Affinage

CBS

Cystathionine beta-synthase · UniProt P35520

Length
551 aa
Mass
60.6 kDa
Annotated
2026-06-09
100 papers in source corpus 25 papers cited in narrative 26 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

CBS (cystathionine β-synthase) is a PLP-dependent enzyme that catalyzes the condensation of serine and homocysteine to cystathionine and concomitantly generates hydrogen sulfide (H2S), positioning it as the entry point of the transsulfuration pathway and a major source of signaling sulfide (PMID:22240119). Enzyme output is set by allosteric control through the C-terminal regulatory (Bateman/CBS) domain, which binds adenosine derivatives including AMP, ATP, and S-adenosylmethionine; SAM occupies two classes of sites — high-affinity sites that kinetically stabilize the protein and modulate its steady-state level, and low-affinity sites that drive catalytic activation (PMID:14722619, PMID:22985361, PMID:24667534). Homocystinuria-causing missense mutations act by distinct routes: catalytic-core substitutions reduce activity or expression (and one, G307S, restricts the conformational flexibility needed to form the catalytic intermediate), whereas C-terminal mutations trap abnormal oligomers that cannot reach the SAM-activated state, defects partially correctable by chemical chaperones (PMID:20308073, PMID:30030379, PMID:23974653). Beyond intrinsic regulation, CBS is post-translationally controlled by cGMP/PKG-dependent phosphorylation at Ser227 and by physical interaction with the circadian repressor CRY1, which reciprocally modulates CBS activity while CBS augments CRY1-mediated repression of CLOCK/BMAL1 (PMID:32383312, PMID:27509878). CBS is a transcriptional target of multiple stress and inflammatory programs — NRF2, ATF3, ATF6, and NF-κB — that converge to raise CBS-derived H2S (PMID:31819185, PMID:26229403, PMID:38007457, PMID:38490069). Downstream, this H2S acts through protein S-sulfhydration of targets including HuR (destabilizing COX-2 mRNA), phosphodiesterases PDE4A/PDE8A (elevating cAMP/PKA signaling for steroidogenesis), and SIRT1 (limiting hepatic lipogenesis), and it tonically suppresses mitochondrial Complex IV from a mitochondrial pool of the enzyme (PMID:36725190, PMID:33713531, PMID:38007457, PMID:31481613). Functionally, CBS-driven sulfide supports cancer cell bioenergetics and ferroptosis resistance, modulates erythropoiesis and the heme pathway, and contributes to cytoprotection and angiogenesis across tissues (PMID:31819185, PMID:24236104, PMID:38490069, PMID:31551410).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2001 Medium

    Established a genetic determinant of CBS activity by linking a regulatory-region VNTR to reduced enzyme function, connecting sequence variation to the transsulfuration phenotype.

    Evidence CBS enzyme activity in patient fibroblasts, RT-PCR splicing analysis, and VNTR genotyping

    PMID:11528503

    Open questions at the time
    • Mechanism linking repeat number to splicing outcome not fully resolved
    • Effect size on clinical phenotype unclear
  2. 2003 Medium

    Defined the tissue and subcellular distribution of CBS, showing predominantly cytosolic neuronal expression with developmental regulation, framing where the enzyme acts.

    Evidence In situ hybridization, Northern blot, and immunohistochemistry in mouse brain and embryonic tissues

    PMID:12588964

    Open questions at the time
    • No functional consequence linked to localization
    • Mitochondrial pool not yet identified
  3. 2004 High

    Identified the CBS domains as adenosine-derivative sensing modules, explaining how nucleotide ligands and disease mutations converge on the enzyme's regulatory region.

    Evidence In vitro binding assays with purified CBS-domain proteins and disease-mutant functional tests

    PMID:14722619

    Open questions at the time
    • Quantitative coupling of ligand binding to catalytic rate not defined
    • Structural basis of mutant binding loss not resolved here
  4. 2013 High

    Resolved the dual logic of SAM regulation — distinguishing high-affinity stabilizing sites that set protein level from low-affinity activating sites — explaining how a single metabolite both stabilizes and activates CBS.

    Evidence ITC, functional enzyme assays, and kinetic modeling on purified WT and homocystinuria-mutant CBS

    PMID:22985361 PMID:23974653

    Open questions at the time
    • Structural geometry of the six sites not directly visualized
    • In vivo contribution of stabilization vs activation hard to disentangle
  5. 2012 High

    Dissected the conserved catalytic core through a divergent ortholog lacking heme and the Bateman domain, isolating the PLP-dependent module responsible for cystathionine/H2S production and homocysteine homeostasis.

    Evidence Truncation/active-site mutagenesis of C. elegans CBS-1, PLP-binding assays, and RNAi knockdown with homocysteine measurement

    PMID:22240119

    Open questions at the time
    • Ortholog lacks the regulatory features of human CBS
    • Heme contribution to catalysis not addressed
  6. 2010 High

    Classified homocystinuria mutations mechanistically and showed chemical chaperones can rescue folding-defective mutants, separating conformational defects from irreversibly inactivated states.

    Evidence Purified CBS mutants expressed with chemical chaperones, activity, thermal stability, and SAM-stimulation assays

    PMID:20308073

    Open questions at the time
    • In vivo chaperone efficacy not tested here
    • R125Q/E176K activation failure structurally unexplained
  7. 2018 High

    Pinpointed a single-residue catalytic mechanism by which G307S abolishes activity without destabilizing the protein, isolating conformational flexibility at the active site as essential for intermediate formation.

    Evidence Transgenic G307S mouse, enzyme assays, proteasome inhibition, and molecular dynamics simulation

    PMID:30030379

    Open questions at the time
    • Simulation prediction not confirmed by crystallography
    • Generalizability to other core mutations untested
  8. 2011 Medium

    Linked extracellular signals to CBS-dependent cytoprotection, showing monoamine/mTOR-driven CBS expression generates H2S that limits oxidative apoptosis.

    Evidence CBS mRNA/protein measurement, siRNA and pharmacological inhibition, ROS and caspase assays in smooth muscle cells

    PMID:21829469

    Open questions at the time
    • Direct mTOR-to-CBS transcriptional link not mapped
    • H2S effector targets not identified
  9. 2014 Medium

    Connected CBS-derived H2S to cancer bioenergetics, demonstrating that SAM-activated CBS fuels tumor proliferation, mitochondrial respiration, and chemoresistance.

    Evidence Recombinant enzyme assays, CBS silencing in vitro/in vivo, bioenergetic flux measurements, and orthotopic tumor model

    PMID:24236104 PMID:24667534

    Open questions at the time
    • Biphasic SAM effect mechanism (CBS-independent at high dose) unresolved
    • Direct sulfhydration targets in this context not identified
  10. 2016 Medium

    Identified Ser227 phosphorylation via cGMP/PKG as a post-translational activation switch for CBS, coupling receptor signaling to H2S output and tissue relaxation.

    Evidence Site-specific phosphorylation analysis, CBS inhibition, and functional bladder strip and T24 cell assays

    PMID:27509878

    Open questions at the time
    • Direct kinase-substrate biochemistry on Ser227 not reconstituted
    • Effect on enzyme kinetics not quantified
  11. 2019 High

    Established a mitochondrial CBS pool whose H2S tonically suppresses Complex IV, linking CBS overdosage to the mitochondrial and cognitive phenotypes of Down syndrome.

    Evidence Subcellular fractionation, CBS inhibition/siRNA with Complex IV and respiration assays in DS fibroblasts; Cbs KO/OE mice with behavioral and proteomic analysis

    PMID:30649339 PMID:31481613

    Open questions at the time
    • Import mechanism targeting CBS to mitochondria undefined
    • Molecular targets of mitochondrial H2S beyond Complex IV not enumerated
  12. 2019 Medium

    Extended CBS regulation to NRF2-driven transcription and broadened its physiological reach to ferroptosis resistance and erythropoiesis/heme homeostasis.

    Evidence CBS/NRF2 RNAi and overexpression with ferroptosis/ROS readouts; CBS KO mouse heme-pathway and iron analysis

    PMID:31551410 PMID:31819185

    Open questions at the time
    • Direct NRF2 binding at CBS promoter not shown in this entry
    • Mechanism linking CBS to ALAS2/FECH regulation unresolved
  13. 2020 High

    Revealed bidirectional coupling between CBS and the circadian clock through physical interaction with CRY1, integrating sulfur metabolism with circadian timekeeping.

    Evidence Co-IP, circadian period assays, CBS activity rescue in Cry1-/- liver, and transgenic mouse metabolomics

    PMID:32383312

    Open questions at the time
    • Interaction interface and stoichiometry not mapped
    • Whether CRY1 binding alters CBS oligomerization unknown
  14. 2021 High

    Identified protein S-sulfhydration as the effector mechanism of CBS-derived H2S, with HuR and phosphodiesterases as direct targets controlling mRNA stability and cAMP/PKA-driven steroidogenesis.

    Evidence Biotin switch sulfhydration assays, CBS CRISPR KO and KO mouse models, mRNA chase, and PKA pathway analysis

    PMID:33713531 PMID:36725190

    Open questions at the time
    • Sulfhydrated cysteine residues on targets not all mapped
    • Selectivity of CBS-derived vs other sulfide sources unclear
  15. 2021 Medium

    Linked CBS loss to genome-wide epigenetic remodeling resembling gastric cancer methylation patterns, expanding CBS function from metabolism to DNA methylation and inflammation control.

    Evidence CRISPR CBS deletion in gastric epithelial cells, global methylation profiling, NF-κB activity and H2S assays, proteomics

    PMID:34074348

    Open questions at the time
    • Causal link from H2S to specific methylation changes not established
    • Whether NF-κB is cause or consequence unresolved
  16. 2023 Medium

    Demonstrated ATF6 as a direct transcriptional driver of CBS via promoter binding, channeling ER-stress signaling into H2S-mediated SIRT1 sulfhydration and metabolic control in liver.

    Evidence ATF6 liver KO mice, ChIP at CBS promoter, H2S and SIRT1 sulfhydration assays in high-fat diet model

    PMID:38007457

    Open questions at the time
    • SIRT1 sulfhydration site not defined
    • Quantitative contribution to lipid phenotype unclear
  17. 2024 Medium

    Defined an ATF3-CBS axis sustaining ferroptosis resistance through TCA-cycle support under cystine deprivation, reinforcing CBS as a stress-adaptive transcriptional target in cancer.

    Evidence ATF3/CBS gain- and loss-of-function, ferroptosis and TCA metabolic assays, CRC patient correlation

    PMID:38490069

    Open questions at the time
    • Direct ATF3 binding at CBS promoter not shown
    • Metabolic node connecting CBS to TCA flux not pinpointed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse transcriptional inputs (NRF2, ATF3, ATF6, NF-κB), post-translational switches (Ser227 phosphorylation, CRY1 binding), and subcellular partitioning are integrated to set CBS-derived H2S output and target selection in a given cell remains unresolved.
  • No unified model coupling transcriptional, allosteric, and PTM regulation
  • Determinants of mitochondrial vs cytosolic CBS targeting unknown
  • Rules governing which proteins are S-sulfhydrated not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0016829 lyase activity 2 GO:0098772 molecular function regulator activity 1 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005739 mitochondrion 2 GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-9909396 Circadian clock 1
Partners
CRY1HURPDE4APDE8ASIRT1

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Tandem pairs of CBS domains from cystathionine beta-synthase bind AMP, ATP, or S-adenosyl methionine; disease-causing mutations in the CBS domains impair this nucleotide binding, establishing CBS domains as adenosine-derivative sensing modules. In vitro binding assays with purified CBS domain proteins; functional assessment of disease mutants The Journal of clinical investigation High 14722619
2013 Human CBS contains two classes of SAM-binding sites in the C-terminal regulatory domain: a high-affinity set of two sites involved in kinetic stabilization, and a low-affinity set of four sites responsible for enzyme activation. SAM-induced stabilization modulates steady-state CBS levels in vivo. Calorimetric methods (ITC), functional enzyme assays, kinetic modeling on purified WT and homocystinuria mutant CBS proteins The Biochemical journal High 22985361
2010 Eight homocystinuria-causing CBS missense mutants (P49L, P78R, A114V, R125Q, E176K, P422L, I435T, S466L) can be rescued by chemical chaperones during expression, yielding tetrameric enzymes with restored catalytic activity; R125Q and E176K fail to respond to SAM stimulation or thermal activation, indicating their conformations cannot reach the activated state. Purification of CBS mutant proteins expressed in E. coli with chemical chaperones; enzyme activity assays; thermal stability measurements; SAM stimulation assays The Journal of biological chemistry High 20308073
2012 CBS catalyzes PLP-dependent reactions to produce cystathionine and H2S; the C. elegans CBS-1 ortholog has a unique tandem-repeat architecture with one active PLP-binding catalytic module and one inactive N-terminal module, lacks heme and the regulatory Bateman domain, forms monomers, and its knockdown causes ~10-fold elevation of homocysteine. Truncation and active-site mutagenesis of purified CBS-1; PLP-binding assays; in vivo RNAi knockdown; homocysteine measurement The Biochemical journal High 22240119
2018 The p.G307S CBS mutation abolishes enzyme activity without affecting protein stability or multimerization; molecular dynamics simulation indicates the substitution restricts Y308 conformational flexibility required for formation of the pyridoxal-cystathionine catalytic intermediate. Transgenic mouse model expressing p.G307S CBS; enzyme activity assays; proteasome inhibitor treatment; molecular dynamics simulation The Journal of biological chemistry High 30030379
2013 Reduced SAM activation of CBS is caused by C-terminal domain mutations that produce abnormal oligomeric conformations unable to reach the activated state, while catalytic-core mutations reduce protein expression and activity; SAM-activation defect confirmed in both patient fibroblasts and recombinant mutant proteins. Retrospective fibroblast activity assays; heterologous CBS mutant expression in E. coli; Western blotting; enzyme activity in absence/presence of SAM and PLP Journal of inherited metabolic disease Medium 23974653
2019 CBS-derived H2S directly suppresses mitochondrial Complex IV activity; pharmacological inhibition of CBS (aminooxyacetate) or siRNA silencing in Down syndrome fibroblasts normalizes H2S levels, restores Complex IV activity, improves mitochondrial electron transport and ATP synthesis, and restores cell proliferation. CBS inhibition (aminooxyacetate) and siRNA knockdown in DS fibroblasts; measurement of H2S, polysulfides, mitochondrial oxygen consumption, ATP generation, Complex IV activity Proceedings of the National Academy of Sciences of the United States of America High 31481613
2019 Cbs overdosage is necessary and sufficient for recognition-memory deficits in Down syndrome mouse models; Cbs interacts genetically (epistasis) with Dyrk1a to control memory, and proteomic analysis implicates synaptic transmission, cell projection morphogenesis, and actin cytoskeleton pathways. Genetic deletion and transgenic overexpression of Cbs in mice; novel object recognition behavioral testing; pharmacological rescue; genetic epistasis with Dyrk1a; proteomic analysis Human molecular genetics High 30649339
2020 CBS physically interacts with the core circadian protein CRY1; in cells, CBS augments CRY1-mediated repression of the CLOCK/BMAL1 complex and shortens circadian period; CRY1 binding reciprocally modulates CBS enzymatic activity; liver extracts from Cry1-/- mice show reduced CBS activity restored by exogenous WT CRY1. Co-immunoprecipitation; circadian period assays; CBS enzymatic activity in Cry1-/- liver extracts with/without exogenous CRY1; metabolomics; transgenic CbsZn/Zn mouse circadian analysis The FEBS journal High 32383312
2016 Muscarinic receptor (M1/M3) activation in human urothelium phosphorylates CBS at Ser227 via the cGMP/PKG pathway, stimulating H2S production and cGMP, which promotes bladder relaxation; CBS (but not CSE) inhibition mimics urothelium removal and increases carbachol-induced contraction. CBS inhibition pharmacology; site-specific phosphorylation analysis (Ser227); functional bladder strip assays; T24 cell line experiments; receptor blockade Scientific reports Medium 27509878
2019 CBS-derived H2S production is activated by NRF2 transcriptional upregulation of CBS in erastin-resistant ovarian cancer cells; CBS knockdown causes ferroptotic cell death in resistant cells, while CBS overexpression confers resistance, demonstrating NRF2/CBS signaling as a ferroptosis resistance mechanism through the transsulfuration pathway. RNAi knockdown of CBS and NRF2; CBS overexpression; cell viability and ROS measurement; metabolite analysis of transsulfuration pathway British journal of cancer Medium 31819185
2014 CBS regulates mitochondrial bioenergetics in ovarian cancer cells by controlling ROS production, oxygen consumption, and ATP generation; CBS silencing via nanoliposomal siRNA inhibits tumor growth and sensitizes cisplatin-resistant cells. CBS siRNA silencing (in vitro and in vivo); mitochondrial ROS, oxygen consumption, ATP measurements; orthotopic mouse model PloS one Medium 24236104
2014 SAM, as an allosteric CBS activator, markedly enhances CBS-mediated H2S production in vitro; low-to-intermediate SAM concentrations stimulate HCT116 colon cancer cell proliferation and bioenergetics in a CBS-dependent manner (attenuated by AOAA or CBS silencing), while high SAM concentrations inhibit proliferation by CBS-independent mechanisms. Recombinant CBS enzyme assay; HCT116 cell proliferation (xCELLigence); extracellular flux bioenergetics; CBS stable silencing; AOAA pharmacological inhibition Nitric oxide : biology and chemistry Medium 24667534
2015 TLR4 activation upregulates CBS expression in dorsal root ganglion neurons via NF-κB signaling; NF-κB inhibition reduces CBS upregulation and attenuates visceral hypersensitivity in a rat IBS model. Western blot; intrathecal pharmacological inhibition of TLR4 and NF-κB; LPS stimulation of cultured DRG neurons; patch-clamp electrophysiology World journal of gastroenterology Medium 26229403
2011 Serotonin and dopamine increase CBS expression via mTOR signaling and stimulate H2S production in rat smooth muscle cells, protecting against hypothermia/rewarming-induced ROS and apoptosis; CBS inhibition (pharmacological or siRNA) abolishes these protective effects. CBS mRNA/protein measurement; siRNA knockdown; pharmacological CBS inhibition; ROS measurement; caspase activity assay; organ preservation experiments PloS one Medium 21829469
2020 Estradiol-17β (E2) specifically stimulates CBS (but not CSE) expression and H2S production in endometrial stromal cells via estrogen receptor (blocked by ICI 182780); stromal CBS-derived H2S promotes endometrial microvascular endothelial cell angiogenesis in a paracrine manner. CBS/CSE expression analysis; ICI 182780 receptor blockade; CBS pharmacological inhibition; co-culture migration assay; in vivo endometrial analysis across hormonal states Endocrinology Medium 32987401
2021 H2S produced by CBS promotes S-sulfhydration of HuR (human antigen R), which decreases HuR binding to COX-2 mRNA, reducing COX-2 mRNA stability and expression; CBS heterozygous knockout mice show decreased HuR sulfhydration and increased COX-2 in colon. Biotin switch technique for S-sulfhydration; CRISPR/Cas9 CBS knockout; ActD chase assay for mRNA stability; CBS+/- mouse colitis model; immunofluorescence Journal of advanced research High 36725190
2021 CBS-derived H2S promotes testosterone synthesis in MLTC-1 cells by sulfhydrylating PDE4A and PDE8A (reducing their activity), thereby elevating cAMP and activating PKA pathway; CBS overexpression increases StAR, P450scc, P450c17 and 3β-HSD expression. CBS overexpression/knockdown; CBS/H2S measurement; biotin switch technique for PDE sulfhydrylation; PKA pathway analysis; RT-qPCR and western blot Journal of cellular and molecular medicine Medium 33713531
2021 CBS knockout using CRISPR in normal gastric epithelial cells induces widespread DNA methylation changes overlapping with gastric cancer CIMP patterns, and CBS loss reduces H2S and increases NF-κB activity, linking CBS to both epigenetic regulation and inflammation. CRISPR deletion of CBS; global DNA methylation profiling; NF-κB activity assay; H2S measurement; proteomics; comparison with primary gastric cancer CIMP patterns Genome biology Medium 34074348
2023 ATF6 directly binds the CBS gene promoter and transcriptionally upregulates CBS expression; ATF6-driven CBS activity increases H2S synthesis, which sulfhydrates SIRT1, reducing lipogenesis and inflammation in fatty liver. ATF6 liver-specific knockout mice; chromatin immunoprecipitation (ChIP) at CBS promoter; H2S measurement; SIRT1 sulfhydration assay; high-fat diet model European journal of medical research Medium 38007457
2024 ATF3 positively regulates CBS expression under cystine deprivation, conferring ferroptosis resistance in colorectal cancer; CBS suppression sensitizes cells to ferroptosis by targeting the mitochondrial TCA cycle; ATF3-CBS axis positively correlates with CRC progression. ATF3 and CBS gain/loss-of-function; ferroptosis assays; metabolic (TCA cycle) analysis; CRC patient correlation Redox biology Medium 38490069
2019 CBS deficiency suppresses erythropoiesis by reducing expression of heme biosynthetic enzymes ALAS2 and FECH, heme exporter FLVCR, HIF-2α, EPO, and EPOR in CBS knockout mice, while increasing IL-6, hepcidin, and iron content. CBS-/-, CBS+/-, and CBS+/+ mouse comparison; Western blot and qPCR for heme pathway proteins; blood and bone marrow iron content measurement Cell death & disease Medium 31551410
2003 CBS protein is localized predominantly in the cytosol of neurons, with strongest expression in Purkinje cell bodies/neuronal processes and Ammon's horn neurons in adult mouse brain; CBS expression peaks during cerebellar development and is present in liver from early embryonic stages. In situ hybridization; Northern blotting; immunohistochemistry in mouse brain and developmental tissues The journal of histochemistry and cytochemistry Medium 12588964
2019 CBS localizes to both cytosol and mitochondria in Down syndrome fibroblasts, and mitochondrial CBS-derived H2S is responsible for tonic suppression of Complex IV. CBS subcellular fractionation and localization in DS fibroblasts; CBS inhibition/siRNA with Complex IV activity measurement Proceedings of the National Academy of Sciences of the United States of America Medium 31481613
2001 A 31 bp VNTR spanning the exon 13-intron 13 boundary of the CBS gene is associated with reduced CBS enzyme activity in patient fibroblasts (measured directly) and elevated post-methionine load homocysteine; RT-PCR shows evidence of alternative splicing at this junction dependent on repeat number. CBS enzyme activity in cultured fibroblasts; RT-PCR; VNTR genotyping in patients and controls European journal of human genetics Medium 11528503
2012 CBS (alongside CSE) is expressed in adrenocortical cells and is required for H2S generation; CBS/CSE inhibition or siRNA knockdown causes mitochondrial oxidative stress and dysfunction and blunts corticosterone responses to ACTH; LPS inhibits CBS/CSE expression and H2S production in adrenal glands. CBS/CSE inhibitors and siRNA in adrenocortical cells; in vivo adrenal suppression model; mitochondrial function assays; corticosterone measurement Antioxidants & redox signaling Medium 24702258

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88. Nature biotechnology 801 17259976
2004 CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. The Journal of clinical investigation 605 14722619
2021 Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. Journal of advanced research 222 35499052
2005 CBS domains: structure, function, and pathology in human proteins. American journal of physiology. Cell physiology 209 16275737
2013 Cystathionine beta-synthase (CBS) contributes to advanced ovarian cancer progression and drug resistance. PloS one 205 24236104
2019 Activation of the reverse transsulfuration pathway through NRF2/CBS confers erastin-induced ferroptosis resistance. British journal of cancer 182 31819185
2011 The CBS domain: a protein module with an emerging prominent role in regulation. ACS chemical biology 138 21958115
2019 Overproduction of H2S, generated by CBS, inhibits mitochondrial Complex IV and suppresses oxidative phosphorylation in Down syndrome. Proceedings of the National Academy of Sciences of the United States of America 121 31481613
2021 Exosomal lncRNA-H19 promotes osteogenesis and angiogenesis through mediating Angpt1/Tie2-NO signaling in CBS-heterozygous mice. Theranostics 117 34335960
2003 Expression of the cystathionine beta synthase (CBS) gene during mouse development and immunolocalization in adult brain. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 116 12588964
1988 The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17. American journal of human genetics 116 2894761
2013 CBS domains: Ligand binding sites and conformational variability. Archives of biochemistry and biophysics 114 24161944
2011 Hydrogen sulfide generation in mammals: the molecular biology of cystathionine-β- synthase (CBS) and cystathionine-γ-lyase (CSE). Inflammation & allergy drug targets 106 21275900
2006 A novel deletion in progranulin gene is associated with FTDP-17 and CBS. Neurobiology of aging 104 17157414
2012 Increased endogenous H2S generation by CBS, CSE, and 3MST gene therapy improves ex vivo renovascular relaxation in hyperhomocysteinemia. American journal of physiology. Cell physiology 102 22517358
1998 The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms. Genomics 97 9790750
2007 Polymorphism and regulation of the spxB (pyruvate oxidase) virulence factor gene by a CBS-HotDog domain protein (SpxR) in serotype 2 Streptococcus pneumoniae. Molecular microbiology 94 18179423
2014 Effect of S-adenosyl-L-methionine (SAM), an allosteric activator of cystathionine-β-synthase (CBS) on colorectal cancer cell proliferation and bioenergetics in vitro. Nitric oxide : biology and chemistry 92 24667534
2012 Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBS. Parkinsonism & related disorders 82 22818528
2015 Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats. Nitric oxide : biology and chemistry 75 25617698
2013 Human cystathionine β-synthase (CBS) contains two classes of binding sites for S-adenosylmethionine (SAM): complex regulation of CBS activity and stability by SAM. The Biochemical journal 75 22985361
2022 Apolipoprotein C1 promotes glioblastoma tumorigenesis by reducing KEAP1/NRF2 and CBS-regulated ferroptosis. Acta pharmacologica Sinica 65 35581292
2011 FUS and TDP43 genetic variability in FTD and CBS. Neurobiology of aging 65 21943958
2013 L-Cysteine promotes the proliferation and differentiation of neural stem cells via the CBS/H₂S pathway. Neuroscience 63 23376738
2010 Rescue of cystathionine beta-synthase (CBS) mutants with chemical chaperones: purification and characterization of eight CBS mutant enzymes. The Journal of biological chemistry 62 20308073
2012 Overexpression of rice CBS domain containing protein improves salinity, oxidative, and heavy metal tolerance in transgenic tobacco. Molecular biotechnology 61 22302312
2022 CLNN-loop: a deep learning model to predict CTCF-mediated chromatin loops in the different cell lines and CTCF-binding sites (CBS) pair types. Bioinformatics (Oxford, England) 59 35997565
2012 Polymorphisms in MTHFR, MS and CBS genes and homocysteine levels in a Pakistani population. PloS one 56 22470444
2011 Serotonin and dopamine protect from hypothermia/rewarming damage through the CBS/H2S pathway. PloS one 47 21829469
2000 Polymorphisms in the CBS gene associated with decreased risk of coronary artery disease and increased responsiveness to total homocysteine lowering by folic acid. Molecular genetics and metabolism 46 10833331
2019 Cbs overdosage is necessary and sufficient to induce cognitive phenotypes in mouse models of Down syndrome and interacts genetically with Dyrk1a. Human molecular genetics 43 30649339
2014 CBS and CSE are critical for maintenance of mitochondrial function and glucocorticoid production in adrenal cortex. Antioxidants & redox signaling 42 24702258
2001 A 31 bp VNTR in the cystathionine beta-synthase (CBS) gene is associated with reduced CBS activity and elevated post-load homocysteine levels. European journal of human genetics : EJHG 41 11528503
2016 Urothelium muscarinic activation phosphorylates CBS(Ser227) via cGMP/PKG pathway causing human bladder relaxation through H2S production. Scientific reports 40 27509878
1998 Molecular cloning, sequencing, and heterologous expression of the vaoA gene from Penicillium simplicissimum CBS 170.90 encoding vanillyl-alcohol oxidase. The Journal of biological chemistry 40 9525880
2015 Prolyl isomerase Pin1 negatively regulates AMP-activated protein kinase (AMPK) by associating with the CBS domain in the γ subunit. The Journal of biological chemistry 38 26276391
2006 A common mutation in the CBS gene explains a high incidence of homocystinuria in the Qatari population. Human mutation 38 16786517
1998 Purification, characterisation, and gene cloning of transglutaminase from Streptoverticillium cinnamoneum CBS 683.68. Biochimie 37 9672751
2021 The CBS-H2S axis promotes liver metastasis of colon cancer by upregulating VEGF through AP-1 activation. British journal of cancer 35 34952931
2018 MiR-125b-5p is involved in oxygen and glucose deprivation injury in PC-12 cells via CBS/H2S pathway. Nitric oxide : biology and chemistry 34 29777774
2020 CRY1-CBS binding regulates circadian clock function and metabolism. The FEBS journal 33 32383312
2015 Study on Environmental Causes and SNPs of MTHFR, MS and CBS Genes Related to Congenital Heart Disease. PloS one 33 26035828
2020 LncRNA SNHG1 alleviated apoptosis and inflammation during ischemic stroke by targeting miR-376a and modulating CBS/H2S pathway. The International journal of neuroscience 32 32532171
2015 TLR4 upregulates CBS expression through NF-κB activation in a rat model of irritable bowel syndrome with chronic visceral hypersensitivity. World journal of gastroenterology 32 26229403
2020 Enhanced Stromal Cell CBS-H2S Production Promotes Estrogen-Stimulated Human Endometrial Angiogenesis. Endocrinology 31 32987401
2012 Novel structural arrangement of nematode cystathionine β-synthases: characterization of Caenorhabditis elegans CBS-1. The Biochemical journal 31 22240119
2024 ATF3-CBS signaling axis coordinates ferroptosis and tumorigenesis in colorectal cancer. Redox biology 29 38490069
2022 Overexpression of CBS/H2S inhibits proliferation and metastasis of colon cancer cells through downregulation of CD44. Cancer cell international 29 35172821
2012 Folding and activity of mutant cystathionine β-synthase depends on the position and nature of the purification tag: characterization of the R266K CBS mutant. Protein expression and purification 29 22333527
2019 CBS promoter hypermethylation increases the risk of hypertension and stroke. Clinics (Sao Paulo, Brazil) 28 30916171
2021 CBS-derived H2S facilitates host colonization of Vibrio cholerae by promoting the iron-dependent catalase activity of KatB. PLoS pathogens 27 34283874
2020 CBS and MAT2A improve methionine-mediated DNA synthesis through SAMTOR/mTORC1/S6K1/CAD pathway during embryo implantation. Cell proliferation 27 33179842
2019 Hyperhomocysteinemia induced endothelial progenitor cells dysfunction through hyper-methylation of CBS promoter. Biochemical and biophysical research communications 25 30683311
2013 Reduced response of Cystathionine Beta-Synthase (CBS) to S-Adenosylmethionine (SAM): Identification and functional analysis of CBS gene mutations in Homocystinuria patients. Journal of inherited metabolic disease 25 23974653
2010 Silencing mediated by the Schizosaccharomyces pombe HIRA complex is dependent upon the Hpc2-like protein, Hip4. PloS one 25 20976105
1996 Isolation and characterization of a delta-9 fatty acid desaturase gene from the oleaginous yeast Cryptococcus curvatus CBS 570. Yeast (Chichester, England) 25 8813759
2021 Vitamin B12 Attenuates Acute Pancreatitis by Suppressing Oxidative Stress and Improving Mitochondria Dysfunction via CBS/SIRT1 Pathway. Oxidative medicine and cellular longevity 23 34925701
2018 Overexpression of CBS and CSE genes affects lifespan, stress resistance and locomotor activity in Drosophila melanogaster. Aging 23 30408770
2015 Over-Expression of Rice CBS Domain Containing Protein, OsCBSX3, Confers Rice Resistance to Magnaporthe oryzae Inoculation. International journal of molecular sciences 23 26184180
1991 Cloning and disruption of the LEU2 gene of Kluyveromyces marxianus CBS 6556. Yeast (Chichester, England) 23 1803820
2016 Identification and Comparative Analysis of CBS Domain-Containing Proteins in Soybean (Glycine max) and the Primary Function of GmCBS21 in Enhanced Tolerance to Low Nitrogen Stress. International journal of molecular sciences 22 27128900
2024 Unveiling biological activities of biosynthesized starch/silver-selenium nanocomposite using Cladosporium cladosporioides CBS 174.62. BMC microbiology 21 38459502
2014 The association between the 844ins68 polymorphism in the CBS gene and breast cancer. Archives of medical science : AMS 21 25624861
2013 Identification and functional analysis of a novel PRKAG2 mutation responsible for Chinese PRKAG2 cardiac syndrome reveal an important role of non-CBS domains in regulating the AMPK pathway. Journal of cardiology 21 23778007
2018 Structural and functional insights into the unique CBS-CP12 fusion protein family in cyanobacteria. Proceedings of the National Academy of Sciences of the United States of America 20 29915055
2022 CBS-H2S axis preserves the intestinal barrier function by inhibiting COX-2 through sulfhydrating human antigen R in colitis. Journal of advanced research 19 36725190
2019 Accumulation of Tau Protein, Metabolism and Perfusion-Application and Efficacy of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) Imaging in the Examination of Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS). Frontiers in neurology 19 30837933
2022 Deletions of the cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) genes, involved in the control of hydrogen sulfide biosynthesis, significantly affect lifespan and fitness components of Drosophila melanogaster. Mechanisms of ageing and development 18 35247392
2020 Clinical Significance of CBS and CCL21 in Gallbladder Adenocarcinomas and Squamous Cell/Adenosquamous Carcinomas. Applied immunohistochemistry & molecular morphology : AIMM 18 32044878
2019 Estradiol-17β inhibits homocysteine mediated damage by promoting H2 S production via upregulating CBS and CSE expression in human umbilical vein endothelial cells. Journal of cellular biochemistry 18 31724756
2016 Endogenous CBS-H2S Pathway Contributes to the Development of CCI-Induced Neuropathic Pain. Neurochemical research 18 26961888
2024 Vitamin B6 alleviates chronic sleep deprivation-induced hippocampal ferroptosis through CBS/GSH/GPX4 pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 17 38599059
2023 Total flavones of Rhododendron induce the transformation of A1/A2 astrocytes via promoting the release of CBS-produced H2S. Phytomedicine : international journal of phytotherapy and phytopharmacology 17 36701996
2021 Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation. Genome biology 17 34074348
2019 Cystathionine β-synthase (CBS) deficiency suppresses erythropoiesis by disrupting expression of heme biosynthetic enzymes and transporter. Cell death & disease 17 31551410
2017 Analysis of MTHFR, CBS, Glutathione, Taurine, and Hydrogen Sulfide Levels in Retinas of Hyperhomocysteinemic Mice. Investigative ophthalmology & visual science 17 28384716
2017 DNA hypomethylation of CBS promoter induced by folate deficiency is a potential noninvasive circulating biomarker for colorectal adenocarcinomas. Oncotarget 17 28881655
2016 CO-CBS-H2 S Axis: From Vascular Mediator to Cancer Regulator. Microcirculation (New York, N.Y. : 1994) 17 26537442
2013 Gene-environment and gene-gene interactions of specific MTHFR, MTR and CBS gene variants in relation to homocysteine in black South Africans. Gene 17 23954866
2002 CBS 844ins68, MTHFR TT677 and EPCR 4031ins23 genotypes in patients with deep-vein thrombosis. Thrombosis research 17 12413583
2022 Rutin Inhibits the Progression of Osteoarthritis Through CBS-Mediated RhoA/ROCK Signaling. DNA and cell biology 16 35588172
2021 ADT-OH inhibits malignant melanoma metastasis in mice via suppressing CSE/CBS and FAK/Paxillin signaling pathway. Acta pharmacologica Sinica 16 34795411
2020 Genome-Wide Investigation and Expression Profiling Under Abiotic Stresses of a Soybean Unknown Function (DUF21) and Cystathionine-β-Synthase (CBS) Domain-Containing Protein Family. Biochemical genetics 16 32778975
2018 S-adenosylhomocysteine hydrolase over-expression does not alter S-adenosylmethionine or S-adenosylhomocysteine levels in CBS deficient mice. Molecular genetics and metabolism reports 16 30023284
2015 Cystathionine β-Synthase (CBS) Domain-containing Pyrophosphatase as a Target for Diadenosine Polyphosphates in Bacteria. The Journal of biological chemistry 16 26400082
2011 Identification and functional analyses of CBS alleles in Spanish and Argentinian homocystinuric patients. Human mutation 16 21520339
2008 Molecular gene cloning and overexpression of the phytase from Debaryomyces castellii CBS 2923. Protein expression and purification 16 18242101
2007 DNA methylation status is not impaired in treated cystathionine beta-synthase (CBS) deficient patients. Molecular genetics and metabolism 16 17336565
2023 Sodium hydrosulfide inhibits hemin-induced ferroptosis and lipid peroxidation in BV2 cells via the CBS/H2S system. Cellular signalling 15 36646297
2022 Homozygous whole body Cbs knockout in adult mice features minimal pathology during ageing despite severe homocysteinemia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 35315960
2021 H2 S catalysed by CBS regulates testosterone synthesis through affecting the sulfhydrylation of PDE. Journal of cellular and molecular medicine 15 33713531
2018 Mouse modeling and structural analysis of the p.G307S mutation in human cystathionine β-synthase (CBS) reveal effects on CBS activity but not stability. The Journal of biological chemistry 15 30030379
2021 Acute acrylonitrile exposure inhibits endogenous H2S biosynthesis in rat brain and liver: The role of CBS/3-MPST-H2S pathway in its astrocytic toxicity. Toxicology 14 33486070
2020 Association of maternal dietary intakes and CBS gene polymorphisms with congenital heart disease in offspring. International journal of cardiology 14 32800907
2018 Eight novel mutations of CBS gene in nine Chinese patients with classical homocystinuria. World journal of pediatrics : WJP 14 29508359
2012 Role of polymorphisms in factor V (FV Leiden), prothrombin, plasminogen activator inhibitor type-1 (PAI-1), methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) genes as risk factors for thrombophilias. Mini reviews in medicinal chemistry 14 22512572
2016 Lack of global epigenetic methylation defects in CBS deficient mice. Journal of inherited metabolic disease 13 27444757
2010 The CBS domain protein MJ0729 of Methanocaldococcus jannaschii binds DNA. FEBS letters 13 20934423
1998 Expression of TGFalpha autocrine activity in human colon carcinoma CBS cells is autoregulated and independent of exogenous epidermal growth factor. Journal of cellular physiology 13 9525476
2023 Activating transcription factor (ATF) 6 upregulates cystathionine β synthetase (CBS) expression and hydrogen sulfide (H2S) synthesis to ameliorate liver metabolic damage. European journal of medical research 12 38007457

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