TRIP4

TRIP4 is a subunit of the tetrameric nuclear activating signal cointegrator 1 (ASC-1) complex, which associates with transcriptional coactivators, nuclear receptors and basal transcription factors to facilitate nuclear receptors-mediated transcription. Th

Full Name

Thyroid Hormone Receptor Interactor 4

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. May thereby play an important role in establishing distinct coactivator complexes under different cellular conditions. 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. 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).

Biological Process

Biological Process intracellular estrogen receptor signaling pathway Source:UniProtKB1 Publication
Biological Process positive regulation of DNA-templated transcription Source:UniProtKB1 Publication
Biological Process regulation of DNA-templated transcription Source:UniProtKB1 Publication
Biological Process regulation of myoblast differentiation Source:UniProtKB
Biological Process rescue of stalled ribosome Source:UniProtKB1 Publication
Biological Process ribosome disassembly Source:ComplexPortal1 Publication
Biological Process ribosome-associated ubiquitin-dependent protein catabolic process Source:UniProtKB1 Publication
Biological Process toxin transport Source:Ensembl

Cellular Location

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).

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.
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.

PTM

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.