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THEMIS: new insights into its evolution, structure, and function.

Avik Dutta1, L Aravind2, Seeyoung Choi1

  • 1Section on Hematopoiesis and Lymphocyte Biology, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

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|April 2, 2026
PubMed
Summary
This summary is machine-generated.

THEMIS, a molecule crucial for T cell receptor signaling, has a controversial molecular function. This review clarifies its mechanism in T cell development and mature T cells, focusing on the CABIT module.

Keywords:
CABITT cell activationT cell developmentTCRTHEMISsignal transduction

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Area of Science:

  • Immunology
  • Molecular Biology
  • Protein Structure

Background:

  • THEMIS (thymocyte-expressed molecule involved in selection) is key in T cell receptor (TCR) signaling during development and in peripheral T cells.
  • The precise molecular function of THEMIS in TCR signaling has been debated due to conflicting experimental findings.
  • THEMIS proteins contain a unique structural element, the cysteine-containing all-beta-in-THEMIS (CABIT) module.

Purpose of the Study:

  • To review recent data on the structure, evolution, and functions of the CABIT module.
  • To elucidate the molecular mechanism by which THEMIS impacts TCR and cytokine receptor signaling.
  • To resolve controversies surrounding THEMIS's role in T cell signaling.

Main Methods:

  • Literature review of recent experimental data.
  • Analysis of structural and evolutionary aspects of the CABIT module.
  • Synthesis of findings to clarify THEMIS's molecular function.

Main Results:

  • THEMIS plays a critical role in both T cell development and peripheral T cell function.
  • The CABIT module is a defining feature of THEMIS family proteins.
  • Recent data clarify THEMIS's mechanism in modulating TCR and cytokine receptor signaling pathways.

Conclusions:

  • This review consolidates current knowledge, offering new insights into THEMIS structure, evolution, and function.
  • The molecular mechanism of THEMIS in T cell signaling is clarified, resolving previous controversies.
  • THEMIS is essential for proper T cell function throughout their lifespan.