PROSITE documentation PDOC51886
TLDc domain profile


The Tre2/Bub2/Cdc16 (TBC), lysin motif (LysM), domain catalytic (TLDc) domain is present in all eukaryotes, and its primary sequence is highly conserved among species. The TLDc domain is present in several proteins that share a protective function against oxidative stress (OS):

  • nuclear receptor coactivator 7 (NCOA7 or TLDC4), a nuclear receptor coregulator modulating gene transcription.
  • oxidation resistance 1 (OXR1 or TLDC3), regulates expression of enzymes that detoxify reactive oxygen species (ROS).
  • TBC1 domain family member 24 (TBC1D24 or TLDC6), involved in neuronal projections development, probably through a negative modulation of ARF6 function.
  • TBC/LysM-associated domain containing 1 (KIAA1609 or TLDC1).
  • TBC/LysM-associated domain containing 2 (C200ORF118 or TLDC2).
  • interferon-induced protein 44 (IFI44 or TLDC5).

The TLDc domain alone is able to confer oxidative resistance properties to all the TLDc members. The TLDc domain-containing proteins could influence the expression of key oxygen free-radical scavengers that, in turn, reduce the levels of ROS in the cell [1,2,3,4].

The TLDc domain is a conserved protein motif of ~200 amino acids whose overall structure is globular. Two antiparallel β-sheets form a central β-sandwich, surrounded by two helices and two one-turn helices (see <PDB:4ACJ>). Each β-sheet is composed of six and four strands. The two sheets organize as a pseudo-orthogonal β-sandwich and interact with each other only by hydrophobic interactions [4].

The profile we developed covers the entire TLDc domain.

Last update:

March 2019 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

TLDC, PS51886; TLDc domain profile  (MATRIX)


1AuthorsFinelli M.J. Oliver P.L.
TitleTLDc proteins: new players in the oxidative stress response and neurological disease.
SourceMamm. Genome 28:395-406(2017).
PubMed ID28707022

2AuthorsFinelli M.J. Sanchez-Pulido L. Liu K.X. Davies K.E. Oliver P.L.
TitleThe Evolutionarily Conserved Tre2/Bub2/Cdc16 (TBC), Lysin Motif (LysM), Domain Catalytic (TLDc) Domain Is Neuroprotective against Oxidative Stress.
SourceJ. Biol. Chem. 291:2751-2763(2016).
PubMed ID26668325

3AuthorsJaramillo-Gutierrez G. Molina-Cruz A. Kumar S. Barillas-Mury C.
TitleThe Anopheles gambiae oxidation resistance 1 (OXR1) gene regulates expression of enzymes that detoxify reactive oxygen species.
SourcePLoS One. 5:E11168-E11168(2010).
PubMed ID20567517

4AuthorsBlaise M. Alsarraf H.M.A.B. Wong J.E.M.M.. Midtgaard S.R. Laroche F. Schack L. Spaink H. Stougaard J. Thirup S.
TitleCrystal structure of the TLDc domain of oxidation resistance protein 2 from zebrafish.
SourceProteins 80:1694-1698(2012).
PubMed ID22434723

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