Constitutively upstream of

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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 upstream activity is required for the downstream activity, but does not regulate the downstream activity. An example is a palmitoyltransferase activity that is necessary to create a mature, functional, lipid-modified Ras protein, yet the palmitoyltransferase activity is not used as a mechanism for regulating Ras G protein activity. The palmitoyltransferase activity is required for Ras activity, but under normal conditions (or the conditions being modeled, e.g. a particular cell type) it occurs constantly and is otherwise not regulating (controlling) Ras activity.
  • The 'constitutively upstream of' relation is used to relate two GO Molecular Functions (MF) when:
    • The mechanism that relates the upstream activity to the downstream activity is understood
    • The activities in the upstream event occur before the downstream event
    • The upstream event is required for the execution of the downstream event
    • The execution of the upstream event is approximately constant

Annotation Usage Guidelines

  • What to capture
    • Upstream activities that are required for downstream activities but are not regulatory. Examples of this would be enzymatic activities that are needed for processing or maturation of a downstream enzyme or receptor, but are not considered to regulate the enzyme or receptor activities and are considered to be 'housekeeping' functions. These constitutive effects can potentially be disrupted in disease, but are present under normal conditions.
  • What not to capture
    • This relation should not be used to capture upstream activities that occur before a downstream activity, but aren't necessary for the downstream activity to occur.


  • Zdhhc9 post-translationally modifies Nras with a palmitoyl group, resulting in its membrane association. This modification is necessary for normal Nras function. GO-CAM should model the normal process. But the model will still be helpful in interpreting perturbed processes. For example, in some cancers, an oncogenic form of NRAS that has low GTPase activity is also dependent on palmitoylation, and therefore inhibiting the activity of Zdhhc9 decreases palmitoylation and the biological activity of oncogenic Nras. PMID:26493479

Constitutively upstream GO-CAM example

GO-CAM model

Ontology Usage Guidelines

This relation is not used in the ontology.

Relations Ontology

constitutively upstream of

Review Status

Last reviewed: February 15, 2023

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

Back to: Annotation Relations