Background: | 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, regardeless 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. |
Synonyms: | E3 ubiquitin-protein ligase TRIP12 (EC 2.3.2.26) (E3 ubiquitin-protein ligase for Arf) (ULF) (HECT-type E3 ubiquitin transferase TRIP12) (Thyroid receptor-interacting protein 12) (TR-interacting protein 12) (TRIP-12), TRIP12, KIAA0045 ULF |
UniProt Protein Function: | 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, regardeless 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. 4 isoforms of the human protein are produced by alternative splicing. |
UniProt Protein Details: | Protein type:Ubiquitin ligase; Ligase; EC 6.3.2.-; Nuclear receptor co-regulator; Ubiquitin conjugating system; EC 6.3.2.19 Chromosomal Location of Human Ortholog: 2q36.3 Cellular Component: nucleoplasm; nucleus Molecular Function:ligase activity; protein binding; thyroid hormone receptor binding; ubiquitin-protein ligase activity Biological Process: DNA repair; embryonic development; protein ubiquitination during ubiquitin-dependent protein catabolic process; response to DNA damage stimulus |
UniProt Code: | Q14669 |
NCBI GenInfo Identifier: | 2499839 |
NCBI Gene ID: | 9320 |
NCBI Accession: | Q14669.1 |
UniProt Secondary Accession: | Q14669,Q14CA3, Q14CF1, Q15644, Q53R87, Q53TE7, D4HL82 |
UniProt Related Accession: | Q14669 |
Molecular Weight: | 192,075 Da |
NCBI Full Name: | E3 ubiquitin-protein ligase TRIP12 |
NCBI Synonym Full Names: | thyroid hormone receptor interactor 12 |
NCBI Official Symbol: | TRIP12 |
NCBI Official Synonym Symbols: | ULF; TRIP-12 |
NCBI Protein Information: | E3 ubiquitin-protein ligase TRIP12 |
UniProt Protein Name: | E3 ubiquitin-protein ligase TRIP12 |
UniProt Synonym Protein Names: | E3 ubiquitin-protein ligase for Arf; ULF; Thyroid receptor-interacting protein 12; TR-interacting protein 12; TRIP-12 |
Protein Family: | E3 ubiquitin-protein ligase |
UniProt Gene Name: | TRIP12 |
UniProt Entry Name: | TRIPC_HUMAN |