DHDDS

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016094 polyprenol biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: DHDDS executes the chain-elongation step supplying long-chain polyprenols. Reason: The PTHR10291 polyprenol-biosynthesis IBD is at PTN000033324, an actual ancestor of human Q86SQ9. Its bacterial descendant evidence concerns the conserved precursor-producing chemistry; it does not assign bacterial cell-wall synthesis to DHDDS. Human DHDDS–NUS1 makes long-chain polyprenyl diphosphates, which are converted to polyprenols and dolichol. This is participation through catalysis, not a downstream phenotype. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000033324 SUPPORTS TRANSFER The literal polyprenol IBD and 21-node target lineage support inherited precursor synthesis; target experiments corroborate the chemistry.
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	MODIFY	Summary: Refine the valid ER localization to the ER membrane. Reason: The ER IBD at PTN000033327 is on the target lineage and includes legitimate human experimental grounding. PMID:14652022 reports human cDNA expression in CHO cells, microsomal cis-prenyltransferase activity and calnexin colocalization; PMID:21572394 independently places hCIT in membrane fractions. GO:0005789 therefore states the supported specific compartment. This term already occurs in the imported annotations; refinement adds no new biological coverage. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000033327 SUPPORTS TRANSFER Valid ancestral ER placement, refined using target-specific membrane evidence rather than rejected as erroneous. Proposed replacements: endoplasmic reticulum membrane
GO:0045547 ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity	IBA GO_REF:0000033	ACCEPT	Summary: The inherited, complex-dependent cis-prenyltransferase activity is supported. Reason: PTN000033324 is ancestral to human DHDDS, and its GO:0045547 IBD includes fungal and human experimental descendants. Target self-inclusion is legitimate grounding. Human biochemical and structural studies show that DHDDS supplies the catalytic pocket while the NUS1 C-terminal tail contributes across the interface. The imported contributes_to assertion accurately accommodates this cooperative activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000033324 SUPPORTS TRANSFER The specific MF IBD lies on the target lineage and is corroborated by direct human complex assays; no target loss is indicated.
GO:1904423 dehydrodolichyl diphosphate synthase complex	IBA GO_REF:0000033	ACCEPT	Summary: DHDDS is a constituent of the cis-prenyltransferase complex. Reason: The complex-membership IBD at PTN000815958 lies on the metazoan/choanoflagellate portion of the human lineage. Its human self-source is valid experimental grounding, not circularity. Purification and structures establish DHDDS–NUS1 heterodimeric units; solution measurements further support a 2:2 assembly. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000815958 SUPPORTS TRANSFER Actual ancestral placement agrees with experimentally established human DHDDS–NUS1 complex membership.
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: The UniProt subcellular-location mapping correctly identifies the ER membrane. Reason: The source is UniProtKB-SubCell:SL-0097, matching the curated DHDDS ER-membrane location. Human cDNA localization and microsomal activity in PMID:14652022 independently support it. DHDDS is peripherally associated; this is not an assertion that DHDDS itself spans the membrane. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0097 SUPPORTS TRANSFER The source ER-membrane term matches the target record and independent localization evidence.
GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups	IEA GO_REF:0000002	MODIFY	Summary: Replace the broad transferase mapping with the demonstrated specific cis-prenyltransferase activity. Reason: The actual InterPro2GO mappings for IPR001441, IPR018520 and IPR036424 all supply GO:0016765. This is a sound broad family/fold mapping, not an excessive claim. Human assays establish extension of FPP with IPP, supporting GO:0045547. That specific activity is already represented by other source rows; this refinement does not manufacture an additional assay or function. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: InterPro:IPR001441 SUPPORTS TRANSFER Current literal InterPro2GO mapping supports the broad alkyl-transferase branch; human substrate evidence permits GO:0045547 refinement. InterPro:IPR018520 SUPPORTS TRANSFER Current literal InterPro2GO mapping supports the broad alkyl-transferase branch; human substrate evidence permits GO:0045547 refinement. InterPro:IPR036424 SUPPORTS TRANSFER Current literal InterPro2GO mapping supports the broad alkyl-transferase branch; human substrate evidence permits GO:0045547 refinement. Proposed replacements: ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity
GO:0045547 ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity	IEA GO_REF:0000120	ACCEPT	Summary: The EC/Rhea-derived specific activity agrees with human biochemical evidence. Reason: The imported RHEA:53008/EC:2.5.1.87 sources describe repeated IPP condensation onto FPP to form di-trans,poly-cis-polyprenyl diphosphate. This is the measured reaction of the human complex. Retaining the catalytic-subunit annotation does not mean that isolated DHDDS reproduces the physiological complex rate or that NUS1 makes no active-site contribution. Propagation Review Root cause: NO FAILURE CORE Sources checked: RHEA:53008 SUPPORTS TRANSFER The curated reaction corresponds to the directly assayed FPP/IPP condensation performed by the DHDDS–NUS1 complex. EC:2.5.1.87 SUPPORTS TRANSFER The curated reaction corresponds to the directly assayed FPP/IPP condensation performed by the DHDDS–NUS1 complex.
GO:0005515 protein binding	IPI PMID:32817466 Structural elucidation of the cis-prenyltransferase NgBR/DHD...	MODIFY	Summary: Specify formation of the experimentally demonstrated DHDDS–NUS1 heterodimeric unit. Reason: The GOA partner is NUS1/Q96E22. PMID:32817466 resolves human DHDDS 1–333 with NgBR 79–293 and tests their contact interface. Binding between these nonidentical subunits meets GO:0046982. The heterodimer is a unit of the 2:2 assembly established in PMID:33077723, not a claim that the entire native complex is exclusively 1:1. No autonomous NUS1 enzyme activity or DHDDS adaptor activity is inferred. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:32817466 the crystal structure of the human NgBR/DHDDS complex
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MODIFY	Summary: Refine the NUS1 association using independently established heterodimer formation. Reason: The literal BioPlex source pair is Q86SQ9–Q96E22: IM-29278-16507 and IM-29278-28587 in HEK293T, and IM-29278-26011 in HCT116. The records are positive anti-tag co-immunoprecipitation/AP-MS, with sequence/taxon identifiers matching canonical human proteins and a C-terminal tandem tag on the bait. These assays establish co-complex association, not binary contact or stoichiometry by themselves. Independent human structural/interface evidence in PMID:32817466 establishes the same pair as a heterodimeric unit, permitting GO:0046982; the full complex can be 2:2. Proposed replacements: protein heterodimerization activity
GO:0005789 endoplasmic reticulum membrane	NAS PMID:32817466 Structural elucidation of the cis-prenyltransferase NgBR/DHD...	ACCEPT	Summary: The stated ER-membrane location agrees with direct target evidence. Reason: The source paper discusses the human cis-prenyltransferase as an ER-associated complex. The NAS assertion is consistent with human-cDNA calnexin colocalization and microsomal activity in PMID:14652022 and membrane partitioning in PMID:21572394. Neither a soluble crystallization construct nor NUS1 truncation changes the supported cellular location.
GO:0006489 dolichyl diphosphate biosynthetic process	IDA PMID:32817466 Structural elucidation of the cis-prenyltransferase NgBR/DHD...	ACCEPT	Summary: DHDDS contributes an enzymatic precursor-synthesis step to dolichyl diphosphate biosynthesis. Reason: PMID:32817466 directly measures FPP/IPP-dependent long-chain product synthesis by the human complex, including product analysis after dephosphorylation. DHDDS performs precursor-chain synthesis within the biosynthetic pathway; the unsaturated dehydrodolichyl/polyprenyl diphosphate immediate product does not exclude this upstream catalytic participation. The established GO:0006489 assertion is included in the core alongside GO:0043048. Neither term is an ancestor of the other in the checked ontology. This pathway coverage does not identify the unsaturated immediate product as a saturated dolichol derivative or assign downstream reduction and phosphorylation to DHDDS.
GO:1904423 dehydrodolichyl diphosphate synthase complex	IPI PMID:32817466 Structural elucidation of the cis-prenyltransferase NgBR/DHD...	ACCEPT	Summary: The human complex structure directly establishes DHDDS membership. Reason: PMID:32817466 determines the DHDDS–NgBR heterodimer and experimentally tests subunit contacts. The later solution 2:2 architecture refines assembly stoichiometry without contradicting this complex-membership assertion.
GO:0043048 dolichyl monophosphate biosynthetic process	IDA PMID:28842490 A conserved C-terminal RXG motif in the NgBR subunit of cis-...	ACCEPT	Summary: DHDDS catalyses a precursor-producing step in dolichyl monophosphate biosynthesis. Reason: PMID:28842490 purifies the human DHDDS–NgBR complex from Expi293F membranes and measures FPP/IPP-dependent cis-prenyltransferase activity. Producing the long-chain precursor is work performed in the biosynthetic pathway, not merely evidence that DHDDS is necessary for downstream glycosylation. The immediate product is unsaturated diphosphate; this process annotation does not assign the later reductase or kinase reactions to DHDDS.
GO:0043048 dolichyl monophosphate biosynthetic process	IDA PMID:33077723 Structural basis of heterotetrameric assembly and disease mu...	ACCEPT	Summary: The measured cis-prenyltransferase step supplies dolichyl monophosphate biosynthesis. Reason: PMID:33077723 Figure 1a depicts precursor formation, Figure 1d measures human-complex activity, and the Enzyme kinetics Methods specify Mg2+-dependent FPP/[14C]IPP incorporation. DHDDS performs precursor-chain synthesis for dolichyl monophosphate biosynthesis. The imported process and existing GO-CAM activity agree; neither implies that DHDDS alone converts its immediate unsaturated diphosphate product into dolichyl monophosphate. Supporting Evidence: PMID:33077723
GO:0004659 prenyltransferase activity	IDA PMID:25066056 Mutation of Nogo-B receptor, a subunit of cis-prenyltransfer...	MODIFY	Summary: Specify the FPP-dependent long-chain cis-prenyltransferase reaction. Reason: PMID:25066056 tests human hCIT/DHDDS with NgBR in a yeast strain lacking the endogenous cis-prenyltransferase subunits, and in co-translation assays. The paired human subunits produce long-chain prenols; separately translated proteins mixed afterwards did not reproduce activity. GO:0045547 specifies the demonstrated chemistry more accurately than generic prenyltransferase activity, while the source contributes_to qualification remains intact. Proposed replacements: ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity Supporting Evidence: PMID:25066056
GO:0045547 ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity	EXP PMID:25066056 Mutation of Nogo-B receptor, a subunit of cis-prenyltransfer...	ACCEPT	Summary: Human DHDDS contributes the catalytic pocket of the assayed long-chain cis-prenyltransferase. Reason: PMID:25066056 explicitly assays the human hCIT–NgBR pair, although the title foregrounds NUS1. Complementation, microsomal assays and co-translation-dependent long-chain product synthesis support the specific reaction. This evidence concerns the cooperative complex and does not establish equivalent activity for all natural DHDDS products. Supporting Evidence: PMID:25066056 only co-translation of Nus1 with Rer2 and its orthologs in S.pombe or humans, formed an active cis-PTase complex
GO:0045547 ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity	EXP PMID:32817466 Structural elucidation of the cis-prenyltransferase NgBR/DHD...	ACCEPT	Summary: Structural and biochemical results support the specific human cis-prenyltransferase activity. Reason: PMID:32817466 assays human DHDDS 1–333/NgBR complexes with FPP and radiolabeled IPP and characterizes long-chain products. Its crystal contains IPP in both binding sites; the FPP-bound structure is from PMID:33077723. The chemistry is supported by the activity assays, not by incorrectly calling the bound ligand FPP. NUS1 participates at the catalytic interface.
GO:0005789 endoplasmic reticulum membrane	IDA PMID:14652022 Identification and characterization of a cDNA encoding a lon...	ACCEPT	Summary: Human DHDDS is active at the ER membrane. Reason: The PMID:14652022 abstract explicitly reports a human brain cDNA, expression in CHO cells, increased microsomal cis-prenyltransferase activity, and colocalization with calnexin. The full article was not recovered, so finer imaging or fractionation details are not asserted. This direct target-specific report and independent membrane-partitioning evidence support the curator’s localization decision. Supporting Evidence: PMID:14652022 co-localizes with calnexin in the ER, the site of Dol-P biosynthesis
GO:0045547 ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity	IDA PMID:33077723 Structural basis of heterotetrameric assembly and disease mu...	ACCEPT	Summary: The human complex directly catalyses the FPP/IPP condensation reaction. Reason: PMID:33077723 uses full-length 333-residue human DHDDS and an engineered soluble NgBR construct, measures Mg2+-dependent radiolabeled IPP incorporation, and resolves substrate-associated catalytic architecture. DHDDS provides the substrate pocket, completed by the NUS1 tail. The experiment does not establish the same activity for each natural alternative DHDDS product. Supporting Evidence: PMID:33077723
GO:0045547 ditrans,polycis-polyprenyl diphosphate synthase [(2E,6E)-farnesyl diphosphate specific] activity	IDA PMID:28842490 A conserved C-terminal RXG motif in the NgBR subunit of cis-...	ACCEPT	Summary: Both subunits contribute to the catalytically active human cis-prenyltransferase. Reason: PMID:28842490 purifies a human DHDDS–NgBR complex and tests FPP/IPP-dependent activity and mutations. The contributes_to annotation correctly captures cooperative activity. Its yeast rescue tests of natural isoforms 1, 2 and 3 have a narrower scope than a universal statement about each isoform’s activity; isoform 4 was not tested.
GO:1904423 dehydrodolichyl diphosphate synthase complex	IDA PMID:28842490 A conserved C-terminal RXG motif in the NgBR subunit of cis-...	ACCEPT	Summary: DHDDS is part of the experimentally purified human cis-prenyltransferase complex. Reason: PMID:28842490 isolates the human DHDDS–NgBR complex from Expi293F membrane preparations and demonstrates its catalytic activity. This directly supports membership. The later structures and solution assembly measurements refine its architecture, without changing the molecular identity of the complex.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4755545	ACCEPT	Summary: The disease-pathway source retains the correct ER-membrane compartment. Reason: Reactome R-HSA-4755545 uses catalyst 9631910, complex R-HSA-9631761 and component R-HSA-4755568, explicitly DHDDS K42E at the ER membrane with reference entity Q86SQ9. This is a mutant reaction model, not an independent wild-type localization experiment. The compartment is nevertheless directly supported for DHDDS by PMID:14652022; retaining the location does not transfer the mutant’s catalytic defect to wild type.
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-4419978	ACCEPT	Summary: The normal Reactome reaction places the DHDDS–NUS1 catalyst at the ER membrane. Reason: The public event R-HSA-4419978 links catalyst 4419984 to complex R-HSA-6806947 and DHDDS component R-HSA-4419977, whose reference accession is Q86SQ9 and compartment is GO:0005789. This is target-specific entity placement, corroborated by experimental localization, rather than inference from every compartment listed on the reaction.
GO:0005515 protein binding	IPI PMID:15110773 In vivo interaction between the human dehydrodolichyl diphos...	KEEP AS NON CORE	Summary: Retain the experimentally reported NPC2 interaction without assigning cholesterol transport. Reason: The PMID:15110773 abstract explicitly describes full-length human DHDDS as a yeast two-hybrid bait and confirms NPC2 association by in-vitro co-immunoprecipitation. The original full text was not recovered; those reported positive assays support retention, while native topology and physiological function remain unresolved. NPC2 is a soluble cholesterol-transfer protein, not evidence that DHDDS transports cholesterol or enables a receptor/adaptor activity. No applicable, sufficiently supported more specific binding term was established. The standing project policy retains this positive generic interaction as non-core. Supporting Evidence: PMID:15110773 further confirmed by in vitro co-immunoprecipitation experiment

Gene Description

Existing Annotations Review

Core Functions

References

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