Constitutively upstream of

Overview and Scope of Use

• This relation is intended to represent that an upstream activity can be REQUIRED FOR a downstream activity, but does not regulate the downstream activity. An example is that a palmitoyltransferase activity is necessary to create a mature, functional Ras protein, but the palmitoyltransferase is not used as a mechanism for regulating Ras 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 is occurring constantly and should not be considered to be 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 MF to the downstream MF 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

• Standard Annotation: This relation should not be used for conventional annotation

• GO-CAM
  • Guidelines
    • What to capture
      • Upstream activities that are required for downstream activities but are not regulatory. Examples of this would be enzymes that are needed for processing or maturation of a downstream enzyme or receptor, but are not considered to regulate the enzyme or receptor and are considered to be 'housekeeping' functions. These constitutive effects can potentially be dysregulated 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.
  • Examples
    • Zdhhc9 post-translationally modifies Nras with a palmitoyl group, resulting in its membrane association. The membrane association of an oncogenic form of NRAS that has low GTPase activity is required for its oncogenic (signaling) activity. Inhibiting the activity of Zdhhc9 decreases palmitoylation and the biological activity of oncogenic Nras. Link to reference
      • constitutively upstream of example

Quality Control Checks

• Annotations can be validated using a Shape Expressions (ShEx) representation of allowed relations between ontology terms.

Relations Ontology

constitutively upstream of

Review Status

Last reviewed: February 6, 2023

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