TRIP12 — Thyroid hormone receptor interactor 12
TRIP12 belongs to a gene co-expression module in 4 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
TRIP12's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD4⁺ T cells | Actomyosin signaling migration & adhesion | ACIN1, CYBC1, EIF4G3, GALNT1, HNRNPA3, NCKAP1L, PPP1R12A, PRKCH +8 more | View in SCUBA |
| Gamma-delta T cells | DNA Damage Response DNA/chromatin regulation | AP1B1, CCAR1, CHD8, DOCK2, EP400, ERBIN, GOLM2, IPO8 +17 more | |
| Macrophages | Chromatin Regulatory Genes Housekeeping | ACAP2, ARID4A, ATRX, BPTF, BRD10, BRD4, EP300, ERBIN +31 more | View in SCUBA |
| Mucosal-associated invariant T cell | Immune Synapse Signaling TCR Signaling | APC, ARHGAP26, ASXL2, CD46, CPSF2, DOCK8, EEA1, EIF4G3 +21 more |
About the gene
| Synonyms | KIAA0045, TRIPC, ULF |
|---|---|
| Chromosome | 2: 229763837-229923239 |
| Predicted location | Intracellular |
| Essential gene | No |
| Protein class | Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins |
| Molecular function | Transferase |
| Biological process | DNA damage, DNA repair, Ubl conjugation pathway |
Function
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. 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. 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. Mediates ubiquitination of ASXL1: following binding to N(6)-methyladenosine methylated DNA, ASXL1 is ubiquitinated by TRIP12, leading to its degradation and subsequent inactivation of the PR-DUB complex.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.