Indirectly negatively regulates

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Overview and Scope of Use

  • This relation is used in GO-CAMs but not in standard annotation extensions.
  • This relation links two activities when the first activity has a negative regulatory effect on the second activity via a larger process (module) that is reused in many contexts. In this case, curators are not required to model the larger process (module) in every GO-CAM that refers to it. Examples include linking a ubiquitin protein ligase activity to the activity of the protein that is ubiquitinated and degraded. The mechanism is known (in this case, proteasome-mediated protein degradation) but the process is not specific to this context, and would not be included in the model. In this case, the curator should also include a part_of link from the upstream activity to a regulation biological process term (e.g. regulation of proteasome-mediated protein catabolic process has_input target protein) to capture which larger process is left out of the model.
  • The 'indirectly negatively regulates' relation is used to relate two GO molecular functions when:
    • The upstream activity occurs before the downstream activity, but there are intervening activities between them (indirect)
    • The mechanism that relates the upstream activity to the downstream activity is understood
    • The upstream activity decreases execution of the downstream activity (negative)
    • Execution of the upstream activity is conditional (regulation)

Annotation Usage Guidelines

  • What to capture
    • This relation is typically used with upstream activities that are part of activity-regulating biological processes, e.g. negative regulation of gene expression and its children, that reduce expression and thus activity of the downstream target.
  • What not to capture
    • Indirectness indicates that there are intervening activities, e.g. general transcription factor activities or endoribonucleases, between the two activities connected with this relation. Since the intervening activities may be part of a larger coordinated process of gene expression, it is not necessary for curators to model the entire coordinated process in their GO-CAM.


C. elegans msi-1 encodes a member of the Musashi family of RNA-binding proteins that, in response to signaling via an AMPA-type glutamate receptor, binds to mRNA 3'UTRs encoding members of the Arp2/3 complex to repress their translation and alter actin cytoskeleton organization in the context of regulation of memory loss. In a GO-CAM, this indirect regulation is modeled as: mRNA base-pairing translational repressor activity enabled by MSI-1 indirectly negatively regulates actin binding activity enabled by ARX-2. PMID:24630719

Indirectly negatively regulates GO-CAM example

Relations Ontology

indirectly negatively regulates

Review Status

Last reviewed: February 15, 2023

Reviewed by: Cristina Casals, Marc Feuermann, Pascale Gaudet, David Hill, Patrick Masson, Sylvain Poux, Paul Thomas, Kimberly Van Auken

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