:
  - reference_id: PMID:16262699
    supporting_text: >-
      an in vitro activity of solanesyl or
      decaprenyl diphosphate synthase was verified
  - reference_id: file:human/PDSS1/PDSS1-uniprot.txt
    supporting_text: "all-trans-decaprenyl diphosphate + 7 diphosphate"
  directly_involved_in:
  - id: GO:0006744
    label: ubiquinone biosynthetic process
  in_complex:
    id: GO:0032478
    label: heterotetrameric polyprenyl diphosphate synthase complex
  locations:
  - id: GO:0005739
    label: mitochondrion
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:16262699
  title: Characterization of solanesyl and decaprenyl diphosphate synthases in mice
    and humans.
  findings:
  - statement: >-
      Human hDPS1 (PDSS1) and hDLP1 (PDSS2) form a heterotetrameric decaprenyl diphosphate
      synthase; reconstitution in E. coli verifies in vitro decaprenyl diphosphate synthase
      activity and Q10 production, and both subunits contribute to determining the ubiquinone
      side chain.
    reference_section_type: ABSTRACT
    supporting_text: >-
      murine and human solanesyl and decaprenyl
      diphosphate synthases are heterotetramers composed of newly characterized hDPS1
      (mSPS1) and hDLP1 (mDLP1)
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Abstract-only in local cache (full_text_available: false). PubMed-verified as the primary
      characterization of human PDSS1/PDSS2; directly supports the decaprenyl-diphosphate
      synthase activity, heterotetramer, and ubiquinone-biosynthesis annotations.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings:
  - statement: >-
      High-confidence quantitative human mitochondrial proteome; the experimental basis for the
      UniProt mitochondrial subcellular-location call for PDSS1.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Full text cached. Large-scale mitochondrial proteome; PDSS1 is part of the proteome
      dataset rather than named in prose, consistent with the HTP localization annotation.
- id: Reactome:R-HSA-2162253
  title: PDSS1,2 ligates FPP to IPPP
  findings:
  - statement: >-
      Reactome reaction: the PDSS1/PDSS2 tetramer condenses (2E,6E)-farnesyl diphosphate with
      seven isopentenyl diphosphate to form all-trans-decaprenyl diphosphate in the
      mitochondrial matrix.
    reference_section_type: OTHER
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reactome curation consistent with UniProt and Saiki et al. 2005; supports the matrix
      localization and the reaction catalyzed by the heterotetramer.