Indirectly positively 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 positive 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 transcription factor activity to the activity of the product of the transcribed gene. The mechanism is known (transcription and translation) 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 a regulation biological process term (e.g. regulation of transcription has_input target gene) to capture which process is left out of the model.
  • The 'indirectly positively 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 increases execution of the downstream activity (positive)
    • Execution of the upstream activity is conditional (regulation)

Annotation Usage Guidelines

  • What to capture
    • This relation is typically used for activities that are part of activity-regulating BPs, e.g. regulation of gene expression and its children, that increase expression and thus, activity, of the downstream target.
  • What to capture
    • Indirectness indicates that there are intervening activities, e.g. general transcription factor activities, 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 DAF-16 is required for transcription of the cyclin-dependent kinase inhibitor cki-1 in stem cells in response to starvation. In starved daf-16(mgDf50) L1 larvae, physiologically regulated cki-1::GFP expression is absent or diminished in V lineage seam cells, indicating that DAF-16 is required for physiologically regulated expression of cki-1::GFP. In the corresponding GO-CAM model of negative regulation of nematode larval development in response to starvation, DAF-16 thus indirectly positively regulates the cyclin-dependent serine/threonine kinase inhibitor activity of CKI-1.

Indirectly positively regulates GO-CAM example

GO-CAM model

Relations Ontology

indirectly positively 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

Back to: Annotation Relations