GGPS1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004311 geranylgeranyl diphosphate synthase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred geranylgeranyl diphosphate synthase activity. This is the correct, well-supported core molecular function of GGPS1, also demonstrated experimentally by direct assay (IDA) and by disease-variant analysis (IMP). Redundant with the IDA/IMP annotations but represents the gene's own core function.
GO:0008299 isoprenoid biosynthetic process	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: GGPP synthase acts within isoprenoid biosynthesis, so this is correct. However it is a general parent of the more specific geranylgeranyl diphosphate biosynthetic process (GO:0033386); retained as a valid but non-core process term.
GO:0004161 dimethylallyltranstransferase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: EC 2.5.1.1 (DMAPP + IPP -> geranyl-PP) is one of the sequential chain-elongation activities performed by the GGPS1 active site en route to GGPP, and is documented in UniProt as a catalytic-activity reaction. This is a real activity but the physiological product/role is GGPP, not release of geranyl diphosphate; kept as non-core. Supporting Evidence: file:human/GGPS1/GGPS1-uniprot.txt Reaction=isopentenyl diphosphate + dimethylallyl diphosphate = (2E)-
GO:0004311 geranylgeranyl diphosphate synthase activity	IEA GO_REF:0000120	ACCEPT	Summary: Automated EC/RHEA-based (EC 2.5.1.29, RHEA:17653) assignment of the enzyme's core GGPP synthase activity. Correct and consistent with the experimental annotations; accepted as the core molecular function. Supporting Evidence: file:human/GGPS1/GGPS1-uniprot.txt (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate;
GO:0004337 (2E,6E)-farnesyl diphosphate synthase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: EC 2.5.1.10 (geranyl-PP + IPP -> (2E,6E)-farnesyl-PP) is another of the sequential elongation activities of the GGPS1 active site, documented as a UniProt catalytic reaction. Real, but an intermediate step rather than the physiological product; kept as non-core. Supporting Evidence: file:human/GGPS1/GGPS1-uniprot.txt Reaction=isopentenyl diphosphate + (2E)-geranyl diphosphate = (2E,6E)-
GO:0004659 prenyltransferase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro (IPR000092, polyprenyl synthase) domain-based assignment. GGPS1 is a prenyltransferase, so this is not wrong, but it is a general parent that is far less informative than the specific geranylgeranyl diphosphate synthase activity (GO:0004311); flagged as over-annotation.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping to cytoplasm. Correct: GGPS1 is a cytosolic enzyme, confirmed by immunofluorescence/immunohistochemistry (PubMed:32403198). A more general parent of cytosol; accepted as a correct location.
GO:0006720 isoprenoid metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA machine-learning assignment to isoprenoid metabolic process. Correct but a general parent of the specific GGPP biosynthetic process; also supported by IDA (PMID:10026212). Retained as valid non-core.
GO:0008299 isoprenoid biosynthetic process	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro-based assignment to isoprenoid biosynthetic process. Correct but general relative to geranylgeranyl diphosphate biosynthetic process (GO:0033386); duplicate of the IBA annotation. Kept as non-core.
GO:0030018 Z disc	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular-location keyword mapping to Z disc, derived from the immunohistochemistry in PubMed:32403198 showing prominent Z-disc localization in skeletal muscle. This is a tissue-specific/context-specific pool rather than the bulk cytosolic enzyme; kept as non-core. Supporting Evidence: PMID:32403198 GGPPS showed a prominent Z disc localization (Z disc labeled with desmin antibody) in the longitudinal section of normal human muscle biopsy
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular-location mapping to perinuclear region, derived from the immunofluorescence in PubMed:32403198 (fibroblasts showed perinuclear concentration). A context-specific pool; kept as non-core. Supporting Evidence: PMID:32403198 along with signals concentrated in some organelles and in the perinuclear region
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: IntAct-derived binary interaction (with ATOX1, O00244) from a proteome-scale high-throughput interactome screen. "Protein binding" is uninformative and there is no dedicated evidence that this heterotypic interaction reflects a specific cellular function of GGPS1; flagged as over-annotation (retained per policy, not removed). Reason: GO:0005515 protein binding conveys no information about molecular function, and the cited study (an interaction screen or incidental report) does not support a more informative activity term. Removal does not mean the interaction is false; the gene's activity is captured by its catalytic and identical-protein binding annotations.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: IntAct-derived binary interaction (with SDCBP, O00560) from the HuRI reference interactome. Uninformative bare "protein binding" from a high-throughput screen with no functional follow-up; flagged as over-annotation. Reason: GO:0005515 protein binding conveys no information about molecular function, and the cited study (an interaction screen or incidental report) does not support a more informative activity term. Removal does not mean the interaction is false; the gene's activity is captured by its catalytic and identical-protein binding annotations.
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: Self-interaction (O95749-O95749) detected in a proteome-scale interactome screen. This is biologically consistent with the obligate homohexamer (trimer of homodimers) seen in the crystal structure and gel filtration. It reflects a genuine structural property of the enzyme rather than its core catalytic function; kept as non-core. Supporting Evidence: file:human/GGPS1/GGPS1-uniprot.txt Homohexamer; trimer of homodimers.
GO:0042802 identical protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	KEEP AS NON CORE	Summary: Self-interaction from a binary-interaction screen. Same interpretation as the other GO:0042802 annotations: consistent with the homohexameric assembly, a structural property rather than the core function; kept as non-core. Supporting Evidence: file:human/GGPS1/GGPS1-uniprot.txt Homohexamer; trimer of homodimers.
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Self-interaction from the HuRI reference interactome. Consistent with the homohexamer; kept as non-core (structural, not the core catalytic MF). Supporting Evidence: file:human/GGPS1/GGPS1-uniprot.txt Homohexamer; trimer of homodimers.
GO:0033384 geranyl diphosphate biosynthetic process	IEA GO_REF:0000041	KEEP AS NON CORE	Summary: UniPathway mapping (UPA00259). Formation of geranyl diphosphate is one of the sequential condensation steps the GGPS1 active site carries out toward GGPP (EC 2.5.1.1). Real but an intermediate step rather than the defining biological role; kept as non-core.
GO:0033386 geranylgeranyl diphosphate biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: UniPathway mapping (UPA00389). This is the core biological process for GGPS1: synthesis of the C20 isoprenoid GGPP that is the lipid donor for protein geranylgeranylation. Accepted as the gene's core process.
GO:0045337 trans, trans-farnesyl diphosphate biosynthetic process	IEA GO_REF:0000041	KEEP AS NON CORE	Summary: UniPathway mapping (UPA00260) for farnesyl diphosphate biosynthesis (EC 2.5.1.10), an intermediate elongation step of GGPS1 toward GGPP. Real activity but not the defining product; kept as non-core.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas immunofluorescence localizing GGPS1 to the cytosol. This is the primary subcellular location of the enzyme and is corroborated by the disease study's cytoplasmic immunostaining; accepted as the core location.
GO:0004311 geranylgeranyl diphosphate synthase activity	IMP PMID:32403198 GGPS1 Mutations Cause Muscular Dystrophy/Hearing Loss/Ovaria...	ACCEPT	Summary: Experimental (mutation) evidence: recombinant wild-type and disease-mutant GGPS1 were assayed for GGPP synthase activity using FPP/C14-IPP as substrate, with mutants retaining ~70-85% of wild-type activity. Directly demonstrates the enzyme's core GGPP synthase activity; accepted. Supporting Evidence: PMID:32403198 We first measured enzyme activity of wild‐type and mutant GGPPS expressed in bacteria. Using 10μM farnesyl pyrophosphate (FPP)/C14‐isopentenyl pyrophosphate (C14‐IPP) as a substrate
GO:0005737 cytoplasm	IMP PMID:32403198 GGPS1 Mutations Cause Muscular Dystrophy/Hearing Loss/Ovaria...	ACCEPT	Summary: Immunostaining in the disease study showed uniform cytoplasmic expression of GGPPS in dermal fibroblasts. Correct location (general parent of cytosol); accepted. Supporting Evidence: PMID:32403198 In human dermal fibroblasts, GGPPS showed a rather uniform cytoplasmic expression
GO:0030018 Z disc	IMP PMID:32403198 GGPS1 Mutations Cause Muscular Dystrophy/Hearing Loss/Ovaria...	KEEP AS NON CORE	Summary: Immunohistochemistry showed prominent Z-disc localization of GGPPS in skeletal muscle (co-labeled with desmin). A tissue-specific/context-specific pool rather than the bulk cytosolic enzyme; kept as non-core. Supporting Evidence: PMID:32403198 GGPPS showed a prominent Z disc localization (Z disc labeled with desmin antibody) in the longitudinal section of normal human muscle biopsy
GO:0048471 perinuclear region of cytoplasm	IMP PMID:32403198 GGPS1 Mutations Cause Muscular Dystrophy/Hearing Loss/Ovaria...	KEEP AS NON CORE	Summary: Immunofluorescence showed GGPPS signal concentrated in the perinuclear region of dermal fibroblasts. Context-specific pool; kept as non-core. Supporting Evidence: PMID:32403198 along with signals concentrated in some organelles and in the perinuclear region
GO:0005829 cytosol	TAS Reactome:R-HSA-1655832	ACCEPT	Summary: Reactome-asserted cytosolic location (expression of GGPS1 event). Consistent with the IDA and IMP localization evidence; accepted.
GO:0005829 cytosol	TAS Reactome:R-HSA-9717830	ACCEPT	Summary: Reactome-asserted cytosolic location (GGPS1 hexamer transfers IPPP to GPP reaction). Consistent with primary cytosolic localization; accepted.
GO:0005829 cytosol	TAS Reactome:R-HSA-9717834	ACCEPT	Summary: Reactome-asserted cytosolic location (GGPS1 hexamer transfers IPPP to DMAPP reaction). Consistent with primary cytosolic localization; accepted.
GO:0004311 geranylgeranyl diphosphate synthase activity	IDA PMID:10026212 Human geranylgeranyl diphosphate synthase. cDNA cloning and ...	ACCEPT	Summary: Direct assay of recombinant human GGPPS expressed in E. coli showing GGPP formation (240 nmol/min/mg) from FPP and IPP. Definitive experimental evidence for the core GGPP synthase activity; accepted. Supporting Evidence: PMID:10026212 formation (240 nmol/min/mg) from FPP and isopentenyl diphosphate.
GO:0004311 geranylgeranyl diphosphate synthase activity	IDA PMID:9741684 Human geranylgeranyl diphosphate synthase: isolation of the ...	ACCEPT	Summary: Recombinant purified His-tagged human protein exhibited GGPP synthase activity, synthesizing GGPP from FPP and IPP. Independent direct experimental support for the core molecular function; accepted. Supporting Evidence: PMID:9741684 namely the synthesis of GGPP from farnesyl diphosphate and isopentenyl
GO:0006720 isoprenoid metabolic process	IDA PMID:10026212 Human geranylgeranyl diphosphate synthase. cDNA cloning and ...	KEEP AS NON CORE	Summary: Experimental demonstration that GGPS1 produces GGPP places it in isoprenoid metabolism. Correct but a general parent of the specific GGPP biosynthetic process; kept as non-core. Supporting Evidence: PMID:10026212 GGPP, which is an important molecule responsible for the C20-prenylated protein

Gene Description

Existing Annotations Review

Core Functions

References

📚 Additional Documentation

Notes

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