citrullination

Residue conversion criterion

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).

1. Which substrate sequence and arginine position define the proposed conversion? definition
2. What evidence identifies citrulline at that position in the product? measurement

Alternative modification check

A reaction assignment must explicitly evaluate whether the observed result instead concerns free-amino-acid metabolism, deamidation, or carbamylation.

1. Does the evidence concern a protein-bound arginine rather than free arginine or citrulline? boundary
2. Which residue-specific evidence excludes deamidation or lysine carbamylation as the explanation? boundary

Catalyst evidence

Catalyst identity should be recorded with its evidential basis, distinguishing co-occurrence from direct conversion or controlled perturbation.

1. Which enzyme and organism are implicated, and which experiment supports that attribution? provenance
2. What catalytic-loss, depletion, or rescue control would distinguish enzyme activity from an indirect effect? action

Conditions and substrate access

Record compartment, substrate accessibility, and experimental conditions; requirements established for one catalyst or preparation must not be assumed for every setting.

1. Where and when could the proposed enzyme encounter the substrate site? boundary
2. What pH, temperature, ion conditions, and exposure time were measured or imposed? measurement

Mass shift is insufficient

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/).

1. Which fragment ions localize the modification to arginine rather than a nearby asparagine or glutamine? measurement
2. How were monoisotopic selection, alternative peptide assignments, and modification-specific error rates evaluated? measurement

Assay resolution limit

Record whether an assay establishes sample-level reactivity, a modified protein, or a particular residue; these evidence levels are not interchangeable.

1. What does the reagent detect, and which unmodified or alternatively modified controls establish its specificity? measurement
2. Would a matched synthetic peptide or an independent detection method resolve the remaining assignment ambiguity? action

Quantitative denominator

Site occupancy requires a justified estimate of the relevant substrate population; modified-peptide intensity alone should be recorded as signal rather than occupancy.

1. Is the reported quantity site occupancy, modified-peptide abundance, total citrulline signal, or reaction rate? definition
2. How are substrate abundance, recovery, response differences, and undetected values handled? measurement

Conversion timing control

Collection, storage, lysis, incubation, and quenching must be documented when the timing of conversion matters.

1. What interval and conditions separated collection from effective reaction quenching? provenance
2. Which immediate-quench or handling-time control would test whether conversion occurred after collection? action

Effect attribution

Record the measured effect and the comparison that supports attribution to citrullination, including other modifications or experimental differences that remain confounded.

1. What change in binding, activity, structure, proteolysis, or recognition was measured for the specified modified substrate? measurement
2. Does the comparison isolate citrullination at this site, or could other sites and treatment effects explain the result? boundary

Process change versus phenotype

An intervention should establish its effect on citrullination separately from downstream outcomes; a phenotypic response alone does not demonstrate modification-dependent causality.

1. Which direct modification readout will verify that the perturbation changed citrullination? action
2. What complementary perturbation or rescue could distinguish citrullination-dependent effects from off-target or substrate-abundance effects? action

Check these first

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these check these first hold for the sense of citrullination this model covers, and on what evidence? provenance

Kinds and varieties

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these kinds and varieties hold for the sense of citrullination this model covers, and on what evidence? provenance

Real-world use

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these real-world use hold for the sense of citrullination this model covers, and on what evidence? provenance

Typical measurements

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these typical measurements hold for the sense of citrullination this model covers, and on what evidence? provenance

Failure modes and hazards

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these failure modes and hazards hold for the sense of citrullination this model covers, and on what evidence? provenance

Neighbouring kinds and how to tell them apart

Recalled without web access and unsourced; every item is a lead to verify.

1. Which of these neighbouring kinds and how to tell them apart hold for the sense of citrullination this model covers, and on what evidence? provenance