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Showing UBIAD1 — TERE1 is a alias.

UBIAD1

UbiA prenyltransferase domain-containing protein 1 · UniProt Q9Y5Z9

Length
338 aa
Mass
36.8 kDa
Annotated
2026-06-10
60 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBIAD1 is a membrane-embedded UbiA-family prenyltransferase that couples isoprenoid biosynthesis to sterol homeostasis (PMID:20953171, PMID:25742604). As an enzyme it synthesizes menaquinone-4 (vitamin K2/MK-4) using vitamin K derivatives and isoprenyl diphosphate side-chain donors, a reaction reconstituted in insect-cell membranes and confirmed by NMR (PMID:20953171), and it also produces non-mitochondrial CoQ10 (PMID:23374346); systematic mutagenesis defined four conserved domains governing substrate recognition, a redox CxxC motif, a catalytic hinge, and Mg2+/isoprenyl side-chain binding (PMID:25874989), and crystal structures of the archaeal homologue AfUbiA established the Mg2+-dependent prenyl-transfer mechanism with disease mutations clustering at the active site (PMID:25051182). Beyond catalysis, UBIAD1 is an ER-resident sensor of geranylgeranyl pyrophosphate (GGpp): sterols stimulate UBIAD1 binding to HMG-CoA reductase (HMGCR) to block its sterol-accelerated ERAD, and GGpp displaces UBIAD1 from HMGCR—allowing reductase degradation and triggering UBIAD1's COPII-dependent transport from ER to Golgi (PMID:25742604, PMID:23977195, PMID:27121042, PMID:34842525). UBIAD1 thus continuously cycles between ER and Golgi, with the upstream phosphatase PDP1 tuning the GGpp pool that controls this trafficking (PMID:27121042, PMID:34842525). Genetic epistasis in mice—rescue of Ubiad1-knockout embryonic lethality by ERAD-resistant HMGCR—establishes that the physiologically essential role of UBIAD1 is regulation of HMGCR ERAD rather than MK-4 synthesis (PMID:32118581, PMID:25127365). Missense mutations in UBIAD1 cause Schnyder crystalline corneal dystrophy: SCD mutants are trapped in the ER, compete with Insig-1 for HMGCR binding, constitutively block HMGCR ERAD, and drive cholesterol accumulation, a phenotype reproduced in G184R knock-in mice (PMID:17668063, PMID:17962451, PMID:31323021, PMID:30785396). UBIAD1-derived CoQ10 additionally protects cells from lipid peroxidation, supporting endothelial and acinar cell survival (PMID:23374346, PMID:23533172, PMID:31013667), and UBIAD1 restrains oncogenic signaling by retaining H-Ras in the Golgi in a GGpp-dependent manner (PMID:30518913).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2005 Medium

    Before any enzymatic role was known, UBIAD1 (TERE1) was placed in lipid/lipoprotein biology by identifying a direct protein partner.

    Evidence Bacterial two-hybrid, affinity chromatography and labelled-protein binding mapping interaction to the ApoE C-terminal domain

    PMID:15782423

    Open questions at the time
    • Functional consequence of the ApoE interaction undefined
    • No connection yet to prenyltransferase activity or cholesterol regulation
  2. 2007 Medium

    Genetic linkage established UBIAD1 as the causal gene for Schnyder crystalline corneal dystrophy, framing it as a disease-relevant prenyltransferase.

    Evidence Fine mapping, Sanger sequencing and co-segregation in multiple SCCD families, with structural modelling localizing mutations to a predicted prenyltransferase domain

    PMID:17668063 PMID:17962451

    Open questions at the time
    • Mechanism linking mutations to corneal cholesterol accumulation unknown
    • Enzymatic activity not yet demonstrated experimentally
  3. 2010 High

    The biochemical identity of UBIAD1 was resolved by demonstrating it is the MK-4 (vitamin K2) biosynthetic enzyme, localized to the ER.

    Evidence siRNA knockdown in human cells plus baculovirus reconstitution in Sf9 cells with isotope-labelled substrate conversion verified by 2H-NMR

    PMID:20953171

    Open questions at the time
    • Did not address regulation of the enzyme
    • Relationship between MK-4 synthesis and SCD pathology unresolved
  4. 2011 Medium

    UBIAD1 was tied to cellular cholesterol control and tumor suppression, hinting at a regulatory role beyond MK-4 synthesis.

    Evidence Ectopic expression/knockdown with cholesterol assays, ApoE binding, and nude-mouse xenograft tumorigenicity, plus a TBL2 interaction

    PMID:21740188

    Open questions at the time
    • Molecular mechanism of cholesterol modulation not defined
    • TBL2/ApoE roles mechanistically unconnected to enzymatic function
  5. 2013 High

    Distinct biosynthetic and survival functions emerged: UBIAD1 makes non-mitochondrial CoQ10 in the Golgi and is cell-autonomously required for endothelial survival via vitamin K2.

    Evidence Zebrafish null mutants (barolo, reddish), CoQ10/ROS measurements, eNOS epistasis, and rescue by human UBIAD1 or vitamin K2

    PMID:23374346 PMID:23533172

    Open questions at the time
    • Cardiac phenotype not rescued by vitamin K2, implying an additional pathway
    • Subcellular site reconciling ER MK-4 vs Golgi CoQ10 synthesis unclear
  6. 2014 High

    Structural and in vivo work defined the catalytic mechanism and the essential physiological output of UBIAD1.

    Evidence AfUbiA crystal structures with Mg2+/isoprenyl diphosphate plus MenA mutagenesis; mouse knockout with ES-cell biochemistry separating MK-4 from CoQ synthesis

    PMID:25051182 PMID:25127365

    Open questions at the time
    • Human full-length UBIAD1 structure not solved
    • Why knockout is embryonic lethal not yet explained by MK-4 loss
  7. 2015 High

    The defining regulatory mechanism was established: UBIAD1 is the geranylgeraniol/GGpp sensor that controls sterol-accelerated ERAD of HMGCR.

    Evidence Reciprocal co-IP, CRISPR-Cas9 knockout epistasis, pulse-chase ERAD assays, GGOH manipulation, SCD mutant panels, plus enzymological domain mapping and YY1 promoter regulation

    PMID:25742604 PMID:25772619 PMID:25874989

    Open questions at the time
    • Structural basis of GGpp-induced displacement not visualized
    • How sterols promote the UBIAD1-HMGCR interaction at the molecular level unresolved
  8. 2016 High

    UBIAD1 trafficking was shown to be a dynamic GGpp-gated cycle between ER and Golgi, with ER trapping as the disease-relevant state.

    Evidence Subcellular fractionation, immunofluorescence and ERAD assays under GGOH manipulation; SCD mutants constitutively ER-sequestered; PDP1 gain/loss-of-function

    PMID:27121042 PMID:34842525

    Open questions at the time
    • Identity of the GGpp-binding-coupled conformational switch driving export unknown
    • COPII machinery specificity for UBIAD1 cargo not detailed
  9. 2019 High

    In vivo knock-in mice and mass spectrometry confirmed that SCD mutants block HMGCR ERAD by competing with Insig-1, causing tissue HMGCR accumulation and SCD-like corneal cholesterol deposits.

    Evidence MS co-IP identifying HMGCR, Ubiad1 G184R/SCD knock-in mice, ERAD assays, corneal histology and cholesterol measurement

    PMID:30785396 PMID:31323021

    Open questions at the time
    • Tissue specificity of corneal pathology despite systemic HMGCR accumulation unexplained
    • Insig-1 vs UBIAD1 binding interface on HMGCR not structurally defined
  10. 2020 High

    Genetic epistasis proved that HMGCR ERAD regulation, not MK-4 synthesis, is the essential function of UBIAD1.

    Evidence Rescue of Ubiad1-knockout embryonic lethality by ERAD-resistant HMGCR knock-in; cell-free MK-4 assays showing reduced GGpp affinity of SCD mutants and autophagy protection of ER-trapped protein

    PMID:32118581 PMID:32188638

    Open questions at the time
    • Why mevalonate-pathway depletion is lethal at this developmental stage not pinpointed
    • Link between autophagy escape and SCD severity in vivo untested
  11. 2022 Medium

    UBIAD1-derived plasma-membrane CoQ10 was shown to be a determinant of cancer cell survival and biophysical state via protection from lipid peroxidation.

    Evidence Knockdown/overexpression in melanoma and breast cancer with CoQ10 and lipid peroxidation assays, NQO1 epistasis, atomic force microscopy of membrane stiffness, and in vivo metastasis models

    PMID:35255427 PMID:39294175

    Open questions at the time
    • Whether membrane CoQ10 role depends on UBIAD1 trafficking state unknown
    • Context-dependent tumor-suppressive vs pro-survival roles not reconciled
  12. 2025 Medium

    Pharmacological rescue of SCD mutant trafficking was demonstrated, establishing UBIAD1 ER-to-Golgi transport as a druggable target.

    Evidence Chemical genetic screen identifying Apatinib, immunofluorescence rescue of N102S Golgi localization, HMGCR ERAD restoration, and photoaffinity-labeling showing direct UBIAD1 binding independent of kinase inhibition

    PMID:40372435

    Open questions at the time
    • Allosteric binding site on UBIAD1 not mapped
    • Not independently replicated; efficacy in SCD models untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GGpp binding is structurally transduced into UBIAD1's conformational switch between HMGCR-bound ER retention and Golgi export remains unresolved at atomic resolution for the human protein.
  • No full-length human UBIAD1 structure in ligand-bound or HMGCR-complexed states
  • Molecular determinants of sterol-stimulated HMGCR binding undefined
  • Reconciliation of dual MK-4 (ER) and CoQ10 (Golgi/plasma membrane) catalytic activities with trafficking incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0140299 molecular sensor activity 3 GO:0008289 lipid binding 2
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005794 Golgi apparatus 4 GO:0005886 plasma membrane 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-1430728 Metabolism 3 R-HSA-5653656 Vesicle-mediated transport 2
Partners
APOEHMGCRHRASINSIG1SOAT1TBL2

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 UBIAD1 (human homologue of E. coli prenyltransferase menA) is a menaquinone-4 (MK-4) biosynthetic enzyme: siRNA knockdown inhibited conversion of deuterium-labelled vitamin K derivatives to MK-4-d7 in human cells, and baculovirus-expressed UBIAD1 in insect cells catalyzed this conversion; the product was confirmed by 2H-NMR. UBIAD1 was localized to the endoplasmic reticulum. siRNA knockdown in human cells, baculovirus expression in Sf9 insect cells, isotope-labelled substrate conversion assay, 2H-NMR chemical identification, immunofluorescence localization Nature High 20953171
2013 Human UBIAD1 is a non-mitochondrial prenyltransferase that synthesizes CoQ10 in the Golgi membrane compartment. Loss of UBIAD1 (zebrafish barolo null mutant) reduces the cytosolic pool of CoQ10, causing ROS-mediated lipid peroxidation in vascular cells and cardiovascular failure. Inhibition of eNOS prevents Ubiad1-dependent cardiovascular oxidative damage, placing UBIAD1-derived CoQ10 upstream of eNOS/NO signaling. Zebrafish null mutant (barolo), CoQ10 measurement, ROS/lipid peroxidation assays, eNOS inhibitor epistasis, human UBIAD1 CoQ10 synthesis assay in cells Cell High 23374346
2007 Missense mutations in UBIAD1 (encoding a predicted prenyltransferase) are causal for Schnyder crystalline corneal dystrophy (SCCD). Five disease-segregating mutations were identified; UBIAD1 was reported to interact physically with apolipoprotein E. Fine mapping, Sanger sequencing in SCCD families, co-segregation analysis, bacterial two-hybrid/interaction assay (ApoE binding reported from prior work cited) PloS one Medium 17668063
2007 Nonsynonymous mutations in UBIAD1 (N102S and G177R) cause SCCD; predicted structural modelling indicated mutations affect a prenyl-transferase domain and transmembrane helices important for catalytic function. PCR-based DNA sequencing of six SCCD families, co-segregation analysis, protein structure prediction Investigative ophthalmology & visual science Medium 17962451
2014 Crystal structures of the UBIAD1 archaeal homologue AfUbiA (solved in unliganded form and bound to Mg2+ and two different isoprenyl diphosphates) revealed a Mg2+-dependent prenyl transfer mechanism. Functional assays on E. coli MenA confirmed the importance of residues involved in Mg2+ and substrate binding. Disease-causing UBIAD1 mutations cluster around the active site in AfUbiA, indicating conserved catalytic mechanism. X-ray crystallography (AfUbiA structures), site-directed mutagenesis of MenA, in vitro enzyme activity assays PLoS biology High 25051182
2015 Sterols stimulate binding of UBIAD1 to ER-localized HMG CoA reductase, inhibiting its sterol-accelerated ERAD. Geranylgeraniol (GGOH, convertible to GGpp) inhibits UBIAD1–reductase binding, allowing reductase degradation and promoting UBIAD1 transport from ER to Golgi. CRISPR-Cas9 knockout of UBIAD1 relieved the GGOH requirement for reductase degradation. SCD-associated UBIAD1 mutations block GGpp-induced displacement from reductase, preventing its degradation and identifying UBIAD1 as the target of geranylgeraniol in reductase ERAD regulation. Co-immunoprecipitation, CRISPR-Cas9 knockout, pulse-chase ERAD assay, GGOH addition/depletion, SCD mutant panel eLife High 25742604
2015 Enzymological characterization of UBIAD1 in microsomal fractions: optimal activity at pH 8.5–9.0 with DTT; geranyl pyrophosphate and farnesyl pyrophosphate are accepted as side-chain substrates; lipophilic statins directly inhibit UBIAD1 enzymatic activity. Four conserved domains are essential for activity: domain I is a substrate recognition site, domain II contains a redox CxxC motif, domain III is a catalytic hinge region, and domain IV is a Mg2+/isoprenyl side-chain binding site — established by mutagenesis of each domain. In vitro MK-4 biosynthesis assay using microsomal fractions from Sf9 cells, site-directed mutagenesis of conserved domains and individual residues, statin inhibition assay PloS one High 25874989
2012 UBIAD1 physically interacts with HMGCR (HMG CoA reductase) and SOAT1 (acyl-CoA:cholesterol acyltransferase), demonstrated by yeast two-hybrid screening and co-immunoprecipitation. SCD-associated UBIAD1 mutations reduce MK-4 synthesis and alter binding to these cholesterol metabolic enzymes. Molecular docking suggested cholesterol binds in the UBIAD1 substrate-binding cleft, overlapping with GGPP binding. Yeast two-hybrid, co-immunoprecipitation, MK-4 synthesis assay in SCD mutants, molecular docking simulation Human mutation Medium 23169578
2013 UBIAD1 is localized to the Golgi and ER (not plasma membrane) in multiple human cell lines. The N-terminal RPWS motif (Arginine finger) serves as a Golgi retention signal identified by site-directed mutagenesis. UBIAD1 is transported from ER to Golgi via a COPII-mediated mechanism (shown by brefeldin A and cycloheximide assays). Mutation of the RPWS motif reduces UBIAD1-induced apoptosis in T24 bladder cancer cells, linking Golgi localization to tumor-suppressor activity. Fluorescence microscopy, immunohistochemistry, subcellular fractionation/western blot, site-directed mutagenesis of RPWS motif, brefeldin A and cycloheximide inhibition assays, flow cytometry apoptosis assay PloS one Medium 23977195
2016 UBIAD1 continuously cycles between the ER and medial-trans Golgi in isoprenoid-replete cells. When intracellular GGpp declines, UBIAD1 becomes trapped in the ER where it inhibits HMGCR ERAD. SCD-associated mutants are constitutively sequestered in the ER and block reductase degradation. Overexpression of PDP1 (Type 1 polyisoprenoid diphosphate phosphatase), which dephosphorylates GGpp, abolishes GGOH-induced ERAD of reductase and Golgi transport of UBIAD1; conversely, PDP1 deletion enhances these reactions. Subcellular fractionation, immunofluorescence, ERAD pulse-chase assay, GGOH treatment, SCD mutant analysis Journal of lipid research High 27121042 34842525
2019 SCD-associated UBIAD1 mutants reside mainly in the ER and compete with Insig-1 for HMGCR binding, thereby preventing HMGCR ERAD and increasing cholesterol biosynthesis. HMGCR was identified as a UBIAD1 binding partner by mass spectrometry. Heterozygous Ubiad1 G184R knock-in mice accumulate elevated HMGCR protein in tissues, and aged knock-in mice exhibit corneal opacification and free cholesterol accumulation, phenocopying SCD. Mass spectrometry co-IP, co-immunoprecipitation, HMGCR ERAD assay, Ubiad1 G184R knock-in mouse model, corneal histology and cholesterol measurement PLoS genetics High 31323021
2019 Knockin mice expressing SCD-associated UBIAD1 accumulate HMGCR protein across multiple tissues due to ER sequestration of mutant UBIAD1 and inhibition of HMGCR ERAD. Aged knockin mouse corneas show opacification and sterol overaccumulation, establishing the physiological significance of UBIAD1-regulated HMGCR ERAD in cholesterol homeostasis and SCD pathogenesis. UBIAD1 SCD knock-in mouse model, HMGCR protein quantification across tissues, ERAD assay, corneal lipid analysis, histology eLife High 30785396
2020 Embryonic lethality of Ubiad1 homozygous knockout in mice results from enhanced ERAD of HMGCR (depleting mevalonate-derived products), not from reduced MK-4 synthesis: homozygous Ubiad1 deletion is rescued in knockin mice expressing ubiquitination/ERAD-resistant HMGCR, providing genetic epistasis evidence for UBIAD1 as a physiological regulator of HMGCR ERAD. Genetic epistasis — Ubiad1 KO crossed with ERAD-resistant HMGCR knockin mice, embryonic lethal rescue experiment eLife High 32118581
2020 SCD-associated UBIAD1 exhibits reduced MK-4 synthetic activity in isolated membranes and intact cells (biochemical assay developed in this study), likely due to reduced affinity for GGpp. ER sequestration of SCD-associated UBIAD1 protects it from autophagy-mediated degradation, allowing intracellular accumulation that amplifies inhibition of HMGCR ERAD. Cell-free membrane MK-4 synthesis assay, intact-cell MK-4 assay, autophagy inhibitor treatment, SCD mutant panel analysis Journal of lipid research High 32188638
2013 UBIAD1-mediated vitamin K2 synthesis is required cell-autonomously for endothelial cell survival and vascular homeostasis in zebrafish: the reddish/reh ubiad1 mutant exhibits cardiac edema, cranial hemorrhages and vascular degeneration due to endothelial cell survival defects. Vascular (but not cardiac) phenotype was rescued by zebrafish or human UBIAD1 or by exogenous vitamin K2; warfarin-treated zebrafish phenocopy the vascular defect, suggesting an alternative UBIAD1/vitamin K-independent pathway regulates cardiac function. Zebrafish forward genetic screen, transgenic rescue with zebrafish and human UBIAD1, vitamin K2 supplementation rescue, warfarin pharmacological phenocopy Development (Cambridge, England) High 23533172
2014 Ubiad1-deficient mouse embryos die by E7.5 with gastrulation arrest. Ubiad1−/− ES cells cannot synthesize vitamin K2 but retain CoQ9 synthesis at wild-type levels, indicating UBIAD1 is responsible for MK-4 but not CoQ9 synthesis in mice. Embryonic lethality was partially extended by maternal MK-4 or CoQ10 supplementation. Gene targeting/knockout in mice, ES cell vitamin K2 and CoQ9 synthesis assays, maternal supplementation rescue PloS one High 25127365
2011 TERE1/UBIAD1 and the interacting protein TBL2 inversely modulate cellular cholesterol levels (20–50% change) in HEK293 and bladder cancer cells. TERE1 point mutations associated with SCCD affect ApoE binding and result in cholesterol levels distinct from wild-type. Ectopic TERE1 expression in J82 bladder cancer cells dramatically inhibits nude mouse tumorigenesis. Ectopic expression and siRNA knockdown of TERE1/TBL2, Amplex Red cholesterol assay, GST-ApoE binding assay, molecular modeling, nude mouse xenograft tumorigenicity assay DNA and cell biology Medium 21740188
2005 TERE1/UBIAD1 physically interacts with the C-terminal domain (from aa 124) of apolipoprotein E (ApoE), confirmed by bacterial two-hybrid screening, ProBond affinity chromatography with 6xHis-tagged recombinant proteins, and 35S-labelled protein binding. Bacterial two-hybrid screening, ProBond affinity chromatography, 35S-Met/Cys labelled protein binding assay Journal of cellular biochemistry Medium 15782423
2013 TERE1/UBIAD1 directly interacts with the mitochondrial WD40-repeat protein TBL2 with high affinity (demonstrated by biochemical binding assays). SCD-associated single amino acid substitutions in TERE1 reduce TBL2 binding. Ectopic TERE1 expression elevates mitochondrial trans-membrane potential, oxidative stress, NO production, and activates SXR nuclear hormone receptor target genes. Biochemical binding assays (direct high-affinity interaction), immunoprecipitation, mitochondrial membrane potential measurement, ROS/NO assays, RT-PCR of SXR target genes, subcellular fractionation Journal of cellular biochemistry Medium 23564352
2018 UBIAD1 interacts with the C-terminal domain of H-Ras, retains H-Ras in the Golgi apparatus, and prevents its trafficking from Golgi to the plasma membrane, thereby blocking aberrant Ras/MAPK signaling and inhibiting bladder cancer cell proliferation. GGpp is required for UBIAD1 to maintain this function. Drosophila HEIX (UBIAD1 ortholog) in vivo model confirmed that Ras/ERK activation at the plasma membrane (by UBIAD1 loss) induced melanotic masses. Co-immunoprecipitation, subcellular fractionation, live-cell imaging of H-Ras trafficking, Ras/ERK signaling assays, GGpp supplementation/depletion, Drosophila in vivo model Cell death & disease Medium 30518913
2015 The transcription factor YY1 positively regulates UBIAD1 expression by binding to a YY1 consensus motif in the UBIAD1 promoter; demonstrated by deletion/mutation analysis of the promoter, EMSA, and chromatin immunoprecipitation. YY1 siRNA knockdown decreased endogenous UBIAD1 mRNA and MK-4 conversion activity. Promoter deletion/mutation analysis, EMSA (electrophoretic mobility shift assay), chromatin immunoprecipitation (ChIP), siRNA knockdown, MK-4 conversion activity assay Biochemical and biophysical research communications Medium 25772619
2021 Type 1 polyisoprenoid diphosphate phosphatase (PDP1) dephosphorylates GGpp to GGOH, thereby modulating the intracellular GGpp pool. PDP1 overexpression abolishes protein geranylgeranylation, GGOH-induced ERAD of HMGCR, and Golgi transport of UBIAD1; PDP1 deletion enhances these reactions, establishing PDP1 as an upstream regulator of the GGpp-sensing mechanism that controls UBIAD1 trafficking. PDP1 overexpression and knockout cells, protein geranylgeranylation assay, HMGCR ERAD pulse-chase, UBIAD1 Golgi localization by immunofluorescence eLife High 34842525
2021 Cell-based assays showed that UBIAD1 SCD mutations differentially affect MK-4 biosynthesis and vitamin K-dependent (VKD) carboxylation: hotspot N102S retains ~82% MK-4 activity and does not affect VKD carboxylation, while G186R significantly impairs both. CRISPR-Cas9 knockout of endogenous Ubiad1 in reporter cells established the assay system. CRISPR-Cas9 Ubiad1 KO reporter cells, MK-4 production assay, VKD carboxylation efficiency assay, SCD mutant panel The FEBS journal Medium 34813684
2025 Chemical genetic screening identified the tyrosine kinase inhibitor Apatinib as a molecule that restores Golgi localization of SCD-associated UBIAD1 (N102S) and thereby relieves inhibition of HMGCR ERAD. This effect requires GGpp but is independent of Apatinib's tyrosine kinase inhibition. Photoaffinity labeling studies showed Apatinib binds directly to UBIAD1, indicating allosteric activation of GGpp-induced ER-to-Golgi transport. Chemical genetic screen, immunofluorescence of UBIAD1 localization, HMGCR ERAD assay, photoaffinity labeling, GGpp requirement testing, kinase inhibition control Proceedings of the National Academy of Sciences of the United States of America Medium 40372435
2019 Tamoxifen-inducible systemic UBIAD1 knockout in adult mice causes death within ~60 days, with the pancreas showing the most prominent pathology: pancreatic acinar cells disappear and are replaced by adipocytes. UBIAD1 deficiency in acinar cells increases oxidative stress and autophagy, leading to apoptotic cell death. Tamoxifen-inducible systemic UBIAD1 knockout mouse, histology, oxidative stress assays, autophagy markers, apoptosis assays International journal of molecular sciences Medium 31013667
2010 In SCD patient-derived keratocytes and lymphoblastoid cell lines, both wild-type and N102S UBIAD1 protein localize to mitochondria (by immunohistochemistry with UBIAD1-specific antibody); no significant alteration of cholesterol metabolite ratios was observed in patient versus control cell extracts. Immunohistochemistry in patient-derived keratocytes and lymphoblastoid cell lines, cholesterol metabolite analysis PloS one Low 20505825
2024 UBIAD1 and CoQ10 increase plasma membrane fluidity and cell stiffness in breast cancer cells. Loss of UBIAD1 impairs ECM-mediated oncogenic signaling and reduces ferroptosis resistance. In vivo, UBIAD1 expression in breast cancer limits circulating tumor cell survival and lung metastasis formation. Atomic force microscopy (cell stiffness), membrane fluidity assay, ferroptosis assay, ECM signaling assays, mouse xenograft/metastasis model, patient data correlation Nature communications Medium 39294175
2022 UBIAD1 and plasma membrane CoQ10 sustain melanoma cell survival and proliferation by preventing lipid peroxidation. NQO1 (NAD(P)H Quinone Dehydrogenase 1), which reduces CoQ10 on plasma membranes, acts downstream of UBIAD1 to support melanoma cell survival. UBIAD1 knockdown/overexpression in melanoma cells, CoQ10 measurement, lipid peroxidation assay, NQO1 epistasis experiment, cell viability assay Redox biology Medium 35255427

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature 258 20953171
2013 Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis. Cell 172 23374346
2007 Mutations in the UBIAD1 gene, encoding a potential prenyltransferase, are causal for Schnyder crystalline corneal dystrophy. PloS one 95 17668063
2014 Structure of a membrane-embedded prenyltransferase homologous to UBIAD1. PLoS biology 89 25051182
2007 Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy. Investigative ophthalmology & visual science 86 17962451
2015 The prenyltransferase UBIAD1 is the target of geranylgeraniol in degradation of HMG CoA reductase. eLife 73 25742604
2012 The UBIAD1 prenyltransferase links menaquinone-4 [corrected] synthesis to cholesterol metabolic enzymes. Human mutation 59 23169578
2010 UBIAD1 mutation alters a mitochondrial prenyltransferase to cause Schnyder corneal dystrophy. PloS one 51 20505825
2022 UBIAD1 alleviates ferroptotic neuronal death by enhancing antioxidative capacity by cooperatively restoring impaired mitochondria and Golgi apparatus upon cerebral ischemic/reperfusion insult. Cell & bioscience 48 35379328
2015 Functional characterization of the vitamin K2 biosynthetic enzyme UBIAD1. PloS one 48 25874989
2013 UBIAD1-mediated vitamin K2 synthesis is required for vascular endothelial cell survival and development. Development (Cambridge, England) 45 23533172
2011 The bladder tumor suppressor protein TERE1 (UBIAD1) modulates cell cholesterol: implications for tumor progression. DNA and cell biology 43 21740188
2008 Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function. American journal of medical genetics. Part A 40 18176953
2001 Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder. Oncogene 38 11314041
2014 Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice. PloS one 37 25127365
2013 The tumor suppressor TERE1 (UBIAD1) prenyltransferase regulates the elevated cholesterol phenotype in castration resistant prostate cancer by controlling a program of ligand dependent SXR target genes. Oncotarget 36 23919967
2005 An interaction between apolipoprotein E and TERE1 with a possible association with bladder tumor formation. Journal of cellular biochemistry 33 15782423
2003 TERE1, a novel gene affecting growth regulation in prostate carcinoma. The Prostate 33 12497587
2007 Identification of mutations in UBIAD1 following exclusion of coding mutations in the chromosome 1p36 locus for Schnyder crystalline corneal dystrophy. Molecular vision 30 17960116
2016 Geranylgeranyl-regulated transport of the prenyltransferase UBIAD1 between membranes of the ER and Golgi. Journal of lipid research 28 27121042
2020 MiR-4644 is upregulated in plasma exosomes of bladder cancer patients and promotes bladder cancer progression by targeting UBIAD1. American journal of translational research 26 33194029
2022 UBIAD1 and CoQ10 protect melanoma cells from lipid peroxidation-mediated cell death. Redox biology 25 35255427
2013 A novel Golgi retention signal RPWS for tumor suppressor UBIAD1. PloS one 24 23977195
2013 Ectopic expression of the TERE1 (UBIAD1) protein inhibits growth of renal clear cell carcinoma cells: altered metabolic phenotype associated with reactive oxygen species, nitric oxide and SXR target genes involved in cholesterol and lipid metabolism. International journal of oncology 23 23759948
2013 The TERE1 protein interacts with mitochondrial TBL2: regulation of trans-membrane potential, ROS/RNS and SXR target genes. Journal of cellular biochemistry 21 23564352
2020 Olfactory Mucosa Mesenchymal Stem Cells Ameliorate Cerebral Ischemic/Reperfusion Injury Through Modulation of UBIAD1 Expression. Frontiers in cellular neuroscience 20 33281557
2019 Schnyder corneal dystrophy-associated UBIAD1 mutations cause corneal cholesterol accumulation by stabilizing HMG-CoA reductase. PLoS genetics 19 31323021
2020 Enhanced ER-associated degradation of HMG CoA reductase causes embryonic lethality associated with Ubiad1 deficiency. eLife 18 32118581
2019 Schnyder corneal dystrophy-associated UBIAD1 inhibits ER-associated degradation of HMG CoA reductase in mice. eLife 18 30785396
2018 UBIAD1 protects against oxygen-glucose deprivation/reperfusion-induced multiple subcellular organelles injury through PI3K/AKT pathway in N2A cells. Journal of cellular physiology 17 29663377
2020 Schnyder corneal dystrophy-associated UBIAD1 is defective in MK-4 synthesis and resists autophagy-mediated degradation. Journal of lipid research 15 32188638
2018 UBIAD1 suppresses the proliferation of bladder carcinoma cells by regulating H-Ras intracellular trafficking via interaction with the C-terminal domain of H-Ras. Cell death & disease 15 30518913
2010 Newly reported p.Asp240Asn mutation in UBIAD1 suggests central discoid corneal dystrophy is a variant of Schnyder corneal dystrophy. Cornea 15 20489584
2024 Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer. Nature communications 13 39294175
2016 Role of UBIAD1 in Intracellular Cholesterol Metabolism and Vascular Cell Calcification. PloS one 13 26890002
2021 Type 1 polyisoprenoid diphosphate phosphatase modulates geranylgeranyl-mediated control of HMG CoA reductase and UBIAD1. eLife 12 34842525
2018 Schnyder corneal dystrophy and associated phenotypes caused by novel and recurrent mutations in the UBIAD1 gene. BMC ophthalmology 12 30223810
2011 Schnyder Corneal Dystrophy in a Saudi Arabian Family with Heterozygous UBIAD1 Mutation (p.L121F). Middle East African journal of ophthalmology 12 21572737
2009 A novel UBIAD1 mutation identified in a Chinese family with Schnyder crystalline corneal dystrophy. Molecular vision 12 19649163
2009 Surgical management and genetic analysis of a Chinese family with the S171P mutation in the UBIAD1 gene, the gene for Schnyder corneal dystrophy. The British journal of ophthalmology 11 19429578
2019 UBIAD1 Plays an Essential Role in the Survival of Pancreatic Acinar Cells. International journal of molecular sciences 10 31013667
2010 Down-regulation of TERE1/UBIAD1 activated Ras-MAPK signalling and induced cell proliferation. Cell biology international reports 10 23119142
2022 UBIAD1 effectively alleviated myocardial ischemia reperfusion injury by activating SIRT1/PGC1α. Perfusion 8 35491985
2016 Identification of the First De Novo UBIAD1 Gene Mutation Associated with Schnyder Corneal Dystrophy. Journal of ophthalmology 8 27382485
2011 A mutation in the UBIAD1 gene in a Han Chinese family with Schnyder corneal dystrophy. Molecular vision 8 22065921
2018 Clinical diversity in patients with Schnyder corneal dystrophy-a novel and known UBIAD1 pathogenic variants. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 7 30084067
2015 YY1 positively regulates human UBIAD1 expression. Biochemical and biophysical research communications 7 25772619
2021 Functional study of SCCD pathogenic gene UBIAD1 (Review). Molecular medicine reports 5 34368857
2018 UBIAD1 expression is associated with cardiac hypertrophy in spontaneously hypertensive rats. Molecular medicine reports 4 30483777
2021 Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation. The FEBS journal 3 34813684
2018 Long-Term Outcome After Penetrating Keratoplasty in a Pedigree With the G177E Mutation in the UBIAD1 Gene for Schnyder Corneal Dystrophy. Cornea 3 29319599
2018 Effect of Coenzyme Q10 on Expression of UbiAd1 Gene in Rat Model of Local Cerebral Ischemia. Bulletin of experimental biology and medicine 3 29797120
2012 [Mutation in the UBIAD1 gene of a Chinese family with Schnyder crystal corneal dystrophy]. Zhonghua yi xue za zhi 2 23328470
2025 Hepatic lipid metabolism is altered in Ubiad1+/- mice of both sexes. Scientific reports 1 40016272
2025 Allosteric regulation of UBIAD1 trafficking from ER to Golgi revealed by chemical genetic screening. Proceedings of the National Academy of Sciences of the United States of America 1 40372435
2026 Mesenchymal stem cell-originated exosomal ZEB1 alleviates hypoxia/reperfusion-induced apoptosis, oxidative stress, and endoplasmic reticulum stress in cardiomyocytes via regulating UBIAD1. Journal of bioenergetics and biomembranes 0 41849074
2025 Cloning and functional analysis of the TERE1 gene using the Gal4-UaS system in S2 cells: A streamlined approach for human gene functional genomics. Journal, genetic engineering & biotechnology 0 40854644
2024 Vitamin K converting enzyme UBIAD1 plays an important role in osteogenesis and chondrogenesis in mice. Biochemical and biophysical research communications 0 38335702
2022 UbiA prenyltransferase domain-containing protein 1 (UBIAD1) variant c.695 A > G identified in a multigenerational Japanese family with Schnyder corneal dystrophy. Japanese journal of ophthalmology 0 36367598
2022 UBIAD1 protects against oxygen-glucose deprivation/reoxygenation injury via nNOS/NO pathway. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 0 36411684

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