TRIP4
Domain
The C4-type zinc finger mediates a competitive interaction with UFSP2 and ligand-bound nuclear receptors. It also mediates interaction with the transcriptional coactivators and the basal transcription machinery.
Function
Transcription coactivator which associates with nuclear receptors, transcriptional coactivators including EP300, CREBBP and NCOA1, and basal transcription factors like TBP and TFIIA to facilitate nuclear receptors-mediated transcription (PubMed:10454579, PubMed:25219498). May thereby play an important role in establishing distinct coactivator complexes under different cellular conditions (PubMed:10454579, PubMed:25219498). Plays a role in thyroid hormone receptor and estrogen receptor transactivation (PubMed:10454579, PubMed:25219498). Also involved in androgen receptor transactivation (By similarity). Plays a pivotal role in the transactivation of NF-kappa-B, SRF and AP1 (PubMed:12077347). Acts as a mediator of transrepression between nuclear receptor and either AP1 or NF-kappa-B (PubMed:12077347). May play a role in the development of neuromuscular junction (PubMed:26924529). May play a role in late myogenic differentiation (By similarity). Also functions as part of the RQC trigger (RQT) complex that activates the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation (PubMed:32099016, PubMed:32579943, PubMed:36302773).
Involvement in disease
Spinal muscular atrophy with congenital bone fractures 1
SMABF1
An autosomal recessive neuromuscular disorder characterized by prenatal-onset spinal muscular atrophy, multiple congenital contractures consistent with arthrogryposis multiplex congenita, respiratory distress, and congenital bone fractures.
None
The disease is caused by variants affecting the gene represented in this entry.
Muscular dystrophy, congenital, Davignon-Chauveau type
MDCDC
An autosomal recessive, severe congenital muscular dystrophy characterized by neonatal onset of muscle weakness predominantly involving axial muscles, life-threatening respiratory failure, skin abnormalities and joint hyperlaxity without contractures. Muscle biopsies show multi-minicores, caps and dystrophic lesions.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated by NEK6.
Polyufmylated by the UFM1-conjugating system composed of the enzymes UBA5, UFC1 and UFL1. Deufmylated by the protease UFSP2. Ufmylation of TRIP4 is promoted by ligand-bound nuclear receptors that compete with UFSP2 for interaction with TRIP4. Nuclear receptors-induced ufmylation promotes the recruitment of additional transcriptional coactivators like EP300 and NCOA1 and therefore the assembly of a coactivator complex facilitating nuclear receptor-mediated transcription.
Cellular localization
- Nucleus
- Cytoplasm
- Cytosol
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Cytoplasmic under conditions of serum deprivation (PubMed:10454579). Colocalizes with NEK6 in the centrosome (PubMed:20873783).
Alternative names
RQT4, TRIP4, Activating signal cointegrator 1, ASC-1, Thyroid receptor-interacting protein 4, TR-interacting protein 4, TRIP-4