Affinage

Showing CERT1 — COL4A3BP is a alias.

CERT1

Ceramide transfer protein · UniProt Q9Y5P4

Length
624 aa
Mass
70.8 kDa
Annotated
2026-06-09
62 papers in source corpus 33 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: UniProt preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CERT1 (CERT/STARD11/GPBP) is a cytosolic lipid-transfer protein that drives non-vesicular delivery of ceramide from the endoplasmic reticulum to the Golgi for sphingomyelin synthesis (PMID:15596449, PMID:16895911). Its START domain extracts and stereospecifically binds a single D-erythro ceramide within an amphiphilic cavity whose size sets an acyl-chain-length limit, with the Omega1 loop and Trp473 acting as a gate for lipid loading and release (PMID:15596449, PMID:18184806, PMID:20036255). Spatial coupling of this intrinsically random transfer activity is achieved by two targeting modules: a FFAT motif that binds the ER-resident proteins VAP-A/VAP-B and a PH domain that recognizes Golgi PI4P through a basic groove, positioning CERT at ER–Golgi membrane contact sites (PMID:16895911, PMID:22869376); CERT preferentially consumes the distal-Golgi PI4P pool generated by a C10orf76–PI4KB axis where sphingomyelin synthesis occurs (PMID:37195633). CERT activity is governed by a phosphorylation feedback loop: multisite serine-repeat-motif (SRM) phosphorylation, primed by diacylglycerol-activated PKD, drives an autoinhibitory intramolecular SRM–PH interaction that competes with PI4P binding and silences transfer, while the ER phosphatase PP2Cepsilon reactivates CERT in a VAP-dependent manner, and phosphorylation at S315 adjacent to the FFAT motif independently enhances VAP binding to activate the protein (PMID:17442665, PMID:18165232, PMID:24569996, PMID:29848549, PMID:35409383). Beyond canonical sphingomyelin production, CERT supplies ceramide for multivesicular-body/extracellular-vesicle biogenesis at ER–MVB contact sites and transfers alkylacylglycerol for ether phospholipid synthesis (PMID:35421371, PMID:38110110), and targeted ER-to-mitochondria ceramide transport commits cells to Bax-dependent apoptosis (PMID:27888218). De novo gain-of-function CERT1 missense variants causing intellectual disability cluster in regulatory regions—including the SRM and a dimeric helical domain—where they impair SRM hyperphosphorylation-dependent autoinhibition, producing unchecked sphingolipid production that is corrected by pharmacological CERT inhibition in a Drosophila model (PMID:33347465, PMID:34688657, PMID:36976648). CERT is also co-opted by intracellular pathogens, with Chlamydia IncD and HSV-1 pUL21 binding CERT domains directly to redirect or activate ceramide trafficking (PMID:21731489, PMID:21909260, PMID:36243114).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2004 High

    Established that CERT is a bona fide ceramide carrier, defining its core biochemical activity and substrate selectivity.

    Evidence Cell-free lipid transfer and binding assays with radiolabeled ceramide analogs

    PMID:15596449

    Open questions at the time
    • Did not resolve how the random transfer activity is spatially organized in cells
    • Structural basis of stereospecificity not yet defined
  2. 2006 High

    Resolved how CERT's intrinsically directionless transfer is harnessed for vectorial ER-to-Golgi transport, showing the FFAT (VAP) and PH (PI4P) modules spatially constrain the START domain.

    Evidence Co-IP with VAP-A/B, FFAT mutagenesis, semi-intact cell transport and cell-free transfer assays

    PMID:16895911

    Open questions at the time
    • Did not address how the two targeting events are coordinated dynamically
    • Regulation of the cycle unknown
  3. 2007 High

    Defined the principal off-switch—SRM phosphorylation causing autoinhibitory PH–START interaction—and linked it to sphingolipid-sensing feedback.

    Evidence In vitro phosphorylation, domain interaction, PI4P/transfer assays, sphingomyelin-depletion cell experiments; PP2Cepsilon reactivation by yeast two-hybrid, Co-IP and knockdown; PH domain PI4P specificity

    PMID:17314061 PMID:17442665 PMID:18165232

    Open questions at the time
    • Kinase priming the SRM not yet identified
    • Structural basis of SRM–PH competition unresolved
  4. 2008 High

    Provided the structural mechanism for stereospecific ceramide recognition and chain-length cutoff, revealing a gated hydrophobic cavity.

    Evidence X-ray structures of apo and ceramide-bound START domain across multiple acyl chains

    PMID:18184806

    Open questions at the time
    • Dynamics of the proposed alpha-3/Omega1 gate not directly observed
    • Membrane-engagement step not captured
  5. 2008 Medium

    Identified a stress-induced oligomeric off-state, showing UVB triggers a CERT homotrimer with reduced ceramide binding via the middle region.

    Evidence Western blot, mass spectrometry, ceramide binding assay, knockdown and HPA-12 in keratinocytes

    PMID:18411267

    Open questions at the time
    • Single lab
    • Physiological trigger beyond UVB and structural basis of the trimer not defined
  6. 2009 High

    Captured the gating conformational change underlying ceramide loading/unloading by structurally trapping inhibitor-bound START with Trp473 repositioned.

    Evidence X-ray crystallography of HPA-bound START plus SPR on Trp473 membrane interaction

    PMID:20036255

    Open questions at the time
    • Membrane-coupled release step inferred, not directly visualized
    • Kinetics of gating unresolved
  7. 2011 High

    Revealed that pathogens hijack CERT, with Chlamydia IncD directly binding the PH domain to recruit CERT to inclusion membrane contact sites for development.

    Evidence Co-IP, ectopic expression, knockdown, colocalization and bacterial development assays, replicated in two labs

    PMID:21731489 PMID:21909260

    Open questions at the time
    • Did not quantify ceramide flux redirected to the inclusion
    • Whether IncD competes with native PI4P targeting unknown
  8. 2012 High

    Defined the PH-domain structural determinant of Golgi targeting—a basic groove adjacent to the PI4P site required for membrane recognition.

    Evidence Solution NMR structure, chemical-shift binding assays, cell-based mutant localization

    PMID:22869376

    Open questions at the time
    • Interplay between basic groove and SRM autoinhibition not addressed here
  9. 2014 High

    Identified an activating phosphorylation arm (S315) that enhances VAP binding and transport, showing CERT is regulated by both off- and on-switches.

    Evidence Semi-intact cell transport, Co-IP, phosphomimetic mutants, imaging under sphingolipid depletion

    PMID:24569996

    Open questions at the time
    • Kinase responsible for S315 phosphorylation not identified
    • Spatial scope of activation not yet resolved
  10. 2016 High

    Demonstrated a direct apoptotic consequence of ceramide trafficking by rerouting CERT-delivered ceramide to mitochondria.

    Evidence Engineered mitoCERT, domain/FFAT mutants, HPA-12, ceramide-synthesis inhibition, mitochondrial ceramidase, death assays

    PMID:27888218

    Open questions at the time
    • Whether endogenous CERT physiologically delivers ceramide to mitochondria not established
    • Engineered anchor may not reflect native targeting
  11. 2018 High

    Provided the structural mechanism of SRM autoinhibition, showing hyperphosphorylated SRM electrostatically competes with PI4P binding on the PH domain.

    Evidence Solution NMR, PI4P-binding assay, Golgi-targeting imaging of 10E variant

    PMID:29848549

    Open questions at the time
    • Quantitative contribution to START autoinhibition not separated
    • Dynamics in full-length protein not resolved
  12. 2018 Medium

    Extended CERT's role to extracellular vesicle biology and lipotoxic/metabolic control, linking ceramide transfer to EV biogenesis and insulin signaling.

    Evidence STARD11 knockout with EV/ceramide/viability readouts; CERT knockdown/overexpression in muscle with insulin signaling and caspase inhibition

    PMID:29759974 PMID:30139741

    Open questions at the time
    • Single labs
    • Direct lipid-transfer requirement for EV phenotype not dissected from indirect ceramide accumulation
  13. 2021 Medium

    Linked CERT1 directly to human disease, identifying de novo gain-of-function variants impairing SRM autoregulation as causes of intellectual disability.

    Evidence Exome sequencing plus biochemical SRM-phosphorylation and localization analysis, with a non-impairing variant as negative control

    PMID:33347465 PMID:34688657

    Open questions at the time
    • Single lab functional studies
    • Mechanism linking sphingolipid dysregulation to neurodevelopmental phenotype not defined
  14. 2022 Medium

    Mapped additional regulatory elements of autoinhibition and showed the activating and inhibitory phospho-arms are uncoupled with distinct spatial outputs.

    Evidence Alanine scanning of a coiled-coil K/R cluster with functional assays; hyperosmotic-stress S315 phosphorylation with Co-IP and localization

    PMID:35409383 PMID:35955719

    Open questions at the time
    • Single lab
    • Structural basis of coiled-coil contribution to trimer stability not fully resolved
  15. 2022 Medium

    Showed CERT acts at ER–MVB contact sites with VAP-A to generate ceramide for a select RNA-containing EV population, and that HSV-1 pUL21 directly activates CERT by promoting its dephosphorylation.

    Evidence VAP-A/CERT knockdown with EV RNA/lipid profiling and imaging; SPR, SAXS structure of pUL21–CERT, mutagenesis and sphingolipid profiling

    PMID:35421371 PMID:36243114

    Open questions at the time
    • EV study from single lab
    • How pUL21 mimics or bypasses host phosphatase regulation not fully defined
  16. 2023 High

    Refined the Golgi PI4P source and uncovered a second lipid cargo, establishing the C10orf76–PI4KB distal-Golgi axis and AAG transfer for ether phospholipid synthesis.

    Evidence Genome-wide screen, super-resolution imaging, PI4KB/ACBD3/C10orf76 perturbation; in vitro AAG transfer with HPA-12, domain deletion and knockdown/rescue lipidomics

    PMID:37195633 PMID:38110110

    Open questions at the time
    • AAG transfer study single lab
    • Relative in vivo flux of ceramide versus AAG not quantified
  17. 2023 High

    Identified a dimeric helical domain mediating homeostatic autoregulation, integrating disease variants with a druggable mechanism via in vivo rescue.

    Evidence Structural characterization, patient variant analysis across 31 patients, Drosophila model with pharmacological CERT inhibition rescue

    PMID:36976648

    Open questions at the time
    • Atomic structure of the dimeric domain in full-length context not resolved
    • Translation of pharmacological rescue to mammalian disease models pending
  18. 2025 Medium

    Connected CERT-mediated ceramide transfer to phospholipase C/PIP2 signaling physiology in vivo, showing it regulates GPCR–PLC photoreceptor responses.

    Evidence Drosophila dcert loss-of-function, electrophysiology, lipidomics and genetic suppression (preprint)

    Open questions at the time
    • Preprint, not peer-reviewed
    • Whether mechanism is conserved in mammals not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CERT's two non-canonical isoform activities (GPBP kinase signaling/myofibril assembly and APP/Aβ modulation) relate mechanistically to its lipid-transfer function remains unresolved.
  • GPBP kinase activity and myofibril/GIP130 roles characterized only in single studies (idx 26, 27)
  • CERTL–APP/Aβ interaction mechanism not integrated with ceramide transfer (idx 28)
  • Membrane-assisted ceramide release mechanism remains computational (idx 25)

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0140104 molecular carrier activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005794 Golgi apparatus 4 GO:0005783 endoplasmic reticulum 3 GO:0005768 endosome 2 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-5357801 Programmed Cell Death 1
Partners
APPC10ORF76INCDPI4KBPP2CEPSILONPUL21VAPAVAPB

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 CERT catalyzes intermembrane transfer of ceramide via its START domain, with strict stereo-specificity for the natural D-erythro isomer and an acyl-chain length limit (efficient for C14–C20 but not longer chains); it does not transfer sphingosine or sphingomyelin; (1R,3R)-HPA-12 was identified as an antagonist of the CERT START domain in vitro. Cell-free lipid transfer assay, lipid binding assay, radiolabeled ceramide analogs The Journal of biological chemistry High 15596449
2006 CERT requires both its PH domain (for Golgi targeting via PI4P) and its FFAT motif (for interaction with ER-resident VAP-A and VAP-B) for efficient ER-to-Golgi ceramide transport in cells; VAP-A and VAP-B co-immunoprecipitate with CERT and this interaction is abolished by FFAT motif mutations; neither FFAT nor PH domain mutations affect ceramide transfer activity in cell-free assays, indicating these domains spatially restrict the random transfer activity of the START domain. Co-immunoprecipitation, FFAT motif mutagenesis, semi-intact cell ceramide transport assay, cell-free lipid transfer assay The Journal of biological chemistry High 16895911
2007 CERT activity is down-regulated by multiple phosphorylations at a serine-repeat motif (SRM), a substrate for casein kinase I; phosphorylation induces an autoinhibitory intramolecular interaction between the PH and START domains, inactivating both PI4P binding and ceramide transfer activities; loss of sphingomyelin and cholesterol causes dephosphorylation of CERT to activate it. In vitro phosphorylation assays, domain interaction assays, PI4P-binding assay, ceramide transfer assay, cell-based sphingomyelin depletion experiments The Journal of biological chemistry High 17442665
2008 Crystal structures of the CERT START domain in apo-form and in complex with ceramides of different acyl chain lengths reveal that one ceramide molecule is buried in a long amphiphilic cavity; hydrogen-bond networks at the far end of the cavity mediate stereo-specific ceramide recognition; cavity size dictates the acyl-chain length limit; the alpha-3 helix and Omega1 loop are proposed to act as a gate for ceramide entry. X-ray crystallography (crystal structures of apo and ceramide-bound START domain) Proceedings of the National Academy of Sciences of the United States of America High 18184806
2007 CERT is preferentially distributed to the Golgi region in cells; its PH domain specifically recognizes phosphatidylinositol 4-monophosphate (PI4P) at the Golgi for targeting; membrane contact sites between ER and Golgi are proposed as sites of efficient ceramide transfer. Subcellular fractionation, domain binding studies, fluorescence localization Biochimica et biophysica acta Medium 17314061
2007 PP2Cepsilon, an ER-resident transmembrane phosphatase, dephosphorylates CERT in a VAPA-dependent manner; PP2Cepsilon expression causes redistribution of CERT from cytoplasm to Golgi and enhances CERT-VAPA association; PP2Cepsilon knockdown attenuates CERT-VAPA interaction and sphingomyelin synthesis, identifying CERT as a physiological substrate of PP2Cepsilon. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, subcellular localization by immunofluorescence, sphingomyelin synthesis assay The Journal of biological chemistry High 18165232
2009 Crystal structures of the CERT START domain bound to HPA inhibitors reveal that the Omega1 loop adopts a different conformation compared to ceramide-bound structures, with Trp473 moving inside the cavity; surface plasmon resonance confirmed that Trp473 is important for membrane interaction, suggesting a gating mechanism for ceramide loading/unloading. X-ray crystallography, surface plasmon resonance Journal of molecular biology High 20036255
2011 Chlamydia trachomatis effector protein IncD directly binds the PH domain of CERT and recruits CERT to the inclusion membrane; this redirects ceramide trafficking toward the inclusion; CERT and VAP-A/B co-localize at ER-inclusion membrane contact sites; depletion of CERT or VAP proteins impairs bacterial development. Co-immunoprecipitation, ectopic expression, siRNA knockdown, immunofluorescence co-localization, bacterial development assay PLoS pathogens High 21731489 21909260
2012 The CERT PH domain structure determined by solution NMR reveals a characteristic basic groove near the canonical PI4P recognition site; this basic groove coordinates efficient PI4P recognition and Golgi targeting; mutations of basic groove residues cause Golgi mislocalization in living cells. Solution NMR structure determination, NMR chemical shift perturbation binding assay, cell-based localization with mutants The Journal of biological chemistry High 22869376
2014 Phosphorylation of CERT at serine 315, adjacent to the FFAT motif, markedly enhances CERT-VAP interaction and ER-to-Golgi ceramide transport activity; the phosphomimetic S315E mutant shows higher ceramide transport activity in a semi-intact cell system; S315 phosphorylation increases under sphingolipid depletion conditions and acts additively with SRM dephosphorylation to activate CERT. Semi-intact cell ceramide transport assay, co-immunoprecipitation, CERT mutant analysis, immunofluorescence, biochemical phosphorylation analysis The Journal of biological chemistry High 24569996
2014 Both the N- and C-terminal cytoplasmic regions of Chlamydia IncD are required for binding to the CERT PH domain; the IncD transmembrane region forms SDS-resistant homodimers and higher-order oligomers, which may facilitate high-affinity CERT binding. Co-transfection and co-immunoprecipitation, native gel electrophoresis, phylogenetic analysis Infection and immunity / Biochemical and biophysical research communications Medium 24595143 30314703
2018 Hyperphosphorylation-mimetic SRM substitutions (10E variant) cause an intramolecular interaction between the SRM and positively charged regions of the PH domain, directly competing with PI4P binding; this reduces PI4P-embedded membrane binding in cell-free assays and Golgi targeting in living cells. Solution NMR, PI4P-binding assay, fluorescence Golgi targeting assay in cells The Journal of biological chemistry High 29848549
2016 Targeting ceramide transport from ER to mitochondria using a mitoCERT construct (CERT with an outer mitochondrial membrane anchor) induces Bax-dependent apoptosis; apoptosis requires the ceramide transfer domain, VAP interaction via the ER, de novo ceramide synthesis, and is abolished by a bacterial ceramidase targeted to mitochondria — demonstrating that ER ceramide translocation to mitochondria directly commits cells to apoptosis. Engineered mitoCERT construct, domain deletion and FFAT mutants, CERT inhibitor HPA-12, de novo ceramide synthesis inhibition, mitochondria-targeted ceramidase, cell death assays Journal of cell science High 27888218
2008 UVB irradiation induces formation of a stable CERT homotrimer complex in keratinocytes and other cell lines; the homotrimer formation requires the middle region domain of CERT (not the PH or START domains); CERT in the homotrimer has decreased ceramide binding activity; homotrimer formation correlates with decreased sphingomyelin synthesis and increased apoptosis. Western immunoblot, mass spectrometry, ceramide binding assay, siRNA knockdown, CERT inhibitor HPA-12 The Journal of biological chemistry Medium 18411267
2019 CERT function is down-regulated by multisite SRM phosphorylation primed by protein kinase D (activated by diacylglycerol produced during ceramide-to-sphingomyelin conversion), creating a feedback mechanism; S315 phosphorylation enhances CERT-VAP binding; the PI4P pool at trans-Golgi (regulated by PI4-kinases and OSBP) controls CERT-dependent ceramide transport. Biochemical phosphorylation analysis, cell-based assays, lipid measurement (review of experimental findings) FEBS letters Medium 31254361
2018 CERT (STARD11) mediates palmitate-stimulated extracellular vesicle/exosome biogenesis in liver cells; STARD11-deficient cells release fewer extracellular vesicles, exhibit intracellular ceramide accumulation, and show reduced cellular viability; STARD11 co-localizes with ER and multivesicular bodies. STARD11 knockout cell lines, extracellular vesicle quantification, ceramide measurement, immunofluorescence co-localization The Journal of biological chemistry Medium 30139741
2020 De novo missense variants in CERT1 causing intellectual disability include gain-of-function mutations (e.g., S135P) that impair SRM hyperphosphorylation and thus prevent down-regulation of CERT activity; these mutations cause abnormal CERT activation and punctate subcellular redistribution. Whole exome sequencing, biochemical analysis of SRM phosphorylation, subcellular localization imaging PloS one Medium 33347465
2021 ID-associated CERT1 mutations S132L and G243R impair SRM hyperphosphorylation, rendering the proteins excessively active and causing punctate subcellular redistribution; a frameshift variant (dupAA) that does not impair SRM phosphorylation does not cause aberrant activity or localization, serving as a disease-matched negative control. Biochemical phosphorylation analysis, subcellular localization imaging, patient variant characterization The Journal of biological chemistry Medium 34688657
2022 A previously uncharacterized cluster of lysine/arginine residues on the outer surface of a coiled-coil region of CERT is involved in SRM phosphorylation-dependent repression of CERT function; alanine substitutions in this cluster release repression of SM synthesis, PI4P-binding, VAP binding, ceramide transfer, and Golgi localization, and partially destabilize the CERT trimer. Site-directed mutagenesis, SM synthesis assay, PI4P-binding assay, VAP co-IP, ceramide transfer assay, subcellular localization International journal of molecular sciences Medium 35955719
2022 Hyperosmotic stress induces S315 phosphorylation of CERT without altering SRM phosphorylation; under these conditions, CERT-VAP-A binding is enhanced throughout the ER (not only at ER-Golgi MCS), demonstrating that S315 phosphorylation and SRM dephosphorylation can be uncoupled and that they have distinct spatial consequences. Biochemical phosphorylation analysis, co-immunoprecipitation, immunofluorescence subcellular localization International journal of molecular sciences Medium 35409383
2022 HSV-1 pUL21, a viral phosphatase adaptor, directly interacts with CERT with submicromolar affinity; pUL21 promotes dephosphorylation of CERT, activating it and accelerating ceramide-to-sphingomyelin conversion; solution structure of the pUL21 C-terminal domain in complex with CERT PH and START domains was determined by SAXS; a single conserved pUL21 surface residue disrupts CERT binding in vitro and in cells. Click chemistry sphingolipid profiling, surface plasmon resonance, small-angle X-ray scattering (SAXS), site-directed mutagenesis, co-immunoprecipitation The Journal of biological chemistry High 36243114
2023 Several CERT1 intellectual disability variants fall in a previously uncharacterized dimeric helical domain that enables CERT homeostatic autoregulation/inactivation; disruption of this domain by de novo missense variants causes unchecked sphingolipid production; pharmacological CERT inhibition corrects morphological and motor abnormalities in a Drosophila model. Structural characterization of dimeric helical domain, patient variant analysis, Drosophila model with pharmacological rescue The Journal of clinical investigation High 36976648
2022 VAP-A and its binding partner CERT localize to multivesicular bodies (MVBs); knockdown of CERT or VAP-A reduces RNA content of small extracellular vesicles and ceramide in EVs; ceramide generated via the VAP-A/CERT axis at ER-MVB membrane contact sites drives biogenesis of a select RNA-containing EV population. siRNA knockdown, EV isolation and RNA/lipid profiling, live imaging, colocalization experiments Developmental cell Medium 35421371
2023 CERT preferentially utilizes PI4P generated by PI4KB recruited to the Golgi by C10orf76 (rather than ACBD3) for ceramide transport; super-resolution microscopy shows C10orf76 localizes predominantly at distal Golgi where sphingomyelin synthesis primarily occurs, while ACBD3 is at more proximal regions — establishing a C10orf76-PI4KB axis that orchestrates CERT-mediated ceramide delivery to distal Golgi. Genome-wide screening, PI4P measurement, super-resolution microscopy, knockdown/knockout of PI4KB, ACBD3, C10orf76 The Journal of cell biology High 37195633
2023 CERT mediates intermembrane transfer of alkylacylglycerol (AAG) in vitro; CERT inhibition (HPA-12) or START domain deletion abolishes AAG transfer; CERT suppression in HEK293 cells increases plasmanyl-PC levels (an AAG metabolite), and CERT re-introduction reduces these levels — identifying CERT as a transporter of AAG from ER to Golgi for ether phospholipid biosynthesis. In vitro lipid transfer assay, HPA-12 inhibition, domain deletion, CERT knockdown/rescue, cellular lipid measurement Archives of biochemistry and biophysics Medium 38110110
2024 Molecular dynamics simulations propose a membrane-assisted mechanism for ceramide release from the CERT START domain, in which membrane contact acts as allosteric effector and a single phosphatidylcholine lipid intercalates into the START cavity to facilitate ceramide egress; free energy calculations and experimental lipidomics confirmed CERT forms stable complexes with phosphatidylcholine in addition to ceramide. Molecular dynamics simulations, free energy calculations, experimental lipidomics The journal of physical chemistry B Low 38903016
2010 Human biliverdin reductase (hBVR) binds to GPBP (CERT1 long isoform) and down-regulates its TNF-alpha-stimulated kinase activity in HEK293A cells; hBVR siRNA knockdown modulates TNF-alpha/NF-κB-stimulated GPBP expression; the interacting domain was mapped to the C-terminal CX10C motif of hBVR. Co-immunoprecipitation, siRNA knockdown, kinase activity assay, peptide mapping The Journal of biological chemistry Medium 20177069
2011 GPBP-1 (the long isoform of CERT1) accumulates in cytoplasm of differentiating myoblasts prior to myosin synthesis; GPBP-1-deficient myoblasts show defective myofibril formation; GPBP-1 targets GIP130 (a 130-kDa interacting protein), which binds myosin and promotes its myofibrillar assembly. Loss-of-function (deficiency), overexpression, co-immunoprecipitation (GPBP-GIP130), myofibril formation assay The Journal of biological chemistry Medium 21832087
2021 CERTL (long isoform) binds to amyloid precursor protein (APP) as shown by co-immunoprecipitation; recombinant CERTL modifies Aβ aggregation and reduces Aβ neurotoxicity in neuroblastoma cells; CERTL overexpression in 5xFAD mouse brains reduces ceramide d18:1/16:0 levels, increases sphingomyelin, decreases Aβ formation, and modulates microglia toward a less pro-inflammatory phenotype. Co-immunoprecipitation, immunofluorescence, AAV-mediated overexpression in mice, mass spectrometry lipidomics, immunohistochemistry, behavior tests Alzheimer's research & therapy Medium 33597019
2018 CERT protein expression is reduced in insulin-resistance models via caspase-dependent cleavage; inhibiting CERT activity potentiates lipotoxicity-induced insulin signaling defects; CERT overexpression in vitro and in vivo decreases muscle ceramide content and improves insulin signaling; inhibition of caspase activity prevents ceramide-induced insulin signaling defects. CERT knockdown/overexpression in muscle cells, in vivo overexpression, insulin signaling assays, ceramide measurement, caspase inhibition Diabetes Medium 29759974
2017 C. psittaci recruits CERT to its inclusion; CERT knockout (CRISPR/Cas9) impairs C. psittaci infection, affecting inclusion growth and infectious progeny formation; CERT-independent sphingolipid uptake pathways exist in CERT-KO cells, and HPA-12 sensitive factors beyond CERT are involved in sphingolipid trafficking to C. psittaci. CRISPR/Cas9 CERT knockout, CERT chemical inhibition (HPA-12), fluorescent sphingolipid uptake assay, bacterial development quantification Cellular microbiology Medium 28544656
2025 In Drosophila, loss of dcert leads to elevated short-chain ceramide and reduced phosphatidylethanolamine ceramide; dcert mutants show reduced photoreceptor electrical responses to light and impaired PIP2 resynthesis following PLC activation; reducing ceramide synthesis at the ER suppresses the dcert light response phenotype — establishing that CERT-mediated ceramide transfer from ER to Golgi regulates G-protein coupled phospholipase C signaling in vivo. Loss-of-function alleles, electrophysiology (ERG), lipidomics, genetic suppressor (ceramide synthesis reduction), rescue with wild-type gene bioRxivpreprint Medium

Source papers

Stage 0 corpus · 62 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT. The Journal of biological chemistry 251 16895911
2011 The lipid transfer protein CERT interacts with the Chlamydia inclusion protein IncD and participates to ER-Chlamydia inclusion membrane contact sites. PLoS pathogens 240 21731489
2011 Chlamydia trachomatis co-opts GBF1 and CERT to acquire host sphingomyelin for distinct roles during intracellular development. PLoS pathogens 191 21909260
2004 CERT mediates intermembrane transfer of various molecular species of ceramides. The Journal of biological chemistry 189 15596449
2008 Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide. Proceedings of the National Academy of Sciences of the United States of America 176 18184806
2009 CERT-mediated trafficking of ceramide. Biochimica et biophysica acta 137 19416656
2022 VAP-A and its binding partner CERT drive biogenesis of RNA-containing extracellular vesicles at ER membrane contact sites. Developmental cell 105 35421371
2007 CERT and intracellular trafficking of ceramide. Biochimica et biophysica acta 104 17314061
2007 Interorganelle trafficking of ceramide is regulated by phosphorylation-dependent cooperativity between the PH and START domains of CERT. The Journal of biological chemistry 98 17442665
2019 Structure, functions and regulation of CERT, a lipid-transfer protein for the delivery of ceramide at the ER-Golgi membrane contact sites. FEBS letters 88 31254361
2007 Protein phosphatase 2Cepsilon is an endoplasmic reticulum integral membrane protein that dephosphorylates the ceramide transport protein CERT to enhance its association with organelle membranes. The Journal of biological chemistry 79 18165232
2014 Phosphoregulation of the ceramide transport protein CERT at serine 315 in the interaction with VAMP-associated protein (VAP) for inter-organelle trafficking of ceramide in mammalian cells. The Journal of biological chemistry 76 24569996
2014 Expression of the effector protein IncD in Chlamydia trachomatis mediates recruitment of the lipid transfer protein CERT and the endoplasmic reticulum-resident protein VAPB to the inclusion membrane. Infection and immunity 75 24595143
2008 Two sphingolipid transfer proteins, CERT and FAPP2: their roles in sphingolipid metabolism. IUBMB life 65 18459163
2016 Diverting CERT-mediated ceramide transport to mitochondria triggers Bax-dependent apoptosis. Journal of cell science 63 27888218
2016 Dead Cert: Measuring Cell Death. Cold Spring Harbor protocols 62 27934691
2009 Crystal structures of the CERT START domain with inhibitors provide insights into the mechanism of ceramide transfer. Journal of molecular biology 59 20036255
2011 CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid-specific cancer cell death through autophagy induction. The Journal of pathology 53 21953249
2018 A search for ceramide binding proteins using bifunctional lipid analogs yields CERT-related protein StarD7. Journal of lipid research 48 29343537
2013 Co-evolution of sphingomyelin and the ceramide transport protein CERT. Biochimica et biophysica acta 45 23845852
2012 Structural basis for the Golgi association by the pleckstrin homology domain of the ceramide trafficking protein (CERT). The Journal of biological chemistry 45 22869376
2018 StAR-related lipid transfer domain 11 (STARD11)-mediated ceramide transport mediates extracellular vesicle biogenesis. The Journal of biological chemistry 43 30139741
2003 The RHCE allele ceRT: D epitope 6 expression does not require D-specific amino acids. Transfusion 41 12919427
2009 Heterologous expression of the lipid transfer protein CERT increases therapeutic protein productivity of mammalian cells. Journal of biotechnology 40 19428735
2021 CERTL reduces C16 ceramide, amyloid-β levels, and inflammation in a model of Alzheimer's disease. Alzheimer's research & therapy 38 33597019
2008 Decreased ceramide transport protein (CERT) function alters sphingomyelin production following UVB irradiation. The Journal of biological chemistry 38 18411267
2017 The cellular ceramide transport protein CERT promotes Chlamydia psittaci infection and controls bacterial sphingolipid uptake. Cellular microbiology 37 28544656
2020 Liposomal FRET Assay Identifies Potent Drug-Like Inhibitors of the Ceramide Transport Protein (CERT). Chemistry (Weinheim an der Bergstrasse, Germany) 35 33047409
2007 Ceramide traffic in C6 glioma cells: evidence for CERT-dependent and independent transport from ER to the Golgi apparatus. Biochimica et biophysica acta 35 18068681
2018 Ceramide Transporter CERT Is Involved in Muscle Insulin Signaling Defects Under Lipotoxic Conditions. Diabetes 34 29759974
2023 CERT1 mutations perturb human development by disrupting sphingolipid homeostasis. The Journal of clinical investigation 26 36976648
2021 Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer. International journal of molecular sciences 26 34947980
2012 Limonoid compounds inhibit sphingomyelin biosynthesis by preventing CERT protein-dependent extraction of ceramides from the endoplasmic reticulum. The Journal of biological chemistry 26 22605339
2018 Phosphoinositide binding by the PH domain in ceramide transfer protein (CERT) is inhibited by hyperphosphorylation of an adjacent serine-repeat motif. The Journal of biological chemistry 25 29848549
2020 Intellectual disability-associated gain-of-function mutations in CERT1 that encodes the ceramide transport protein CERT. PloS one 22 33347465
2022 Herpes simplex virus 1 protein pUL21 alters ceramide metabolism by activating the interorganelle transport protein CERT. The Journal of biological chemistry 21 36243114
2013 Engineering the cellular protein secretory pathway for enhancement of recombinant tissue plasminogen activator expression in Chinese hamster ovary cells: effects of CERT and XBP1s genes. Journal of microbiology and biotechnology 21 23676904
2018 Both the N- and C- terminal regions of the Chlamydial inclusion protein D (IncD) are required for interaction with the pleckstrin homology domain of the ceramide transport protein CERT. Biochemical and biophysical research communications 20 30314703
2012 Ceramide and its transport protein (CERT) contribute to deterioration of mitochondrial structure and function in aging oocytes. Mechanisms of ageing and development 19 23246342
1994 Definition of encephalitogenic and immunodominant epitopes of guinea pig myelin basic protein (Gp-BP) in Lewis rats tolerized neonatally with Gp-BP or Gp-BP peptides. Journal of immunology (Baltimore, Md. : 1950) 19 7517426
2014 Identification of novel CERT ligands as potential ceramide trafficking inhibitors. Chembiochem : a European journal of chemical biology 16 25256104
2021 Intellectual-disability-associated mutations in the ceramide transport protein gene CERT1 lead to aberrant function and subcellular distribution. The Journal of biological chemistry 15 34688657
2015 A computational model of PKD and CERT interactions at the trans-Golgi network of mammalian cells. BMC systems biology 15 25889812
2011 Integration of non-vesicular and vesicular transport processes at the Golgi complex by the PKD-CERT network. Biochimica et biophysica acta 15 22226883
2023 The C10orf76-PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi. The Journal of cell biology 14 37195633
2010 Human biliverdin reductase suppresses Goodpasture antigen-binding protein (GPBP) kinase activity: the reductase regulates tumor necrosis factor-alpha-NF-kappaB-dependent GPBP expression. The Journal of biological chemistry 13 20177069
2015 Development of a CERT START Domain-Ceramide HTRF Binding Assay and Application to Pharmacological Studies and Screening. Journal of biomolecular screening 10 25716975
2011 Goodpasture antigen-binding protein (GPBP) directs myofibril formation: identification of intracellular downstream effector 130-kDa GPBP-interacting protein (GIP130). The Journal of biological chemistry 9 21832087
2016 Asymmetric Synthesis and Binding Study of New Long-Chain HPA-12 Analogues as Potent Ligands of the Ceramide Transfer Protein CERT. Chemistry (Weinheim an der Bergstrasse, Germany) 8 27031925
2022 Natural Ligand-Mimetic and Nonmimetic Inhibitors of the Ceramide Transport Protein CERT. International journal of molecular sciences 6 35216212
2022 Involvement of a Cluster of Basic Amino Acids in Phosphorylation-Dependent Functional Repression of the Ceramide Transport Protein CERT. International journal of molecular sciences 6 35955719
2019 N,O-Dialkyl deoxynojirimycin derivatives as CERT START domain ligands. Bioorganic & medicinal chemistry letters 6 31757669
2017 Iminosugar-based ceramide mimicry for the design of new CERT START domain ligands. Bioorganic & medicinal chemistry 6 28237558
2022 Hyperosmotic Stress Induces Phosphorylation of CERT and Enhances Its Tethering throughout the Endoplasmic Reticulum. International journal of molecular sciences 5 35409383
2024 A Membrane-Assisted Mechanism for the Release of Ceramide from the CERT START Domain. The journal of physical chemistry. B 4 38903016
2024 Live-Cell Identification of Inhibitors of the Lipid Transfer Protein CERT Using Nanoluciferase Bioluminescence Resonance Energy Transfer (NanoBRET). Angewandte Chemie (International ed. in English) 3 39450584
2020 Identification of the Interactions Interference Between the PH and START Domain of CERT by Limonoid and HPA Inhibitors. Frontiers in molecular biosciences 2 33330630
2025 Recruitment of the cellular lipid transport protein CERT to C. psittaci inclusions regulates the timing of bacterial egress. Scientific reports 1 40414946
2024 GPBP or CERT: The Roles in Autoimmunity, Cancer or Neurodegenerative Disease-A Systematic Review. International journal of molecular sciences 1 39684889
1998 The effects of the morphological response of Enterobacteriaceae to cephalosporins on PAE and CERT. Scandinavian journal of infectious diseases 1 9817524
2025 Calcaratarin D exerts neuroprotective effects in Alzheimer's disease mouse model by inhibiting CERT-mediated NF-κB pathway. Experimental neurology 0 41344499
2023 The ceramide transport protein CERT is involved in alkylacylglycerol transfer from the ER to the Golgi for the biosynthesis of ether phospholipid. Archives of biochemistry and biophysics 0 38110110

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