{"schema":"https://ver.cy/schemas/card/1.0.0","id":"vr.tr.citrullination","code":"thing-q68581","url":"https://ver.cy/models/thing/q68581/","name":"citrullination","alternateNames":[],"kind":"thing","status":"published","version":"0.1.0-research.1","language":"en","classifiers":{"family":"Thing Registry","category":"Activities and processes","entryKind":"thing","plane":"ACT","domain":["ACT.PRC"],"industry":[],"navPath":"","tags":[],"facets":{}},"whatItIs":"Citrullination is the enzymatic conversion of protein-bound arginine residues into citrulline residues by peptidylarginine deiminases, a post-translational modification that removes the side chain's positive charge.","purpose":"Enable an AI agent to recognize, assess evidence for, and plan investigation of citrullination as a site-specific biochemical modification of protein-bound arginine.","scope":{"in":["Conversion of protein- or peptide-bound arginine residues into citrulline residues","Substrate identity, sequence position, and modification occupancy","Catalyst attribution and conditions supporting a particular reaction","Detection, site localization, quantification, and artifact assessment","Experimentally supported molecular consequences and process perturbations"],"out":["Free citrulline metabolism, transport, and supplementation","Standalone models of protein-arginine deiminase enzymes","Complete models of substrate proteins and their other modifications","Lysine carbamylation producing homocitrulline","Diagnosis or treatment of diseases associated with citrullinated proteins","Complete models of antibody responses, chromatin regulation, or extracellular trap formation"],"boundaries":[]},"distinguishingFeatures":["The defining substrate is an arginine residue in a protein or peptide, and the corresponding product residue is citrulline; free-arginine metabolism falls outside this boundary. See [NCBI MeSH](https://www.ncbi.nlm.nih.gov/mesh/2023542).","A candidate site must map to arginine in the specified reference sequence; an assignment to asparagine or glutamine instead raises deamidation as an alternative.","A mass increase of approximately 0.984016 Da supports a candidate assignment but cannot independently distinguish citrullination from asparagine or glutamine deamidation. See [primary proteomics study](https://pmc.ncbi.nlm.nih.gov/articles/PMC6030718/).","The record must distinguish direct evidence for a modified residue from enzyme expression, antibody reactivity, or a disease association used as indirect evidence.","A modification assignment must distinguish arginine-to-citrulline conversion from lysine-to-homocitrulline carbamylation, even when detection reagents recognize related chemical groups."],"structure":{"bundles":[{"id":"reaction-identity","name":"Reaction identity","description":"Establishes whether an observation represents conversion of peptidylarginine to peptidylcitrulline.","layers":[{"id":"substrate-product-continuity","name":"Substrate-product continuity","description":"Connects an arginine-containing substrate to its corresponding citrulline-containing product.","findings":[{"id":"residue-conversion-criterion","name":"Residue conversion criterion","description":"The defining event is conversion of arginine residues in proteins into citrulline residues by protein-arginine deiminases. See [NCBI MeSH](https://www.ncbi.nlm.nih.gov/mesh/2023542).","questions":[{"text":"Which substrate sequence and arginine position define the proposed conversion?","id":"residue-conversion-criterion-q01","kind":"definition"},{"text":"What evidence identifies citrulline at that position in the product?","id":"residue-conversion-criterion-q02","kind":"measurement"}]}]},{"id":"neighboring-reactions","name":"Neighboring reactions","description":"Separates citrullination from chemically or analytically similar processes.","findings":[{"id":"alternative-modification-check","name":"Alternative modification check","description":"A reaction assignment must explicitly evaluate whether the observed result instead concerns free-amino-acid metabolism, deamidation, or carbamylation.","questions":[{"text":"Does the evidence concern a protein-bound arginine rather than free arginine or citrulline?","id":"alternative-modification-check-q01","kind":"boundary"},{"text":"Which residue-specific evidence excludes deamidation or lysine carbamylation as the explanation?","id":"alternative-modification-check-q02","kind":"boundary"}]}]}]},{"id":"catalysis-and-setting","name":"Catalysis and setting","description":"Records the enzyme, substrate access, and conditions under which conversion is proposed to occur.","layers":[{"id":"enzyme-attribution","name":"Enzyme attribution","description":"Assesses the evidence connecting a particular catalyst to the observed site.","findings":[{"id":"catalyst-evidence","name":"Catalyst evidence","description":"Catalyst identity should be recorded with its evidential basis, distinguishing co-occurrence from direct conversion or controlled perturbation.","questions":[{"text":"Which enzyme and organism are implicated, and which experiment supports that attribution?","id":"catalyst-evidence-q01","kind":"provenance"},{"text":"What catalytic-loss, depletion, or rescue control would distinguish enzyme activity from an indirect effect?","id":"catalyst-evidence-q02","kind":"action"}]}]},{"id":"reaction-environment","name":"Reaction environment","description":"Captures the physical and biochemical setting of substrate conversion.","findings":[{"id":"condition-and-access-record","name":"Conditions and substrate access","description":"Record compartment, substrate accessibility, and experimental conditions; requirements established for one catalyst or preparation must not be assumed for every setting.","questions":[{"text":"Where and when could the proposed enzyme encounter the substrate site?","id":"condition-and-access-record-q01","kind":"boundary"},{"text":"What pH, temperature, ion conditions, and exposure time were measured or imposed?","id":"condition-and-access-record-q02","kind":"measurement"}]}]}]},{"id":"analytical-identification","name":"Analytical identification","description":"Evaluates whether analytical signals establish citrullination and localize it to the claimed residue.","layers":[{"id":"mass-spectrometric-localization","name":"Mass-spectrometric localization","description":"Tests peptide identity, residue localization, and competing spectral assignments.","findings":[{"id":"mass-shift-is-insufficient","name":"Mass shift is insufficient","description":"Deamidation and incorrect monoisotopic peak assignment can generate false citrullination identifications; a candidate therefore needs supporting fragmentation and assignment checks. See [primary analytical study](https://pmc.ncbi.nlm.nih.gov/articles/PMC8628552/).","questions":[{"text":"Which fragment ions localize the modification to arginine rather than a nearby asparagine or glutamine?","id":"mass-shift-is-insufficient-q01","kind":"measurement"},{"text":"How were monoisotopic selection, alternative peptide assignments, and modification-specific error rates evaluated?","id":"mass-shift-is-insufficient-q02","kind":"measurement"}]}]},{"id":"orthogonal-assay-evidence","name":"Orthogonal assay evidence","description":"Interprets antibody, chemical-labeling, and reference-standard results at their demonstrated specificity.","findings":[{"id":"assay-resolution-limit","name":"Assay resolution limit","description":"Record whether an assay establishes sample-level reactivity, a modified protein, or a particular residue; these evidence levels are not interchangeable.","questions":[{"text":"What does the reagent detect, and which unmodified or alternatively modified controls establish its specificity?","id":"assay-resolution-limit-q01","kind":"measurement"},{"text":"Would a matched synthetic peptide or an independent detection method resolve the remaining assignment ambiguity?","id":"assay-resolution-limit-q02","kind":"action"}]}]}]},{"id":"extent-and-sample-history","name":"Extent and sample history","description":"Separates modification occupancy and change over time from assay intensity and preparation effects.","layers":[{"id":"occupancy-and-comparison","name":"Occupancy and comparison","description":"Defines the denominator and analytical limits of quantitative claims.","findings":[{"id":"quantitative-denominator","name":"Quantitative denominator","description":"Site occupancy requires a justified estimate of the relevant substrate population; modified-peptide intensity alone should be recorded as signal rather than occupancy.","questions":[{"text":"Is the reported quantity site occupancy, modified-peptide abundance, total citrulline signal, or reaction rate?","id":"quantitative-denominator-q01","kind":"definition"},{"text":"How are substrate abundance, recovery, response differences, and undetected values handled?","id":"quantitative-denominator-q02","kind":"measurement"}]}]},{"id":"collection-to-analysis","name":"Collection to analysis","description":"Tracks handling steps that affect whether a modification can be attributed to the original sample.","findings":[{"id":"conversion-timing-control","name":"Conversion timing control","description":"Collection, storage, lysis, incubation, and quenching must be documented when the timing of conversion matters.","questions":[{"text":"What interval and conditions separated collection from effective reaction quenching?","id":"conversion-timing-control-q01","kind":"provenance"},{"text":"Which immediate-quench or handling-time control would test whether conversion occurred after collection?","id":"conversion-timing-control-q02","kind":"action"}]}]}]},{"id":"consequences-and-intervention","name":"Consequences and intervention","description":"Connects a verified modification to tested molecular effects and interpretable experimental actions.","layers":[{"id":"site-specific-effects","name":"Site-specific effects","description":"Tests consequences at a defined residue, substrate, and modification extent.","findings":[{"id":"effect-attribution","name":"Effect attribution","description":"Record the measured effect and the comparison that supports attribution to citrullination, including other modifications or experimental differences that remain confounded.","questions":[{"text":"What change in binding, activity, structure, proteolysis, or recognition was measured for the specified modified substrate?","id":"effect-attribution-q01","kind":"measurement"},{"text":"Does the comparison isolate citrullination at this site, or could other sites and treatment effects explain the result?","id":"effect-attribution-q02","kind":"boundary"}]}]},{"id":"perturbation-interpretation","name":"Perturbation interpretation","description":"Defines what intervention results can establish about the process.","findings":[{"id":"process-change-versus-phenotype","name":"Process change versus phenotype","description":"An intervention should establish its effect on citrullination separately from downstream outcomes; a phenotypic response alone does not demonstrate modification-dependent causality.","questions":[{"text":"Which direct modification readout will verify that the perturbation changed citrullination?","id":"process-change-versus-phenotype-q01","kind":"action"},{"text":"What complementary perturbation or rescue could distinguish citrullination-dependent effects from off-target or substrate-abundance effects?","id":"process-change-versus-phenotype-q02","kind":"action"}]}]}]},{"id":"evidence-and-external-alignment","name":"Evidence and external alignment","description":"What the world already says about this thing, gathered so the model can be checked against it.","layers":[{"id":"reported-evidence","name":"Reported evidence","description":"Findings from the breadth pass, kept separate from the structural claims.","findings":[{"id":"evidence-confidence-notes","name":"Check these first","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these check these first hold for the sense of citrullination this model covers, and on what evidence?","id":"evidence-confidence-notes-q01","kind":"provenance"}]},{"id":"evidence-kinds","name":"Kinds and varieties","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these kinds and varieties hold for the sense of citrullination this model covers, and on what evidence?","id":"evidence-kinds-q01","kind":"provenance"}]},{"id":"evidence-real-world-use","name":"Real-world use","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these real-world use hold for the sense of citrullination this model covers, and on what evidence?","id":"evidence-real-world-use-q01","kind":"provenance"}]},{"id":"evidence-measurements","name":"Typical measurements","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these typical measurements hold for the sense of citrullination this model covers, and on what evidence?","id":"evidence-measurements-q01","kind":"provenance"}]},{"id":"evidence-failure-modes-and-hazards","name":"Failure modes and hazards","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these failure modes and hazards hold for the sense of citrullination this model covers, and on what evidence?","id":"evidence-failure-modes-and-hazards-q01","kind":"provenance"}]},{"id":"evidence-neighbours","name":"Neighbouring kinds and how to tell them apart","description":"Recalled without web access and unsourced; every item is a lead to verify.","questions":[{"text":"Which of these neighbouring kinds and how to tell them apart hold for the sense of citrullination this model covers, and on what evidence?","id":"evidence-neighbours-q01","kind":"provenance"}]}]}]}]},"agentConduct":{"may":["Explain citrullination and its role in disease from scientific sources.","Report antibody test results to the clinician who ordered them."],"mustNot":["Diagnose rheumatoid arthritis or other diseases from a test result.","Promote unproven treatments or supplements that claim to block citrullination.","Share a person's test results beyond their care team."],"requiresHuman":["Any treatment decision based on related test results."]},"ethics":{"considerations":["Autoimmune disease affects quality of life; misinformation can delay real treatment.","Test results are private health data."],"affectedParties":["Patients with autoimmune disease","Researchers"]},"owners":{"steward":"Nobody owns the process; the treating clinician answers for its use in a patient's care.","roles":[],"masterSystems":[]},"relations":[{"target":"Q22276401","type":"parent","note":"registry parent class"}],"interaction":{"identity":{"applicability":"required","items":["Vercy registry: vr.tr.citrullination","Wikidata: Q68581 (https://www.wikidata.org/wiki/Q68581)"]},"properties":{"applicability":"not-applicable","items":["Substrate and residue coordinate: Protein accession, organism, sequence version, isoform, arginine position, and observed peptide","Catalyst attribution: Enzyme identity and organism; directly demonstrated, perturbation-supported, inferred, or unknown","Reaction setting: Purified system, cultured cells, tissue, extracellular sample, or other explicitly described setting","Site occupancy: Fraction or percentage of substrate molecules modified at a specified site, with denominator and uncertainty","Reaction conditions: Temperature in °C, duration in seconds or minutes, pH, and relevant reagent or ion concentrations in mol/L","Site assignment confidence: Candidate, localized, independently corroborated, ambiguous, or rejected; accompanied by method-specific evidence","Modification timing: Pre-existing in sample, formed during experimental treatment, potentially formed during handling, or unresolved","Functional consequence support: Not tested, associated, perturbation-supported, or directly tested at the specified site"]},"recognition":{"applicability":"not-applicable","items":[]},"capabilities":{"applicability":"required","items":["Map a candidate citrullination event to an explicit substrate sequence and residue.","Reject or flag assignments that lack site localization or retain plausible alternative explanations.","Compare modification extent across matched conditions while accounting for substrate abundance.","Select controls that distinguish catalyst involvement, sample-handling conversion, and analytical artifacts.","Plan a targeted experiment to test a proposed molecular consequence.","Link supported modification events to neighboring protein, enzyme, and disease models without treating association as causation."]},"hazards":{"applicability":"required","items":["Incorrectly assigning a modification to citrullination can produce false claims about protein function or biological mechanisms.","Treating evidence of citrullination as sufficient to establish a disease diagnosis can lead to inappropriate clinical conclusions.","Uncontrolled sample changes can distort measured citrullination and undermine comparisons between experiments."]},"interfaces":{"applicability":"required","items":["The Enzyme Commission classification maintained by the International Union of Biochemistry and Molecular Biology assigns peptidyl-arginine deiminase to EC 3.5.3.15."]},"context":{"applicability":"required","items":["Citrullination is studied in protein biochemistry to understand how modification of arginine residues changes protein charge, interactions and function.","It is encountered in research on chromatin regulation, immune activity and autoimmune disease.","Site-specific investigations use analytical evidence to distinguish citrullinated residues from other modifications and measurement artifacts."]}},"sources":[{"title":"Wikidata item Q68581: citrullination","url":"https://www.wikidata.org/wiki/Q68581","note":"identity and sense of the item"},{"title":"Wikipedia: Citrullination","url":"https://en.wikipedia.org/wiki/Citrullination","note":"general description of the item"}],"openQuestions":["Which catalyst families and organism-specific reaction constraints must be represented beyond the initially researched examples?","What minimum evidence should qualify a citrullinated site as independently corroborated across different analytical platforms?","Which reported substrate sites remain supported after explicit reassessment of deamidation and isotope-selection alternatives?","For each biological setting, what fraction of observed modification pre-exists collection rather than arising during handling?","Which proposed functional consequences have been demonstrated at defined sites and measured occupancies rather than inferred from broad enzyme perturbation?"],"resources":{"spec":"/models/things/publications/thing-q68581/spec.json"},"provenance":{"origin":"thing registry research (pass 2)","builtFrom":["models/things/publications/thing-q68581/spec.json"],"providers":["Codex"],"researchStatus":"unreviewed","generatedAt":"2026-09-12T08:42:53Z","builder":"tools/build_cards.py@1.0.0"},"completeness":{"sections":{"classifiers":"filled","whatItIs":"filled","purpose":"filled","distinguishingFeatures":"filled","structure":"filled","agentConduct":"filled","ethics":"filled","owners":"filled","relations":"filled","interaction.identity":"filled","interaction.properties":"not-applicable","interaction.recognition":"not-applicable","interaction.capabilities":"filled","interaction.hazards":"filled","interaction.interfaces":"filled","interaction.context":"filled","sources":"filled"},"notes":{"_gate":"Published through the thing publication gate 1.0 on 2026-10-07T10:10:32+00:00: completeness 1.00; sense: Wikidata description; 2 live sources; review by codex: pass","interaction.properties":"Plane ACT: no invented physical properties.","interaction.recognition":"Citrullination is a molecular reaction that cannot be identified by unaided visual inspection."},"score":1.0}}