TRIP1-TRIP15 genes encode thyroid hormone receptor β (TR β)-binding proteins. TRIP15, along with Cops2 and Alien comprise the second subunit (CSN2) of the COP9 signalosome (CSN), an eight-subunit complex with a variety of functions. CSN regulates Skp1-cullin-F-box protein (SCF) ubiquiting ligases by deconjugating Nedd8 from the Cul1 component of the SCF, and also associates with protein kinase activities targetting p53, c-Jun, and IκB. Consequently, inhibition of SCF ubiquitin ligase activity occurs, and cell cycle progression halts at the transition from G1 to S phase. TRIP15 contains an acidic region in the N terminus, a putative zinc finger in the C terminus, and a central hydrophobic core region flanked by 2 putative α-helical structures and a nuclear localization signal.
Function:
Essential component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8/ICSBP, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Involved in early stage of neuronal differentiation via its interaction with NIF3L1.
Subunit:
Interacts with NIF3L1 (By similarity). Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COP6, COPS7 (COPS7A or COPS7B) and COPS8. In the complex, it probably interacts directly with COPS1, COPS4, COPS5 COPS6 and COPS7 (COPS7A or COPS7B). Interacts with CUL1 and CUL2.Specifically interacts with the ligand binding domain of the thyroid receptor (TR). Does not require the presence of thyroid hormone for its interaction. Interacts with IRF8/ICSBP1 and with nuclear receptors NR2F1 and NR0B1.
Subcellular Location:
Cytoplasm. Nucleus.
Post-translational modifications:
Phosphorylated by CK2 and PKD kinases.
Similarity:
Belongs to the CSN2 family.
Contains 1 PCI domain.
SWISS:
P61201
Gene ID:
9318
Database links:
Entrez Gene: 430917 Chicken
Entrez Gene: 9318 Human
Entrez Gene: 12848 Mouse
Entrez Gene: 100125956 Pig
Entrez Gene: 261736 Rat
Entrez Gene: 548537 Xenopus tropicalis
Omim: 604508 Human
SwissProt: P61201 Human
SwissProt: P61202 Mouse
SwissProt: P61203 Rat
SwissProt: Q6IR75 Xenopus laevis
Unigene: 369614 Human
Unigene: 3596 Mouse
Unigene: 11556 Rat
Unigene: 83155 Xenopus laevis
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