{PDOC51886} {PS51886; TLDC} {BEGIN} *********************** * 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 beta-sheets form a central beta- sandwich, surrounded by two helices and two one-turn helices (see ). Each beta-sheet is composed of six and four strands. The two sheets organize as a pseudo-orthogonal beta-sandwich and interact with each other only by hydrophobic interactions [4]. The profile we developed covers the entire TLDc domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: March 2019 / First entry. [ 1] Finelli M.J., Oliver P.L. "TLDc proteins: new players in the oxidative stress response and neurological disease." Mamm. Genome 28:395-406(2017). PubMed=28707022; DOI=10.1007/s00335-017-9706-7 [ 2] Finelli M.J., Sanchez-Pulido L., Liu K.X., Davies K.E., Oliver P.L. "The Evolutionarily Conserved Tre2/Bub2/Cdc16 (TBC), Lysin Motif (LysM), Domain Catalytic (TLDc) Domain Is Neuroprotective against Oxidative Stress." J. Biol. Chem. 291:2751-2763(2016). PubMed=26668325; DOI=10.1074/jbc.M115.685222 [ 3] Jaramillo-Gutierrez G., Molina-Cruz A., Kumar S., Barillas-Mury C. "The Anopheles gambiae oxidation resistance 1 (OXR1) gene regulates expression of enzymes that detoxify reactive oxygen species." PLoS One. 5:E11168-E11168(2010). PubMed=20567517; DOI=10.1371/journal.pone.0011168 [ 4] Blaise M., Alsarraf H.M.A.B., Wong J.E.M.M.., Midtgaard S.R., Laroche F., Schack L., Spaink H., Stougaard J., Thirup S. "Crystal structure of the TLDc domain of oxidation resistance protein 2 from zebrafish." Proteins 80:1694-1698(2012). PubMed=22434723; DOI=10.1002/prot.24050 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}