Directly 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 upstream activity has a negative (decreasing or inhibiting) effect on the immediately downstream activity. Immediately means there is no intervening activity. The mechanism by which the upstream activity controls the downstream activity must be known. The regulation commonly involves direct physical interaction between the two enablers, but may also occur when the upstream activity produces or degrades a small molecule regulator of the downstream activity.
  • The 'directly negatively regulates' relation is used to relate two GO molecular functions when:
    • Two activities act in direct succession (i.e. there is no intervening activity)
    • The upstream activity can exert its regulation on the downstream activity by, for example, a direct effect on the enabler of the downstream activity (e.g. a phosphatase) or by removal of an activator of the downstream activity (e.g. acetylcholinesterase).
    • The direct effect on the enabler reduces its ability to execute its function.

Annotation Usage Guidelines

  • What to capture
    • Upstream activities that control the activity of a downstream activity.
  • What not to capture
    • Activities that are constitutively occurring upstream of a downstream activity.


REG3A, induced by IL-33, inhibits TLR3-mediated inflammation in skin wounds. The mechanism for REG3A-inhibited inflammatory response involves induction of the negative regulatory factor SHP-1 (PTPN6), which exhibits a major role in delayed wound healing by inhibiting TLR3-activated JNK2 (MAPK9) phosphorylation. PMID:27830702

Directly negatively regulates

GO-CAM model

Ontology Usage Guidelines

This relation is used in the ontology in the logical definitions of 'molecular function inhibitor activity'.

Cross Reference to the Relation Ontology (RO)

directly negatively regulates

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