TRIP12 E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins. In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor required for p53/TP53 activation under oncogenic stress. In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation. Does not mediate ubiquitination of isoform p16-INK4a of CDKN2A. Also catalyzes ubiquitination of NAE1 and SMARCE1, leading to their degradation. Ubiquitination and degradation of target proteins is regulated by interaction with proteins such as MYC, TRADD or SMARCC1, which disrupt the interaction between TRIP12 and target proteins. Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes. Belongs to the UPL family. K-HECT subfamily. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 6.3.2.-; EC; Ligase; Nuclear receptor co-regulator; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of mouse Ortholog: 1|1 C5
Cellular Component:  nuclear speck; nucleoplasm; nucleus
Molecular Function:  nuclear thyroid hormone receptor binding; transferase activity; ubiquitin protein ligase activity; ubiquitin-protein transferase activity; zinc ion binding
Biological Process:  DNA damage response; DNA repair; DNA repair-dependent chromatin remodeling; heterochromatin boundary formation; proteasome-mediated ubiquitin-dependent protein catabolic process; protein polyubiquitination; regulation of embryonic development; ubiquitin-dependent protein catabolic process
Reference #:  G5E870 (UniProtKB)
Alt. Names/Synonyms: 1110036I07Rik; 6720416K24Rik; AA410158; E3 ubiquitin-protein ligase TRIP12; gene trap locus 6; Gtl; Gtl6; HECT-type E3 ubiquitin transferase TRIP12; MGC31615; thyroid hormone receptor interactor 12; thyroid receptor interactor TRIP12; Thyroid receptor-interacting protein 12; TR-interacting protein 12; TRIP-12; Trip12; Trip12 protein; TRIPC
Gene Symbols: Trip12
Molecular weight: 224,128 Da
Basal Isoelectric point: 8.64  Predict pI for various phosphorylation states
CST Pathways:  G2/M DNA Damage Checkpoint
Select Structure to View Below


Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  NURSA  |  Ensembl Protein