Affinage

MBTPS2

Membrane-bound transcription factor site-2 protease · UniProt O43462

Length
519 aa
Mass
57.4 kDa
Annotated
2026-04-28
60 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MBTPS2 (Site-2 Protease, S2P) is a polytopic membrane-embedded zinc metalloprotease that performs regulated intramembrane proteolysis of multiple transcription factor substrates—including SREBPs, ATF6, OASIS, and BBF2H7—thereby controlling cholesterol/fatty acid homeostasis, the ER unfolded protein response, and bone/cartilage development (PMID:9659902, PMID:11850408, PMID:34093655). Its HEXXH zinc-binding motif and Asp467 residue are positioned within transmembrane segments, placing the catalytic center inside the lipid bilayer to cleave substrate transmembrane helices after priming by Site-1 protease (PMID:10419520). MBTPS2 also participates in NF-κB spatial activation by cleaving SREBP1 at the Golgi within a Scap–SREBP1–IκBα supercomplex, liberating IκBα for IKK-mediated phosphorylation (PMID:37267109). Loss-of-function mutations in MBTPS2 cause a spectrum of X-linked human disorders—including IFAP syndrome, KFSD, BRESHECK syndrome, and osteogenesis imperfecta—with clinical severity correlating to the degree of residual enzymatic activity (PMID:19361614, PMID:23316014, PMID:34655156).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1997 High

    The identity of the protease responsible for Site-2 cleavage of SREBPs was unknown; complementation cloning of mutant CHO cells identified MBTPS2 as a membrane-bound zinc metalloprotease whose HEXXH motif is essential for liberating SREBP transcriptional domains, establishing S2P as a novel intramembrane protease.

    Evidence Complementation cloning in CHO cells deficient in Site-2 cleavage; HEXXH active-site mutagenesis

    PMID:9659902

    Open questions at the time
    • Exact topology and position of the active site within the membrane not yet resolved
    • Substrate range beyond SREBPs unknown
    • No structural data for S2P
  2. 1999 High

    How a metalloprotease active site could function within a hydrophobic membrane was unclear; topology mapping showed the HEIGH catalytic sequence and Asp467 reside within transmembrane segments with luminal hydrophilic loops, establishing that S2P catalyzes proteolysis inside the lipid bilayer.

    Evidence Protease protection assays, glycosylation site mapping in ER membranes, and Asp467 mutagenesis

    PMID:10419520

    Open questions at the time
    • Mechanism of water access to the intramembrane active site unresolved
    • Structural basis for substrate entry into the active site unknown
  3. 2002 High

    Whether S2P cleaved substrates beyond SREBPs was unknown; demonstration that S2P is required for ATF6 processing during ER stress expanded S2P's role from lipid homeostasis to the unfolded protein response.

    Evidence S2P-deficient CHO cell complementation; UPR reporter assays; ATF6 cleavage and nuclear translocation assays

    PMID:11850408

    Open questions at the time
    • Structural basis for dual substrate recognition (SREBP vs. ATF6) not determined
    • Other potential ER stress-related substrates not yet identified
  4. 2009 High

    The molecular basis of IFAP syndrome was unknown; identification of MBTPS2 missense mutations that impair SREBP cleavage to varying degrees, with activity levels correlating to clinical severity, established MBTPS2 as the causative gene and linked enzymatic function to disease.

    Evidence Complementation of CHO M19 cells with five patient-derived MBTPS2 mutations; SRE-reporter and cholesterol-free growth assays

    PMID:19361614

    Open questions at the time
    • Pathogenic mechanisms in affected tissues (skin, hair follicles) not directly examined
    • Relative contribution of impaired SREBP vs. ATF6 processing to clinical features unclear
  5. 2010 Medium

    Whether distinct MBTPS2 mutations cause allelic skin disorders was unclear; the p.Asn508Ser mutation was shown to reduce sterol responsiveness by approximately half, causing KFSD and extending the allelic disease spectrum.

    Evidence Functional expression in protease-deficient cells; sterol-responsive reporter assay

    PMID:20672378

    Open questions at the time
    • Whether Asn508Ser affects ATF6 or other substrate processing not tested
    • Single lab finding
  6. 2013 Medium

    The structural basis for genotype–phenotype correlations was unclear; systematic functional analysis of 11 patient variants showed that mutations clustering near the transmembrane active site cause greater enzymatic loss and more severe phenotypes, establishing a quantitative structure–function–disease relationship.

    Evidence Cell growth in lipid-free media and sterol-responsive transcription assays for 11 MBTPS2 variants from 13 families

    PMID:23316014

    Open questions at the time
    • No high-resolution structure of human S2P to map mutations precisely
    • Functional consequences for non-SREBP substrates not assessed
  7. 2016 Medium

    Structural principles governing intramembrane proteolysis by S2P-family metalloproteases—including water access and substrate entry mechanisms—were partially elucidated through crystal and cryo-EM structures of family members.

    Evidence Review of crystal/cryo-EM structures with structure-guided biochemical analyses

    PMID:26811996

    Open questions at the time
    • High-resolution structure of human MBTPS2 itself not available
    • Substrate-bound structure not determined
  8. 2021 Medium

    MBTPS2's role in bone and cartilage development was confirmed: patient fibroblasts with OI-causing mutations show stronger downregulation of SREBP targets and altered fatty acid profiles than IFAP/KFSD alleles, and MBTPS2 processes OASIS and BBF2H7 transcription factors involved in skeletal tissue formation.

    Evidence RNA-Seq transcriptome profiling and GC-MS fatty acid quantification in patient-derived fibroblasts across disease alleles

    PMID:34093655

    Open questions at the time
    • Direct cleavage of OASIS and BBF2H7 by MBTPS2 not demonstrated in this study with reconstituted assays
    • Mechanism linking altered fatty acid profiles to skeletal phenotype unclear
  9. 2021 Medium

    BRESHECK syndrome was linked to MBTPS2: a novel p.Val256Leu variant impairs both SREBP pathway activation and ER stress response, confirming that severe loss of dual pathway activity underlies the most severe MBTPS2-associated phenotype.

    Evidence Cell growth in cholesterol-depleted media; SREBP reporter assay; ER stress response assay in complementation system

    PMID:34655156

    Open questions at the time
    • Single lab; whether this variant affects OASIS/BBF2H7 processing not tested
    • In vivo validation of BRESHECK mechanisms lacking
  10. 2021 Medium

    MBTPS2 knockdown in prostate cancer cells confirmed that MBTPS2 acts through SREBP signaling to regulate cholesterol synthesis/uptake and fatty acid synthesis gene expression (FASN, ACACA), demonstrating functional relevance in cancer cell lipogenesis.

    Evidence siRNA knockdown in LNCaP cells; RNA-Seq; qPCR; Filipin III cholesterol staining

    PMID:36991255

    Open questions at the time
    • Whether MBTPS2 is essential for tumor growth in vivo not tested
    • Contribution of ATF6 branch vs. SREBP branch in cancer context not dissected
  11. 2023 Medium

    A previously unrecognized link between lipogenesis signaling and innate immunity was established: MBTPS2 cleaves SREBP1 at the Golgi within a Scap–SREBP1–IκBα supercomplex, liberating IκBα for IKK phosphorylation and NF-κB activation upon LPS stimulation.

    Evidence Co-IP identifying Scap–SREBP1–IκBα complex; S2P inhibitor and Scap/SREBP1 KO cells; LPS-stimulated NF-κB activation assays

    PMID:37267109

    Open questions at the time
    • Reciprocal validation of the supercomplex by independent methods (e.g., size-exclusion chromatography) not reported
    • In vivo relevance for innate immune responses not demonstrated
    • Whether other S2P substrates contribute to NF-κB regulation unclear
  12. 2023 Medium

    In vivo skeletal requirement for MBTPS2 was established: heterozygous Mbtps2 knock-in (N455S) and knockout mice exhibit osteochondral abnormalities, while hemizygous males show embryonic lethality, confirming essentiality for bone and cartilage homeostasis.

    Evidence Knock-in and knockout mouse models; skeletal histomorphometry; microCT; confocal imaging of lacunocanalicular network

    PMID:37797712

    Open questions at the time
    • Molecular substrates responsible for skeletal phenotype in vivo not identified
    • Whether ER stress or SREBP pathway impairment is the primary driver of skeletal defects not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the high-resolution structure of human MBTPS2, the mechanism by which it selects among multiple substrates, the relative contributions of impaired SREBP vs. ATF6 vs. OASIS/BBF2H7 processing to each clinical phenotype, and whether MBTPS2-dependent NF-κB activation is physiologically relevant in vivo.
  • No high-resolution structure of human MBTPS2
  • Substrate selectivity mechanism unknown
  • Relative pathway contributions to distinct tissue phenotypes not dissected in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 2
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-162582 Signal Transduction 1 R-HSA-168256 Immune System 1
Partners
ATF6MBTPS1NFKBIASCAPSREBF1SREBF2

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 MBTPS2 (S2P) encodes a polytopic membrane-bound zinc metalloprotease required for intramembrane proteolysis of sterol regulatory element-binding proteins (SREBPs) at Site-2, releasing their active NH2-terminal transcriptional domains from membranes. Mutation of the HEXXH putative zinc-binding residues abolishes S2P activity. Complementation cloning of mutant CHO cells deficient in Site-2 cleavage; active-site mutagenesis of HEXXH motif Molecular cell High 9659902
1999 S2P has a membrane topology in the ER where both NH2 and COOH termini face the cytosol, all three long hydrophilic loops project into the lumen, and the catalytic HEIGH sequence and Asp467 (third zinc-coordinating residue) are located within hydrophobic/transmembrane segments, positioning the active site within the membrane bilayer to cleave SREBP transmembrane helices. Protease protection assays and glycosylation site mapping in ER membranes; mutagenesis of Asp467 The Journal of biological chemistry High 10419520
2002 S2P-mediated cleavage of ER-localized ATF6 generates an N-terminal fragment required for UPR transcriptional activation; S2P deficiency in CHO cells abolishes ATF6 processing and blocks induction of UPR target genes including XBP1 mRNA upregulation, demonstrating S2P's role in the ATF6 branch of the unfolded protein response. S2P-deficient CHO cell complementation; UPR reporter gene assays; ATF6 cleavage and nuclear translocation assays Genes & development High 11850408
2009 Missense mutations in MBTPS2 cause IFAP syndrome by reducing the zinc metalloprotease activity required for SREBP cleavage and ER stress response; wild-type MBTPS2 complements protease-deficient CHO M19 cells, restoring SRE-reporter induction and cholesterol-independent growth, while five patient-derived mutations impair these functions to varying degrees correlating with clinical severity. Complementation of CHO M19 protease-deficient cells; SRE-regulated reporter gene assay; growth in cholesterol/lipid-free media; transient and stable transfection American journal of human genetics High 19361614
2010 The MBTPS2 p.Asn508Ser mutation causes KFSD by reducing MBTPS2-dependent sterol responsiveness by approximately half, as shown by in vitro functional expression studies in protease-deficient cells measuring SREBP pathway activity. In vitro functional expression in protease-deficient cells; sterol-responsive reporter assay Human mutation Medium 20672378
2013 Patient-derived MBTPS2 missense mutations cluster in transmembrane domains, and those near the active site cause greater loss of enzymatic function (as measured by cholesterol-free cell growth and sterol-responsive transcription assays) and more severe clinical phenotypes, establishing a genotype-phenotype correlation linked to catalytic activity. Cell growth assays in lipid-free media; sterol-responsive transcription assays; mutational analysis of 11 variants from 13 families Human mutation Medium 23316014
2016 Structural analysis of intramembrane proteases including S2P-family metalloproteases reveals distinct protein folds and active-site configurations, with structural data and structure-guided biochemical analyses shedding light on mechanisms of water access and substrate entry into the hydrophobic active site. Review of crystal and cryo-EM structures with structure-guided biochemical analyses Current opinion in structural biology Medium 26811996
2017 MBTPS2 directly regulates the TRPV3 gene regulatory region, and cells transfected with mutant MBTPS2 show increased cell death compared to wild-type, suggesting a regulatory axis between MBTPS2 and TRPV3 that may contribute to overlapping IFAP/Olmsted syndrome features. Luciferase reporter assays for TRPV3 promoter activity; cell viability assays with wild-type vs. mutant MBTPS2 transfection Archives of dermatological research Low 28717930
2021 MBTPS2 acts within the ATF6α/S1P/S2P signaling pathway to mediate ER stress-induced hippocampal neuronal apoptosis; pharmacological inhibition of the ATF6α pathway reduces S2P expression and downstream CHOP and caspase-12 induction along with neuronal apoptosis in a PTSD rat model. Western blotting, qRT-PCR, immunohistochemistry, TUNEL staining in SPS rat model with ATF6α pathway inhibitor AEBSF Journal of molecular neuroscience Low 33738762
2021 MBTPS2 knockdown in LNCaP prostate cancer cells impairs SREBP-dependent cholesterol synthesis and uptake and reduces expression of key fatty acid synthesis regulators FASN and ACACA, demonstrating that MBTPS2 acts through SREBP signaling to regulate lipogenesis and cholesterol metabolism in cancer cells. siRNA knockdown; RNA-Seq; qPCR pathway validation; Filipin III staining for cholesterol British journal of cancer Medium 36991255
2021 A novel MBTPS2 missense variant (p.Val256Leu) causing BRESHECK syndrome impairs cell growth in cholesterol-depleted media, attenuates SREBP pathway activation, and fails to activate the ER stress response pathway, confirming that MBTPS2 function is required for both sterol-regulated transcription and ER stress signaling. In vitro modeling: cell growth in cholesterol-depleted media; SREBP reporter assay; ER stress response assay American journal of medical genetics. Part A Medium 34655156
2021 MBTPS2 overexpression exacerbates albuminuria and promotes ER stress and renal damage in a streptozotocin-induced type 1 diabetic nephropathy mouse model, while knockdown attenuates albuminuria; chemical chaperone reduction of ER stress rescues MBTPS2-exacerbated renal damage, linking MBTPS2 function to ER stress regulation in kidney. In vivo MBTPS2 overexpression and knockdown in STZ mouse model; albuminuria measurement; ER stress markers; 4-PBA rescue experiment Archives of physiology and biochemistry Medium 32255378
2023 The lipogenesis signal cascade Scap-SREBP1-S1P/S2P orchestrates NF-κB homeostasis and spatiotemporal activation: Scap transports a Scap-SREBP1-IκBα supercomplex from the ER to the Golgi where MBTPS2 (S2P) cleaves SREBP1, liberating IκBα for IKK-mediated phosphorylation and NF-κB activation in response to LPS; inhibition of S2P diminishes LPS-induced NF-κB activation. Co-IP to identify Scap-SREBP1-IκBα complex; S2P inhibitor experiments; Scap/SREBP1 KO cells; LPS stimulation assays measuring NF-κB activation Cell reports Medium 37267109
2021 MBTPS2 is required for activating transcription factors involved in bone (OASIS) and cartilage development (BBF2H7), ER stress response (ATF6), and lipid metabolism (SREBP) via regulated intramembrane proteolysis; MBTPS2-OI patient fibroblasts show stronger downregulation of SREBP-dependent genes and altered fatty acid abundance compared to MBTPS2-IFAP/KFSD fibroblasts. RNA-sequencing transcriptome profiling of patient-derived fibroblasts; fatty acid quantification by GC-MS Frontiers in genetics Medium 34093655
2023 Heterozygous Mbtps2 knock-in (N455S) and knock-out mice show osteochondral abnormalities including thinned subchondral bone, altered osteocyte interconnectivity, and thickened articular cartilage with chondrocyte clustering; hemizygous loss-of-function leads to embryonic lethality in male mice, establishing an in vivo requirement for MBTPS2 in maintaining bone and cartilage homeostasis. Knock-in and knock-out mouse models; skeletal histomorphometry; microCT; confocal microscopy of lacunocanalicular network Bone Medium 37797712
2016 An intronic MBTPS2 variant (c.1437+4T>C) in horses causes partial skipping of exon 10, producing an aberrant MBTPS2 transcript and brindle coat phenotype, demonstrating that MBTPS2 function in skin requires correct splicing and that loss of MBTPS2 activity affects skin/hair follicle biology. Whole genome sequencing; RT-PCR transcript analysis; cosegregation analysis in a horse family G3 (Bethesda, Md.) Medium 27449517

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes & development 861 11850408
1997 Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs. Molecular cell 392 9659902
2009 IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response. American journal of human genetics 115 19361614
2021 Safety and immunogenicity of CpG 1018 and aluminium hydroxide-adjuvanted SARS-CoV-2 S-2P protein vaccine MVC-COV1901: interim results of a large-scale, double-blind, randomised, placebo-controlled phase 2 trial in Taiwan. The Lancet. Respiratory medicine 113 34655522
1999 Membrane topology of S2P, a protein required for intramembranous cleavage of sterol regulatory element-binding proteins. The Journal of biological chemistry 93 10419520
2001 Characterization of the yaeL gene product and its S2P-protease motifs in Escherichia coli. Gene 65 11750129
2010 Keratosis Follicularis Spinulosa Decalvans is caused by mutations in MBTPS2. Human mutation 51 20672378
2016 Structural biology of intramembrane proteases: mechanistic insights from rhomboid and S2P to γ-secretase. Current opinion in structural biology 39 26811996
2008 A pair of circularly permutated PDZ domains control RseP, the S2P family intramembrane protease of Escherichia coli. The Journal of biological chemistry 39 18945679
2013 Genotype-phenotype correlations emerging from the identification of missense mutations in MBTPS2. Human mutation 37 23316014
2011 MBTPS2 mutation causes BRESEK/BRESHECK syndrome. American journal of medical genetics. Part A 35 22105905
2002 Gene dosage of the spermidine/spermine N(1)-acetyltransferase ( SSAT) gene with putrescine accumulation in a patient with a Xp21.1p22.12 duplication and keratosis follicularis spinulosa decalvans (KFSD). Human genetics 35 12215835
2023 The Scap-SREBP1-S1P/S2P lipogenesis signal orchestrates the homeostasis and spatiotemporal activation of NF-κB. Cell reports 27 37267109
2021 The Escherichia coli S2P intramembrane protease RseP regulates ferric citrate uptake by cleaving the sigma factor regulator FecR. The Journal of biological chemistry 27 33865858
2020 S2P peptide-conjugated PLGA-Maleimide-PEG nanoparticles containing Imatinib for targeting drug delivery to atherosclerotic plaques. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 27 31919789
2013 Recurrent splice-site mutation in MBTPS2 underlying IFAP syndrome with Olmsted syndrome-like features in a Chinese patient. Clinical and experimental dermatology 24 24313295
2021 MBTPS2, a membrane bound protease, underlying several distinct skin and bone disorders. Journal of translational medicine 20 33743732
2011 A novel mutation in MBTPS2 causes a broad phenotypic spectrum of ichthyosis follicularis, atrichia, and photophobia syndrome in a large Chinese family. Journal of the American Academy of Dermatology 19 21315478
1995 Refinement of the localisation of the X linked keratosis follicularis spinulosa decalvans (KFSD) gene in Xp22.13-p22.2. Journal of medical genetics 17 8544196
2012 Slr0643, an S2P homologue, is essential for acid acclimation in the cyanobacterium Synechocystis sp. PCC 6803. Microbiology (Reading, England) 16 22997464
2010 A Japanese case of ichthyosis follicularis with atrichia and photophobia syndrome with an MBTPS2 mutation. Journal of human genetics 16 21179107
2017 Understanding the phenotypic similarities between IFAP and Olmsted syndrome from a molecular perspective: the interaction of MBTPS2 and TRPV3. Archives of dermatological research 14 28717930
2012 MBTPS2 mutation in a British pedigree with keratosis follicularis spinulosa decalvans. Clinical and experimental dermatology 14 22816986
2011 Intronic mutations affecting splicing of MBTPS2 cause ichthyosis follicularis, alopecia and photophobia (IFAP) syndrome. Experimental dermatology 14 21426410
2015 Ichthyosis follicularis, atrichia, and photophobia syndrome associated with a new mutation in MBTPS2. Clinical and experimental dermatology 13 25683132
2009 Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome due to mutation of the gene MBTPS2 in a large Australian kindred. Pediatric dermatology 13 19689518
2022 Evaluating the Neutralizing Ability of a CpG-Adjuvanted S-2P Subunit Vaccine Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 12 34739037
2012 IFAP syndrome with severe cutaneous, neurologic and skeletal manifestations due to a novel MBTPS2 mutation in a Polish patient. European journal of dermatology : EJD 12 22781927
2023 MBTPS2 acts as a regulator of lipogenesis and cholesterol synthesis through SREBP signalling in prostate cancer. British journal of cancer 11 36991255
2021 SARS-CoV-2 S2P spike ages through distinct states with altered immunogenicity. The Journal of biological chemistry 11 34461095
2016 Novel MBTPS2 missense mutation causes a keratosis follicularis spinulosa decalvans phenotype: mutation update and review of the literature. Clinical and experimental dermatology 11 27663151
2015 Occupancy of RNA Polymerase II Phosphorylated on Serine 5 (RNAP S5P) and RNAP S2P on Varicella-Zoster Virus Genes 9, 51, and 66 Is Independent of Transcript Abundance and Polymerase Location within the Gene. Journal of virology 11 26559844
2020 EGY3: homologue of S2P protease located in chloroplasts. Plant biology (Stuttgart, Germany) 10 31886945
2020 Involvement of a Membrane-Bound Amphiphilic Helix in Substrate Discrimination and Binding by an Escherichia coli S2P Peptidase RseP. Frontiers in microbiology 10 33329500
2016 Biochemical Characterization of Function and Structure of RseP, an Escherichia coli S2P Protease. Methods in enzymology 10 28065260
1997 High-resolution mapping by YAC fragmentation of a 2.5-Mb Xp22 region containing the human RS, KFSD and CLS disease genes. Mammalian genome : official journal of the International Mammalian Genome Society 9 9195994
2023 Mice heterozygous for an osteogenesis imperfecta-linked MBTPS2 variant display a compromised subchondral osteocyte lacunocanalicular network associated with abnormal articular cartilage. Bone 8 37797712
2021 Molecular Mechanism of the ATF6α/S1P/S2P Signaling Pathway in Hippocampal Neuronal Apoptosis in SPS Rats. Journal of molecular neuroscience : MN 8 33738762
2016 An Intronic MBTPS2 Variant Results in a Splicing Defect in Horses with Brindle Coat Texture. G3 (Bethesda, Md.) 8 27449517
2020 RNA polymerase II CTD S2P is dispensable for embryogenesis but mediates exit from developmental diapause in C. elegans. Science advances 7 33298437
2019 A novel mutation in MBTPS2 causes ichthyosis follicularis, alopecia, and photophobia syndrome. Molecular genetics & genomic medicine 7 31215178
2016 Involvement of TLR6 in the induction of COX-2, PGE2 and IL-10 in macrophages by lipids from virulent S2P and attenuated R1A Babesia bovis strains. Veterinary parasitology 7 27198789
2023 S2P intramembrane protease RseP degrades small membrane proteins and suppresses the cytotoxicity of intrinsic toxin HokB. mBio 5 37409810
2023 Phase I study of a non-S2P SARS-CoV-2 mRNA vaccine LVRNA009 in Chinese adults. Vaccine 5 37925316
2021 A novel MBTPS2 variant associated with BRESHECK syndrome impairs sterol-regulated transcription and the endoplasmic reticulum stress response. American journal of medical genetics. Part A 5 34655156
2020 MBTPS2 exacerbates albuminuria in streptozotocin-induced type I diabetic nephropathy by promoting endoplasmic reticulum stress-mediated renal damage. Archives of physiology and biochemistry 5 32255378
2013 Babesia bovis: lipids from virulent S2P and attenuated R1A strains trigger differential signalling and inflammatory responses in bovine macrophages. Parasitology 5 23286221
2013 Novel MBTPS2 missense mutation in the N-terminus transmembrane domain in a patient with ichthyosis follicularis, alopecia, and photophobia syndrome. Pediatric dermatology 5 23551428
2023 Perturbations in fatty acid metabolism and collagen production infer pathogenicity of a novel MBTPS2 variant in Osteogenesis imperfecta. Frontiers in endocrinology 4 37305034
2022 Hamsters Protected from SARS-CoV-2 Delta Variant Challenge after Two Doses of Adjuvanted SARS-CoV-2 Recombinant Spike Protein (S-2P) and One Dose of Beta S-2P. The Journal of infectious diseases 4 35451470
2021 Omics Profiling of S2P Mutant Fibroblasts as a Mean to Unravel the Pathomechanism and Molecular Signatures of X-Linked MBTPS2 Osteogenesis Imperfecta. Frontiers in genetics 4 34093655
2017 S2P: A software tool to quickly carry out reproducible biomedical research projects involving 2D-gel and MALDI-TOF MS protein data. Computer methods and programs in biomedicine 4 29512488
2023 Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates. bioRxiv : the preprint server for biology 3 38076895
2022 The role of p53 in the DNA damage-related ubiquitylation of S2P RNAPII. PloS one 3 35511765
2022 Intranasal nanoemulsion adjuvanted S-2P vaccine demonstrates protection in hamsters and induces systemic, cell-mediated and mucosal immunity in mice. PloS one 3 36322572
2022 An intronic splice-site variant in MBTPS2 underlies ichthyosis follicularis with atrichia and photophobia syndrome. The Journal of dermatology 2 36539961
2023 A Brazilian case of IFAP syndrome with severe congenital ichthyosis and limb malformations caused by a rare variant in MBTPS2. Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo 1 37042943
2022 A Novel Mutation in the MBTPS2 Gene Resulting in Ichthyosis Follicularis, Atrichia, and Photophobia Syndrome. Annals of dermatology 1 35221597
2026 Intranasal S-2P and lentinan formulation confers broad protection against SARS-CoV-2 VOCs via IFN-γ-dominant mechanisms. NPJ vaccines 0 41611712
2026 Long-read RNA sequencing reveals extensive transcript isoform changes in a patient with IFAP syndrome with a recurrent intronic MBTPS2 variant. Human genome variation 0 41980932