MCTS1
Domain
The PUA RNA-binding domain is critical for cap binding, but not sufficient for translation enhancer function. MCT1 N-terminal region is required to enhance translation possibly through interaction with other proteins.
Function
Translation regulator forming a complex with DENR to promote translation reinitiation. Translation reinitiation is the process where the small ribosomal subunit remains attached to the mRNA following termination of translation of a regulatory upstream ORF (uORF), and resume scanning on the same mRNA molecule to initiate translation of a downstream ORF, usually the main ORF (mORF). The MCTS1/DENR complex is pivotal to two linked mechanisms essential for translation reinitiation. Firstly, the dissociation of deacylated tRNAs from post-termination 40S ribosomal complexes during ribosome recycling. Secondly, the recruitment in an EIF2-independent manner of aminoacylated initiator tRNA to P site of 40S ribosomes for a new round of translation (PubMed:16982740, PubMed:20713520, PubMed:37875108). This regulatory mechanism governs the translation of more than 150 genes which translation reinitiation is MCTS1/DENR complex-dependent (PubMed:16982740, PubMed:20713520, PubMed:37875108). Consequently, modulates various unrelated biological processes including cell cycle regulation and DNA damage signaling and repair (PubMed:10440924, PubMed:11709712, PubMed:12637315, PubMed:15897892, PubMed:16322206, PubMed:17016429, PubMed:17416211, PubMed:9766643). Notably, it positively regulates interferon gamma immunity to mycobacteria by enhancing the translation of JAK2 (PubMed:37875108).
Involvement in disease
Immunodeficiency 118
IMD118
An X-linked recessive disorder characterized by increased susceptibility to disseminated mycobacterial infections in infancy, notably after Bacillus Calmette-Guerin (BCG) vaccination. Initial clinical features include fever, lymphadenopathy, hepatosplenomegaly, abscesses, and osteomyelitis. Affected males usually recover with treatment, have no other infections, and show normal growth and development.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation is critical for stabilization and promotion of cell proliferation.
Sequence Similarities
Belongs to the MCTS1 family.
Tissue Specificity
Ubiquitous. Over-expressed in T-cell lymphoid cell lines and in non-Hodgkin lymphoma cell lines as well as in a subset of primary large B-cell lymphomas.
Cellular localization
- Cytoplasm
- Nuclear relocalization after DNA damage.
Alternative names
MCT1, MCTS1, Malignant T-cell-amplified sequence 1, MCT-1, Multiple copies T-cell malignancies