Human cystathionine beta-synthase (CBS) is a PLP-dependent, heme-containing enzyme that catalyzes condensation of L-serine with L-homocysteine to form cystathionine, the first step of transsulfuration toward cysteine. It also uses cysteine with homocysteine to generate cystathionine and hydrogen sulfide. The principally cytoplasmic enzyme has a C-terminal regulatory region that binds S-adenosylmethionine and controls activity and stability; its reduced heme can bind NO and CO and modulate catalysis. CBS forms oligomeric assemblies, and human full-length protein can form regulated filaments. A sumoylated fraction has also been detected at the nuclear scaffold. Biallelic CBS deficiency causes classical homocystinuria through impaired homocysteine metabolism.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004122 cystathionine beta-synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Inherited cystathionine beta-synthase catalysis is the principal activity. Reason: The PAINT assertion represents a curated ancestral placement, not a pairwise donor vote. Human CBS directly catalyzes serine/homocysteine condensation; its own accession among the descendant evidence is legitimate, not circular. The ancestral node has not been re-curated here. |
| GO:0004122 cystathionine beta-synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Convergent electronic mappings identify the correct catalytic reaction. Reason: The EC, Rhea, domain and mouse-homology sources agree with the directly measured human reaction. Their exact combined source objects are preserved; no uninspected donor-specific assay is claimed. Supporting Evidence: |
| GO:0004122 cystathionine beta-synthase activity | IDA PMID:23981774 Characterization of two pathogenic mutations in cystathionin... | ACCEPT | Summary: Human CBS catalyzes cystathionine formation. Reason: Wild-type and pathogenic T87N/D234N proteins were compared for activity and assembly; mutant loss does not redefine the wild-type enzyme. Supporting Evidence: |
| GO:0004122 cystathionine beta-synthase activity | IDA PMID:22985361 Human cystathionine ฮฒ-synthase (CBS) contains two classes of... | ACCEPT | Summary: Human CBS catalyzes cystathionine formation. Reason: Functional measurements of human wild type and disease variants accompany SAM calorimetry and establish regulated CBS activity. Supporting Evidence: |
| GO:0004122 cystathionine beta-synthase activity | IDA PMID:24416422 Nitrite reductase activity and inhibition of HโS biogenesis ... | ACCEPT | Summary: Human CBS catalyzes cystathionine formation. Reason: The primary Methods directly assay cystathionine formation from radiolabeled serine and homocysteine, alongside the alternative H2S-producing reaction. Supporting Evidence: |
| GO:0004122 cystathionine beta-synthase activity | IDA PMID:7929220 Transsulfuration depends on heme in addition to pyridoxal 5'... | ACCEPT | Summary: Human CBS catalyzes cystathionine formation. Reason: The original biochemical study establishes a heme-containing, PLP-dependent human CBS enzyme. Its historical interpretation of heme necessity is not adopted as a universal catalytic requirement. Supporting Evidence: |
| GO:0004122 cystathionine beta-synthase activity | IDA PMID:18776696 Modulation of cystathionine beta-synthase activity by the Ar... | ACCEPT | Summary: Human CBS catalyzes cystathionine formation. Reason: Human Arg51/Arg224 mutations alter activity through communication between the heme environment and the PLP site; the wild-type reaction is directly described. Supporting Evidence: |
| GO:0004122 cystathionine beta-synthase activity | IDA PMID:19010420 Kinetic characterization of recombinant human cystathionine ... | ACCEPT | Summary: Human CBS catalyzes cystathionine formation. Reason: Recombinant human enzyme kinetics measure cystathionine production from the two substrates; bacterial expression does not make the assayed enzyme bacterial. Supporting Evidence: |
| GO:0020037 heme binding | EXP PMID:29410458 Heme interaction of the intrinsically disordered N-terminal ... | ACCEPT | Summary: The human N-terminal segment directly interacts with heme. Reason: NMR and heme-interaction experiments concern the intrinsically disordered 1โ40 peptide, not an independent complete catalytic enzyme. They corroborate the native proteinโs heme-binding capacity without establishing that this peptide alone reproduces the full heme pocket. Supporting Evidence: |
| GO:0020037 heme binding | IDA PMID:24515102 NO* binds human cystathionine ฮฒ-synthase quickly and tightly... | ACCEPT | Summary: The regulatory heme is experimentally characterized in human CBS. Reason: Static and stopped-flow spectroscopy of recombinant human CBS distinguish ferric, ferrous and gas-ligated heme states. This is a genuine cofactor interaction within the enzyme, not a separate core occupation. Supporting Evidence: |
| GO:0020037 heme binding | IDA PMID:7929220 Transsulfuration depends on heme in addition to pyridoxal 5'... | ACCEPT | Summary: CBS contains a noncovalently associated heme cofactor. Reason: The original purification establishes heme association together with PLP-dependent enzyme activity. Subsequent mechanistic work distinguishes regulatory/structural heme effects from the PLP chemistry; heme is not described here as universally indispensable for catalysis. |
| GO:0020037 heme binding | IMP PMID:18776696 Modulation of cystathionine beta-synthase activity by the Ar... | ACCEPT | Summary: Heme-pocket perturbations support functional heme association. Reason: Arg51 and Arg224 contact heme propionates in the structural interpretation, and their mutation alters human enzyme activity. This supports the native cofactor interaction without treating mutant phenotypes as a new activity. Supporting Evidence: |
| GO:0030170 pyridoxal phosphate binding | IDA PMID:7929220 Transsulfuration depends on heme in addition to pyridoxal 5'... | ACCEPT | Summary: PLP binding supports the defining CBS reaction. Reason: The directly studied human enzyme is PLP dependent. This cofactor is part of the catalytic mechanism and is integrated into the single metabolic core rather than made a separate physiological function. |
| GO:0030170 pyridoxal phosphate binding | IDA PMID:18776696 Modulation of cystathionine beta-synthase activity by the Ar... | ACCEPT | Summary: The PLP site is coupled to the heme environment. Reason: The human mutagenesis study describes PLP-dependent beta-replacement and effects propagated from heme-contacting residues to the PLP site. The annotation is consistent with the established bound catalytic cofactor. Supporting Evidence: |
| GO:1904047 S-adenosyl-L-methionine binding | IDA PMID:22985361 Human cystathionine ฮฒ-synthase (CBS) contains two classes of... | ACCEPT | Summary: SAM is a directly measured allosteric ligand. Reason: Human CBS calorimetry, functional assays and kinetic modeling demonstrate SAM binding and distinguish stabilization from activation. The ligand regulates the enzyme; ligand occupancy is not a second independent catalytic core. Supporting Evidence: |
| GO:0070026 nitric oxide binding | IDA PMID:24416422 Nitrite reductase activity and inhibition of HโS biogenesis ... | KEEP AS NON CORE | Summary: Reduced CBS heme binds NO during the nitrite reaction. Reason: Ferrous-nitrosyl CBS formation and inhibition are directly demonstrated in anaerobic recombinant-enzyme experiments. The NADPH/MSR system supports biochemical plausibility, but endogenous hypoxic signaling was proposed rather than directly demonstrated by these experiments. Supporting Evidence: |
| GO:0070026 nitric oxide binding | IDA PMID:24515102 NO* binds human cystathionine ฮฒ-synthase quickly and tightly... | KEEP AS NON CORE | Summary: Human ferrous CBS binds NO rapidly and tightly. Reason: The primary spectroscopy measures binding and dissociation of NO at the reduced heme. This is a conditional regulatory property of the metabolic enzyme, not evidence that CBS is a dedicated NO receptor in every cell. Supporting Evidence: |
| GO:0070025 carbon monoxide binding | IDA PMID:24515102 NO* binds human cystathionine ฮฒ-synthase quickly and tightly... | KEEP AS NON CORE | Summary: Reduced CBS heme also binds carbon monoxide. Reason: The primary gas-reactivity experiments directly compare CO and NO binding. CO-dependent inhibition belongs to conditional heme regulation; it does not warrant a separate physiological core. Supporting Evidence: |
| GO:0019825 oxygen binding | IDA PMID:24515102 NO* binds human cystathionine ฮฒ-synthase quickly and tightly... | MARK AS OVER ANNOTATED | Summary: The measured oxygen reaction is heme oxidation, not demonstrated oxygen occupancy. Reason: GO:0019825 requires binding of O2. The actual primary oxygen-reactivity Results report recovery of the ferric CBS spectrum after mixing ferrous CBS with oxygenated buffer, with superoxide-sensitive kinetics. That experiment establishes redox reactivity and does not resolve an O2-bound CBS state. Assigning oxygen-binding activity from this reaction overstates the demonstrated mechanism; this is not an absolute claim that no transient interaction can occur. The original experimental source and identifier remain intact. The quoted Results passage was read externally at https://pmc.ncbi.nlm.nih.gov/articles/PMC3961681/; the immutable publication cache remains abstract-only. Supporting Evidence: |
| GO:0050421 nitrite reductase (NO-forming) activity | IDA PMID:24416422 Nitrite reductase activity and inhibition of HโS biogenesis ... | KEEP AS NON CORE | Summary: Human CBS can reduce nitrite to NO in vitro. Reason: The primary anaerobic experiments directly establish this side chemistry using reduced enzyme and nitrite, including an NADPH/MSR reducing system. High experimental nitrite and reducing conditions, and the absence of a corresponding cellular flux measurement, limit physiological extrapolation. Retain the measured activity outside the defining transsulfuration core. Supporting Evidence: PMID:24416422 reduce nitrite and generate NO |
| GO:0003824 catalytic activity | IEA GO_REF:0000043 | MODIFY | Summary: The broad catalytic mapping can be made reaction specific. Reason: The keyword is chemically correct, but the measured human reaction is known precisely. Replace the generic molecular function with the existing cystathionine beta-synthase activity term; this is a refinement of this source assertion, not a NEW annotation. Proposed replacements: cystathionine beta-synthase activity Supporting Evidence: PMID:19010420 L-serine and L-homocysteine to form L-cystathionine |
| GO:0016829 lyase activity | IEA GO_REF:0000043 | MODIFY | Summary: The lyase mapping can be made reaction specific. Reason: CBS belongs to the lyase enzyme class, but generic lyase activity omits its experimentally established beta-replacement chemistry. The existing specific CBS activity gives a more informative molecular-function assertion. Proposed replacements: cystathionine beta-synthase activity Supporting Evidence: PMID:19010420 L-serine and L-homocysteine to form L-cystathionine |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: The metal-binding keyword reflects the heme-containing enzyme. Reason: The source is consistent with iron in the bound heme, but it is less informative than the measured heme and PLP interactions. It does not establish an additional free-metal sensing, transport or metalloenzyme function. Supporting Evidence: |
| GO:0072341 modified amino acid binding | IDA PMID:20031578 Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma... | UNDECIDED | Summary: The specific modified-amino-acid binding assay is unresolved. Reason: The available GWAS body links CBS-region variation with plasma homocysteine and discusses its known metabolic role, but the inspected text does not expose a direct binding experiment underlying this IDA row. The downloaded body lacks the complete original Methods and target supplementary material. Substrate chemistry alone is not substituted for that missing assay, and no miscitation or wrong-gene claim is made. The inspected current official GO tree places the separately established SAM-binding term GO:1904047 under cation binding and sulfur compound binding, not GO:0072341. A possible chemical relationship does not supply the missing original assay or establish ontology redundancy; this source-specific IDA remains unresolved. Supporting Evidence: |
| GO:0042803 protein homodimerization activity | IDA PMID:11483494 Structure of human cystathionine beta-synthase: a unique pyr... | ACCEPT | Summary: Human CBS has a directly observed dimeric assembly unit. Reason: The original structural experiment uses a 1โ413 human construct lacking the C-terminal SAM-regulatory domain and observes a dimer. It supports homodimerization capacity, without claiming that intact human CBS is exclusively dimeric. Full-length higher-order assembly is a separate structural question. The full-length human constructs in PMID:38575566 additionally form filaments from dimeric units; this supports the original homodimerization assertion without imposing a single oligomeric state. The reviewed UniProt subunit statement describes a homotetramer. These observations concern assembly states and constructs; retention of a dimerization activity does not assert a universal dimeric physiological stoichiometry. |
| GO:0042802 identical protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | ACCEPT | Summary: CBS self-association supports assembly of the enzyme. Reason: The human binary-interaction map supplies a CBSโCBS source edge, corroborated by the exact self-interaction entry in reviewed UniProt and direct human structural/biochemical assembly evidence. The individual screenโs target table has not been re-audited here; no particular variant effect or obligatory oligomer stoichiometry is inferred from this binary edge. |
| GO:0042802 identical protein binding | IPI PMID:19447967 Shifted Transversal Design smart-pooling for high coverage i... | ACCEPT | Summary: CBS self-association supports assembly of the enzyme. Reason: The smart-pooling human interaction map supplies a CBSโCBS source edge, corroborated by the exact self-interaction entry in reviewed UniProt and direct human structural/biochemical assembly evidence. The individual screenโs target table has not been re-audited here; no particular variant effect or obligatory oligomer stoichiometry is inferred from this binary edge. |
| GO:0042802 identical protein binding | IPI PMID:21900206 A directed protein interaction network for investigating int... | ACCEPT | Summary: CBS self-association supports assembly of the enzyme. Reason: The directed signaling-interaction network supplies a CBSโCBS source edge, corroborated by the exact self-interaction entry in reviewed UniProt and direct human structural/biochemical assembly evidence. The individual screenโs target table has not been re-audited here; no particular variant effect or obligatory oligomer stoichiometry is inferred from this binary edge. |
| GO:0042802 identical protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | ACCEPT | Summary: CBS self-association supports assembly of the enzyme. Reason: The proteome-scale human binary map supplies a CBSโCBS source edge, corroborated by the exact self-interaction entry in reviewed UniProt and direct human structural/biochemical assembly evidence. The individual screenโs target table has not been re-audited here; no particular variant effect or obligatory oligomer stoichiometry is inferred from this binary edge. |
| GO:0042802 identical protein binding | IPI PMID:25502805 A massively parallel pipeline to clone DNA variants and exam... | ACCEPT | Summary: CBS self-association supports assembly of the enzyme. Reason: The cloned-variant interaction pipeline supplies a CBSโCBS source edge, corroborated by the exact self-interaction entry in reviewed UniProt and direct human structural/biochemical assembly evidence. The individual screenโs target table has not been re-audited here; no particular variant effect or obligatory oligomer stoichiometry is inferred from this binary edge. |
| GO:0042802 identical protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | ACCEPT | Summary: CBS self-association supports assembly of the enzyme. Reason: The human variant-interaction study supplies a CBSโCBS source edge, corroborated by the exact self-interaction entry in reviewed UniProt and direct human structural/biochemical assembly evidence. The individual screenโs target table has not been re-audited here; no particular variant effect or obligatory oligomer stoichiometry is inferred from this binary edge. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: The CBSโFXR2 association is retained as non-core. Reason: This exact P51116 partner is preserved in the IPI source from human binary interaction mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | KEEP AS NON CORE | Summary: The CBSโFXR2 association is retained as non-core. Reason: This exact P51116 partner is preserved in the IPI source from the autism-focused human interaction network and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: The CBSโPSMA1 association is retained as non-core. Reason: This exact P25786 partner is preserved in the IPI source from proteome-scale human binary mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | UNDECIDED | Summary: The precise cross-species screen edge remains unverified. Reason: The paper experimentally maps humanโyeast interactions using yeast two-hybrid screening and pair retesting, so the foreign-species partner UniProtKB:P32449 is not itself a reason to reject the result. However, the CBS-specific entry, construct and pair-level control in the supplementary target table were not accessible in the inspected material, and reviewed UniProt does not independently corroborate this exact edge. Preserve the source while withholding a confident action or finer mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: The CBSโPSMA1 association is retained as non-core. Reason: This exact P25786 partner is preserved in the IPI source from a human variant-interaction survey and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The CBSโPIAS2 isoform 2 association is retained as non-core. Reason: This exact O75928-2 partner is preserved in the IPI source from the HuRI human binary map and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The CBSโFKBP6 association is retained as non-core. Reason: This exact O75344 partner is preserved in the IPI source from neurodegenerative-disease interaction mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17087506 Human cystathionine beta-synthase is a target for sumoylatio... | KEEP AS NON CORE | Summary: CBS association with RanBPM is directly named in the original study. Reason: The human CBS sumoylation study reports a yeast-two-hybrid interaction with RanBPM (the preserved RANBP9 partner), together with components of SUMO machinery. A proteinโs name does not make it a Ran GTPase or establish GTPase-binding activity by CBS. Retain the generic association without an inferred adaptor or signaling function. Supporting Evidence: |
| GO:0019899 enzyme binding | IPI PMID:17087506 Human cystathionine beta-synthase is a target for sumoylatio... | MODIFY | Summary: CBS binds the SUMO E3 ligase Pc2/CBX4. Reason: The human CBS study explicitly identifies Pc2/CBX4 among its yeast-two-hybrid interaction partners and reports dependence on the CBS C-terminal regulatory region. The exact source partner O00257 is a SUMO E3 ligase in the reviewed UniProt record. GO:0044389, ubiquitin-like protein ligase binding, therefore captures this association more precisely than generic enzyme binding and does not require ubiquitin-specific ligation. CBS is the interacting SUMO substrate; no ligase catalytic activity, modification process or core SUMO function is assigned to CBS. The cached abstract supports the named interaction, while detailed original construct and pairwise assay controls remain uninspected. Proposed replacements: ubiquitin-like protein ligase binding Supporting Evidence: PMID:17087506 PIAS1, PIAS3, Pc2 |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:17087506 Human cystathionine beta-synthase is a target for sumoylatio... | MODIFY | Summary: CBS binds the SUMO-conjugating E2 Ubc9/UBE2I. Reason: The exact source partner P63279 is Ubc9/UBE2I, explicitly named in the human CBS interaction study and independently identified as the SUMO E2 conjugating enzyme. GO:0044390 specifies ubiquitin-like protein conjugating enzyme binding and is a more informative fit than generic enzyme binding. The original GO:0031625 denotes ubiquitin-specific ligase binding; neither that substrate class nor a PIAS/Pc2 E3 identity is established for this Ubc9 edge. This refinement records CBS binding to its modifying enzyme, without assigning SUMO catalysis to CBS or asserting that Ubc9 can never support other SUMO-transferase behavior. Proposed replacements: ubiquitin-like protein conjugating enzyme binding Supporting Evidence: PMID:17087506 including Ubc9, PIAS1, PIAS3, Pc2, and RanBPM |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic localization is conserved and target supported. Reason: The IBA reflects a curated ancestral placement; the target among its descendant evidence is expected. Direct human localization and the cytosolic metabolic reaction support the assignment without reconstructing the ancestral node or inferring strength from donor count. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic cytoplasmic mapping is appropriate. Reason: Reviewed localization and the CBS-family mapping agree with direct human localization and its soluble metabolic role. The broad compartment remains biologically correct although the core is summarized more precisely in cytosol. |
| GO:0005737 cytoplasm | IDA PMID:23981774 Characterization of two pathogenic mutations in cystathionin... | ACCEPT | Summary: Wild-type human CBS is distributed in the cytoplasm. Reason: The original study compares wild type with T87N and D234N variants in expressed-protein localization experiments. Mutant aggregation/puncta are not generalized to wild-type CBS; the direct source supports its ordinary intracellular distribution. Supporting Evidence: |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1614524 | ACCEPT | Summary: The cystathionine-producing reaction is assigned to cytosol. Reason: The preserved Reactome-derived GOA assertion assigns this reaction to cytosol, consistent with independent human enzyme/localization evidence. The complete cached event summary describes the CBS reaction but does not itself give a compartment. Its historic tetramer wording, beta-lyase wording and separate CBSL database entry are not adopted as the exact enzyme identity, an exclusive assembly state or a second independently established human locus. |
| GO:0005829 cytosol | HDA PMID:16780588 Cell array-based intracellular localization screening reveal... | ACCEPT | Summary: Cytosolic residence is consistent with the localization survey and metabolic evidence. Reason: The human chromosome-21 localization survey used expressed constructs and organelle markers. Its CBS-specific image/target table was not independently inspected, so no detailed localization pattern is attributed to that table. The curatorโs cytosol assignment is retained because the exact compartment is independently supported by the curated reaction and known human cytoplasmic enzyme, rather than rejected from an abstract omission. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear residence is a documented conditional localization. Reason: The reviewed subcellular-location mapping is supported by the human SUMO study, which identifies nuclear-scaffold-associated sumoylated CBS. This does not relocate the principal transsulfuration reaction to the nucleus or establish a nuclear transcriptional activity. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:17087506 Human cystathionine beta-synthase is a target for sumoylatio... | KEEP AS NON CORE | Summary: Sumoylated human CBS can associate with the nuclear scaffold. Reason: This localization is explicitly reported in the original abstract. Full compartmental fractionation and construct details were not accessible; the directly stated observation supports a limited non-core localization rather than a new nuclear mechanism. Supporting Evidence: |
| GO:0006535 L-cysteine biosynthetic process from L-serine | IBA GO_REF:0000033 | ACCEPT | Summary: CBS performs a catalytic step in cysteine synthesis from serine. Reason: CBS converts serine and homocysteine to cystathionine, and cystathionine gamma-lyase subsequently releases cysteine. CBS therefore performs part of the biosynthesis rather than merely being required for it. The PAINT donor list includes diverse enzymes; the inherited process is supported by the human reaction without pretending that every descendant uses an identical pathway or that the IBD was independently inspected. |
| GO:0006535 L-cysteine biosynthetic process from L-serine | IEA GO_REF:0000002 | ACCEPT | Summary: The family-level biosynthetic process agrees with the human pathway. Reason: The broad PLP-enzyme domain by itself is not sufficient to distinguish every family reaction. Here direct human CBS chemistry establishes the serine-to-cystathionine step of cysteine synthesis, so the process mapping is independently supported. |
| GO:0019343 L-cysteine biosynthetic process via L-cystathionine | IEA GO_REF:0000002 | ACCEPT | Summary: Cysteine synthesis proceeds through the cystathionine intermediate. Reason: The CBS-family mapping captures the reaction that CBS itself performs: formation of cystathionine from serine and homocysteine. CTH catalyzes the subsequent cleavage; CBS is not claimed to perform that second step. |
| GO:0019344 L-cysteine biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: CBS catalytically participates in cysteine biosynthesis. Reason: Formation of cystathionine is a direct enzymatic contribution to the two-step transsulfuration route. The broader biosynthesis term is sound, while the final cysteine-releasing reaction belongs to CTH. |
| GO:0019344 L-cysteine biosynthetic process | IDA PMID:24416422 Nitrite reductase activity and inhibition of HโS biogenesis ... | ACCEPT | Summary: CBS catalytically participates in cysteine biosynthesis. Reason: Formation of cystathionine is a direct enzymatic contribution to the two-step transsulfuration route. The broader biosynthesis term is sound, while the final cysteine-releasing reaction belongs to CTH. |
| GO:0019346 transsulfuration | IEA GO_REF:0000107 | ACCEPT | Summary: CBS catalyzes the first step of transsulfuration. Reason: The rat orthology source is preserved, but acceptance does not rely only on transfer: direct human enzyme kinetics establish the same serine/homocysteine reaction. No specific uninspected rat experiment is described as read. Supporting Evidence: |
| GO:0050667 homocysteine metabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: CBS directly metabolizes homocysteine. Reason: Homocysteine is a substrate of the measured human cystathionine-forming reaction. This is direct metabolic work, not merely a secondary change in plasma concentration after perturbation. |
| GO:0050667 homocysteine metabolic process | IDA PMID:23981774 Characterization of two pathogenic mutations in cystathionin... | ACCEPT | Summary: CBS directly metabolizes homocysteine. Reason: Homocysteine is a substrate of the measured human cystathionine-forming reaction. This is direct metabolic work, not merely a secondary change in plasma concentration after perturbation. |
| GO:0050667 homocysteine metabolic process | IDA PMID:20031578 Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma... | ACCEPT | Summary: Homocysteine metabolism is correct, with the GWAS evidence kept distinct. Reason: The available study body associates CBS-region variation with plasma homocysteine; it is not itself a purified-enzyme assay. Nevertheless the annotated metabolic process is unambiguously established by independent human CBS kinetics. Retain the original IDA/source metadata without silently recoding it or claiming that the GWAS demonstrated the catalytic reaction. |
| GO:0050667 homocysteine metabolic process | IDA PMID:19010420 Kinetic characterization of recombinant human cystathionine ... | ACCEPT | Summary: CBS directly metabolizes homocysteine. Reason: Homocysteine is a substrate of the measured human cystathionine-forming reaction. This is direct metabolic work, not merely a secondary change in plasma concentration after perturbation. |
| GO:0043418 L-homocysteine catabolic process | IDA PMID:24416422 Nitrite reductase activity and inhibition of HโS biogenesis ... | ACCEPT | Summary: CBS consumes L-homocysteine in cystathionine synthesis. Reason: The human reaction directly uses L-homocysteine in transsulfuration. L-homocysteine catabolic process is both the preserved review label and the current official label for GO:0043418; the archived GOA uses a different shortened label for the same identifier. This is not a claim about which label is newer. The original term identifier and experimental source remain unchanged. |
| GO:0043418 L-homocysteine catabolic process | IDA PMID:18776696 Modulation of cystathionine beta-synthase activity by the Ar... | ACCEPT | Summary: CBS consumes L-homocysteine in cystathionine synthesis. Reason: The human reaction directly uses L-homocysteine in transsulfuration. L-homocysteine catabolic process is both the preserved review label and the current official label for GO:0043418; the archived GOA uses a different shortened label for the same identifier. This is not a claim about which label is newer. The original term identifier and experimental source remain unchanged. |
| GO:0006563 L-serine metabolic process | IDA PMID:19010420 Kinetic characterization of recombinant human cystathionine ... | ACCEPT | Summary: L-serine is directly metabolized by human CBS. Reason: The primary recombinant-human kinetic study measures serine-dependent cystathionine formation and also characterizes the reverse hydrolytic reaction. The forward physiological reaction directly supports this broad metabolic process. Supporting Evidence: |
| GO:0006565 L-serine catabolic process | IDA PMID:18776696 Modulation of cystathionine beta-synthase activity by the Ar... | UNDECIDED | Summary: Serine conversion is demonstrated, but its classification as serine catabolism remains unresolved. Reason: The original publisher Methods measure labeled-serine incorporation into cystathionine using purified full-length and truncated human CBS; the Results establish this synthetic reaction. The Discussion describes elimination to an aminoacrylate intermediate followed by homocysteine addition. GO:0006565 concerns breakdown of L-serine under amino-acid catabolism. Substrate consumption and an elimination step within synthesis do not by themselves settle that process classification, while retention of the carbon skeleton does not alone disprove it. Retain the original IDA assertion as UNDECIDED for this ontology boundary, without disputing the demonstrated CBS reaction or broader serine metabolism. Supporting Evidence: |
| GO:0006534 cysteine metabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: CBS connects cysteine synthesis and alternative cysteine utilization. Reason: The automated broad metabolic annotation agrees with catalytic participation in cysteine synthesis via cystathionine and the alternative cysteine/homocysteine reaction yielding H2S. The rule itself is not independently reconstructed. |
| GO:0019448 L-cysteine catabolic process | IDA PMID:15520012 Production of the neuromodulator H2S by cystathionine beta-s... | ACCEPT | Summary: CBS directly consumes cysteine in H2S-producing beta-replacement. Reason: The primary biochemical study compares cysteine/homocysteine condensation with cysteine-only hydrolysis and identifies the former as much more efficient under its tested conditions. Retain cysteine utilization without conflating CBS with the downstream cystathionine-cleaving enzyme. Supporting Evidence: |
| GO:0044272 sulfur compound biosynthetic process | IEA GO_REF:0000117 | ACCEPT | Summary: CBS directly synthesizes sulfur-containing metabolites. Reason: The ARBA term is broad but supported by CBS production of cystathionine and H2S. Acceptance rests on human catalytic evidence, not an assumed interpretation of the uninspected rule. |
| GO:0008652 amino acid biosynthetic process | IEA GO_REF:0000043 | ACCEPT | Summary: CBS contributes directly to amino-acid biosynthesis. Reason: The keyword-level process includes its formation of cystathionine in the cysteine-biosynthetic pathway. This remains broad source coverage; the core names the more specific pathway and reaction. Supporting Evidence: |
| GO:0070814 hydrogen sulfide biosynthetic process | IEA GO_REF:0000107 | ACCEPT | Summary: CBS can directly generate hydrogen sulfide. Reason: Human biochemical experiments establish cysteine/homocysteine beta-replacement yielding cystathionine and H2S. This directly supports the process even for the preserved rat-derived electronic/manual-transfer rows. It does not establish the relative contribution of CBS to H2S flux in every tissue or transfer every downstream H2S signaling phenotype to CBS. |
| GO:0070814 hydrogen sulfide biosynthetic process | IDA PMID:24416422 Nitrite reductase activity and inhibition of HโS biogenesis ... | ACCEPT | Summary: CBS can directly generate hydrogen sulfide. Reason: Human biochemical experiments establish cysteine/homocysteine beta-replacement yielding cystathionine and H2S. This directly supports the process even for the preserved rat-derived electronic/manual-transfer rows. It does not establish the relative contribution of CBS to H2S flux in every tissue or transfer every downstream H2S signaling phenotype to CBS. |
| GO:0070814 hydrogen sulfide biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: CBS can directly generate hydrogen sulfide. Reason: Human biochemical experiments establish cysteine/homocysteine beta-replacement yielding cystathionine and H2S. This directly supports the process even for the preserved rat-derived electronic/manual-transfer rows. It does not establish the relative contribution of CBS to H2S flux in every tissue or transfer every downstream H2S signaling phenotype to CBS. |
| GO:0070814 hydrogen sulfide biosynthetic process | IDA PMID:15520012 Production of the neuromodulator H2S by cystathionine beta-s... | ACCEPT | Summary: CBS can directly generate hydrogen sulfide. Reason: Human biochemical experiments establish cysteine/homocysteine beta-replacement yielding cystathionine and H2S. This directly supports the process even for the preserved rat-derived electronic/manual-transfer rows. It does not establish the relative contribution of CBS to H2S flux in every tissue or transfer every downstream H2S signaling phenotype to CBS. |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Human CBS assembly responds to nutrient availability in a defined cell system. Reason: The preserved electronic rat transfer is independently corroborated by PMID:38575566: transiently expressed full-length human CBS with a C-terminal Flag-mKO2 tag changes its fluorescence assembly pattern in PC-3 cells after eight hours of nutrient manipulation. Methionine depletion alone reduces the filament-like pattern, and SAM supplementation restores it; SAM addition to complete medium has no significant effect. This directly supports a bounded nutrient-responsive enzyme-assembly state, retained outside the principal catalytic core. The measurements concern tagged-protein fluorescence morphology, not endogenous filament ultrastructure or a demonstrated change in cellular metabolic flux. The original rat dietary-casein donor experiment is not silently recoded as this human assay. Supporting Evidence: PMID:38575566 Methionine depletion alone sufficiently reduced the filamentous pattern |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | UNDECIDED | Summary: The context and transfer of CBS-dependent anti-apoptotic protection remain unresolved. Reason: Official donor provenance links the rat annotation to a hypoxia/H2S study. Its primary abstract describes SH-SY5Y cells, pharmacological H2S donation and CBS-overexpression-associated protection, but does not resolve the expression construct species or full target controls. The human cell line alone does not establish the identity of the expressed CBS. Retain uncertainty about this specific transfer rather than remove the assertion merely because it is downstream of metabolism. |
| GO:0071456 cellular response to hypoxia | IEA GO_REF:0000107 | UNDECIDED | Summary: The hypoxia-response source has positive evidence but an unresolved transfer boundary. Reason: The official donor trace and primary abstract support a hypoxia/H2S experimental context, including altered endogenous H2S and CBS overexpression. The exact CBS construct, perturbation controls and human orthology-transfer scope were not verified in the original full experiment. Response terms can include regulated expression and activity; the annotation is not rejected simply because CBS is metabolic rather than an oxygen sensor. |
| GO:0042262 DNA protection | IMP PMID:24534463 Homocysteine contribution to DNA damage in cystathionine ฮฒ-s... | UNDECIDED | Summary: The DNA-protection interpretation of the patient study remains bounded. Reason: The complete available abstract reports comet-assay damage in treated CBS-deficient patients and concentration-dependent damage after homocysteine exposure to white blood cells. This supports disease-associated genotoxic stress, but the original full experiments and the precise protective mechanism were not accessible. Keep the existing IMP assertion unresolved rather than label it wrong or infer a direct DNA-binding/repair role for CBS. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: The CBSโPRKAG1 association is retained as non-core. Reason: This exact P54619 partner is preserved in the IPI source from proteome-scale human binary mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: The CBSโUBASH3A association is retained as non-core. Reason: This exact P57075 partner is preserved in the IPI source from proteome-scale human binary mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: The CBSโEHHADH association is retained as non-core. Reason: This exact Q08426 partner is preserved in the IPI source from proteome-scale human binary mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: The CBSโPIN1 association is retained as non-core. Reason: This exact Q13526 partner is preserved in the IPI source from proteome-scale human binary mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: The CBSโUBE2I association is retained as non-core. Reason: This exact Q7KZS0 partner is preserved in the IPI source from proteome-scale human binary mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | UNDECIDED | Summary: The precise cross-species screen edge remains unverified. Reason: The paper experimentally maps humanโyeast interactions using yeast two-hybrid screening and pair retesting, so the foreign-species partner UniProtKB:P32502 is not itself a reason to reject the result. However, the CBS-specific entry, construct and pair-level control in the supplementary target table were not accessible in the inspected material, and reviewed UniProt does not independently corroborate this exact edge. Preserve the source while withholding a confident action or finer mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | UNDECIDED | Summary: The precise cross-species screen edge remains unverified. Reason: The paper experimentally maps humanโyeast interactions using yeast two-hybrid screening and pair retesting, so the foreign-species partner UniProtKB:P38340 is not itself a reason to reject the result. However, the CBS-specific entry, construct and pair-level control in the supplementary target table were not accessible in the inspected material, and reviewed UniProt does not independently corroborate this exact edge. Preserve the source while withholding a confident action or finer mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | UNDECIDED | Summary: The precise cross-species screen edge remains unverified. Reason: The paper experimentally maps humanโyeast interactions using yeast two-hybrid screening and pair retesting, so the foreign-species partner UniProtKB:P39518 is not itself a reason to reject the result. However, the CBS-specific entry, construct and pair-level control in the supplementary target table were not accessible in the inspected material, and reviewed UniProt does not independently corroborate this exact edge. Preserve the source while withholding a confident action or finer mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | UNDECIDED | Summary: The precise cross-species screen edge remains unverified. Reason: The paper experimentally maps humanโyeast interactions using yeast two-hybrid screening and pair retesting, so the foreign-species partner UniProtKB:Q02821 is not itself a reason to reject the result. However, the CBS-specific entry, construct and pair-level control in the supplementary target table were not accessible in the inspected material, and reviewed UniProt does not independently corroborate this exact edge. Preserve the source while withholding a confident action or finer mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | UNDECIDED | Summary: The precise cross-species screen edge remains unverified. Reason: The paper experimentally maps humanโyeast interactions using yeast two-hybrid screening and pair retesting, so the foreign-species partner UniProtKB:Q07379 is not itself a reason to reject the result. However, the CBS-specific entry, construct and pair-level control in the supplementary target table were not accessible in the inspected material, and reviewed UniProt does not independently corroborate this exact edge. Preserve the source while withholding a confident action or finer mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | UNDECIDED | Summary: The precise cross-species screen edge remains unverified. Reason: The paper experimentally maps humanโyeast interactions using yeast two-hybrid screening and pair retesting, so the foreign-species partner UniProtKB:Q12259 is not itself a reason to reject the result. However, the CBS-specific entry, construct and pair-level control in the supplementary target table were not accessible in the inspected material, and reviewed UniProt does not independently corroborate this exact edge. Preserve the source while withholding a confident action or finer mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: The CBSโFXR2 association is retained as non-core. Reason: This exact P51116 partner is preserved in the IPI source from a human variant-interaction survey and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: The CBSโUBASH3A association is retained as non-core. Reason: This exact P57075 partner is preserved in the IPI source from a human variant-interaction survey and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: The CBSโEHHADH association is retained as non-core. Reason: This exact Q08426 partner is preserved in the IPI source from a human variant-interaction survey and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: The CBSโPIN1 association is retained as non-core. Reason: This exact Q13526 partner is preserved in the IPI source from a human variant-interaction survey and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The CBSโUBE2I association is retained as non-core. Reason: This exact Q7KZS0 partner is preserved in the IPI source from the HuRI human binary map and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The CBSโZMYM5 isoform 2 association is retained as non-core. Reason: This exact Q9UJ78-2 partner is preserved in the IPI source from the HuRI human binary map and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The CBSโFYN association is retained as non-core. Reason: This exact P06241 partner is preserved in the IPI source from neurodegenerative-disease interaction mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The CBSโPRKACA association is retained as non-core. Reason: This exact P17612 partner is preserved in the IPI source from neurodegenerative-disease interaction mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The CBSโGAL association is retained as non-core. Reason: This exact P22466 partner is preserved in the IPI source from neurodegenerative-disease interaction mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The CBSโCTNNB1 association is retained as non-core. Reason: This exact P35222 partner is preserved in the IPI source from neurodegenerative-disease interaction mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The CBSโHTT association is retained as non-core. Reason: This exact P42858 partner is preserved in the IPI source from neurodegenerative-disease interaction mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The CBSโCYTH1 association is retained as non-core. Reason: This exact Q15438 partner is preserved in the IPI source from neurodegenerative-disease interaction mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The CBSโKAT5 isoform 2 association is retained as non-core. Reason: This exact Q92993-2 partner is preserved in the IPI source from neurodegenerative-disease interaction mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The CBSโCAMK2A association is retained as non-core. Reason: This exact Q9UQM7 partner is preserved in the IPI source from neurodegenerative-disease interaction mapping and corroborated by the reviewed human CBS UniProt interaction record. The complete source abstract was read, but the individual pairโs original target table and construct controls were not independently rechecked. This convergent physical-edge evidence supports a bounded generic association; partner identity alone does not establish a finer domain-binding activity, CBS regulation of the partner, or a physiological pathway role. Supporting Evidence: |
| GO:0019899 enzyme binding | IPI PMID:17087506 Human cystathionine beta-synthase is a target for sumoylatio... | MODIFY | Summary: CBS binds the SUMO E3 ligase PIAS1. Reason: The human CBS study explicitly identifies PIAS1 among its yeast-two-hybrid interaction partners and reports dependence on the CBS C-terminal regulatory region. The exact source partner O75925 is a SUMO E3 ligase in the reviewed UniProt record. GO:0044389, ubiquitin-like protein ligase binding, therefore captures this association more precisely than generic enzyme binding and does not require ubiquitin-specific ligation. CBS is the interacting SUMO substrate; no ligase catalytic activity, modification process or core SUMO function is assigned to CBS. The cached abstract supports the named interaction, while detailed original construct and pairwise assay controls remain uninspected. Proposed replacements: ubiquitin-like protein ligase binding Supporting Evidence: PMID:17087506 PIAS1, PIAS3, Pc2 |
| GO:0019899 enzyme binding | IPI PMID:17087506 Human cystathionine beta-synthase is a target for sumoylatio... | MODIFY | Summary: CBS binds the SUMO E3 ligase PIAS3. Reason: The human CBS study explicitly identifies PIAS3 among its yeast-two-hybrid interaction partners and reports dependence on the CBS C-terminal regulatory region. The exact source partner Q9Y6X2 is a SUMO E3 ligase in the reviewed UniProt record. GO:0044389, ubiquitin-like protein ligase binding, therefore captures this association more precisely than generic enzyme binding and does not require ubiquitin-specific ligation. CBS is the interacting SUMO substrate; no ligase catalytic activity, modification process or core SUMO function is assigned to CBS. The cached abstract supports the named interaction, while detailed original construct and pairwise assay controls remain uninspected. Proposed replacements: ubiquitin-like protein ligase binding Supporting Evidence: PMID:17087506 PIAS1, PIAS3, Pc2 |
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Download this section (compressed HTML)Q: How do endogenous human CBS filament assembly, SAM levels and catalytic flux vary across tissues and nutrient states?
Q: Which original experiment supports modified-amino-acid binding in the homocysteine GWAS annotation, and does oxygen binding require an O2-bound state rather than heme oxidation?
Q: Which target constructs and controls support the CBSโyeast protein screen edges and the transferred rat hypoxia/apoptosis assertions?
Q: How does SUMO-dependent nuclear localization alter CBS activity or other molecular interactions without assigning the SUMO machineryโs catalytic role to its substrate?
Q: Does GO:0006565 include the CBS beta-replacement step within cystathionine synthesis, or does its serine-catabolism scope require a distinct degradative pathway beyond demonstrated substrate conversion?
Experiment: Measure endogenous CBS assembly and transsulfuration/H2S flux together during nutrient perturbation, with catalytic and filament-interface controls that distinguish assembly effects from protein abundance.
Experiment: Validate selected CBS screen interactions with reciprocal endogenous assays and domain/isoform controls before assigning specific regulatory or adaptor mechanisms.
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