Toolkit/TRIM21 RING domain

TRIM21 RING domain

Protein Domain·Research·Since 2020

Taxonomy: Mechanism Branch / Component. Workflows sit above the mechanism and technique branches rather than replacing them.

Summary

The TRIM21 RING domain is a catalytic protein domain whose ubiquitination activity is activated by substrate-induced clustering that promotes intermolecular RING dimerization. In the cited 2020 study, this activation mechanism underlies TRIM21-dependent antiviral responses and Trim-Away-mediated protein degradation.

Usefulness & Problems

Why this is useful

This domain is useful as a regulated ubiquitination module for targeted degradation contexts in which clustering can be coupled to substrate recognition. The cited work specifically links its activation logic to antiviral defense and to Trim-Away applications for degrading proteins and pathogens.

Source:

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.

Source:

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.

Problem solved

It addresses the problem of how TRIM21 ubiquitination activity is switched on in cells rather than remaining constitutively active. The study further indicates that understanding this activation mechanism is relevant to targeted protein degradation technologies.

Source:

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.

Problem links

Need conditional protein clearance

Derived

The TRIM21 RING domain is a catalytic module whose ubiquitination activity is activated by substrate-induced clustering that drives intermolecular RING dimerization. In the cited work, this mechanism underlies TRIM21-dependent antiviral responses and Trim-Away-based protein degradation.

Taxonomy & Function

Primary hierarchy

Mechanism Branch

Component: A low-level protein part used inside a larger architecture that realizes a mechanism.

Techniques

No technique tags yet.

Target processes

degradation

Implementation Constraints

cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenoperating role: actuatoroperating role: regulatorswitch architecture: multi componentswitch architecture: recruitment

The available evidence supports use cases in which substrate-induced clustering is engineered or induced to activate the TRIM21 RING domain. Domain fusion and optogenetic control are listed as known techniques, but the provided evidence does not specify construct architectures, cofactors, expression systems, or illumination parameters.

The supplied evidence is limited to a single 2020 source and does not provide quantitative performance metrics, substrate scope, or comparative benchmarking against other degradation modules. Practical constraints such as cell-type dependence, delivery format, and off-target effects are not described in the provided evidence.

Validation

Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication

Supporting Sources

Ranked Claims

Claim 1applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 2applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 3applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 4applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 5applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 6applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 7applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 8applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 9applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 10applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 11applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 12applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 13applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 14applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 15applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 16applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 17applicationsupports2020Source 1needs review

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.
Claim 18general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 19general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 20general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 21general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 22general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 23general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 24general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 25general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 26general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 27general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 28general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 29general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 30general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 31general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 32general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 33general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 34general mechanistic implicationsupports2020Source 1needs review

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.
Claim 35mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 36mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 37mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 38mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 39mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 40mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 41mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 42mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 43mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 44mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 45mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 46mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 47mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 48mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 49mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 50mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 51mechanismsupports2020Source 1needs review

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21
Claim 52tool expansionsupports2020Source 1needs review

The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Claim 53tool expansionsupports2020Source 1needs review

The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Claim 54tool expansionsupports2020Source 1needs review

The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Claim 55tool expansionsupports2020Source 1needs review

The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Claim 56tool expansionsupports2020Source 1needs review

The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Claim 57tool expansionsupports2020Source 1needs review

The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Claim 58tool expansionsupports2020Source 1needs review

The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Claim 59tool expansionsupports2020Source 1needs review

The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Claim 60tool expansionsupports2020Source 1needs review

The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.
Claim 61tool expansionsupports2020Source 1needs review

The authors expanded the Trim-Away toolbox with highly active TRIM21-nanobody chimeras that can be controlled optogenetically.

We harness this mechanism to expand the Trim-Away toolbox with highly-active TRIM21-nanobody chimeras that can also be controlled optogenetically.

Approval Evidence

1 source3 linked approval claimsfirst-pass slug trim21-ring-domain
a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21

Source:

applicationsupports

Substrate-induced clustering of TRIM21 can induce an antiviral response or drive Trim-Away.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21 and induce an antiviral response or drive Trim-Away.

Source:

general mechanistic implicationsupports

This work provides a mechanism for cellular activation of TRIM RING ligases and has implications for targeted protein degradation technologies.

This work provides a mechanism for cellular activation of TRIM RING ligases and has important implications for targeted protein degradation technologies.

Source:

mechanismsupports

Substrate-induced clustering triggers intermolecular dimerization of the TRIM21 RING domain and activates TRIM21 ubiquitination activity.

Here we show that a mechanism of substrate-induced clustering triggers intermolecular dimerization of the RING domain to switch on the ubiquitination activity of TRIM21

Source:

Comparisons

Source-backed strengths

The key strength supported by the evidence is a defined activation mechanism: substrate-induced clustering drives intermolecular dimerization of the TRIM21 RING domain and thereby activates ubiquitination. The same study connects this mechanism to functional outcomes in both antiviral response and Trim-Away.

Compared with blue light-inducible degradation (B-LID) domain

TRIM21 RING domain and blue light-inducible degradation (B-LID) domain address a similar problem space because they share degradation.

Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation

Strengths here: looks easier to implement in practice.

Compared with LOV2 domain-based optogenetic tool

TRIM21 RING domain and LOV2 domain-based optogenetic tool address a similar problem space because they share degradation.

Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation

Strengths here: looks easier to implement in practice.

Compared with photosensitive degron

TRIM21 RING domain and photosensitive degron address a similar problem space because they share degradation.

Shared frame: same top-level item type; shared target processes: degradation; shared mechanisms: degradation

Relative tradeoffs: appears more independently replicated.

Ranked Citations

  1. 1.
    StructuralSource 12020Claim 17Claim 2Claim 16

    Extracted from this source document.