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 human Ortholog: 2q36.3
Cellular Component:  cytosol; nuclear speck; nucleoplasm
Molecular Function:  nuclear thyroid hormone receptor binding; protein binding; ubiquitin protein ligase activity
Biological Process:  cellular response to DNA damage stimulus; DNA repair; negative regulation of double-strand break repair; negative regulation of histone H2A K63-linked ubiquitination; proteasome-mediated ubiquitin-dependent protein catabolic process; protein polyubiquitination; regulation of double-strand break repair; regulation of embryonic development; ubiquitin-dependent protein catabolic process
Disease: Mental Retardation, Autosomal Dominant 49
Reference #:  Q14669 (UniProtKB)
Alt. Names/Synonyms: E3 ubiquitin-protein ligase for Arf; E3 ubiquitin-protein ligase TRIP12; HECT-type E3 ubiquitin transferase TRIP12; KIAA0045; MGC138849; MGC138850; MRD49; Probable E3 ubiquitin-protein ligase TRIP12; thyroid hormone receptor interactor 12; thyroid receptor interacting protein 12; Thyroid receptor-interacting protein 12; TR-interacting protein 12; TRIP-12; TRIP12; TRIPC; ULF
Gene Symbols: TRIP12
Molecular weight: 220,434 Da
Basal Isoelectric point: 8.76  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  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene  |  NURSA