InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TRIP12

Summary

InnateDB Protein

IDBP-82751.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TRIP12

Protein Name

thyroid hormone receptor interactor 12

Synonyms

TRIP-12; ULF;

Species

Homo sapiens

Ensembl Protein

ENSP00000283943

InnateDB Gene

IDBG-82749 (TRIP12)

Protein Structure

UniProt Annotation

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, 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. {ECO:0000269PubMed:18627766, ECO:0000269PubMed:19028681, ECO:0000269PubMed:20208519, ECO:0000269PubMed:20829358, ECO:0000269PubMed:22884692}.

Subcellular Localization

Nucleus, nucleoplasm {ECO:0000269PubMed:20208519}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 39 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	39 [view]
Protein-Protein	39 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005488	binding
GO:0005515	protein binding
GO:0016874	ligase activity
GO:0046966	thyroid hormone receptor binding

Biological Process

GO:0006281	DNA repair
GO:0006974	cellular response to DNA damage stimulus
GO:0009790	embryo development
GO:0042787	protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:1901315	negative regulation of histone H2A K63-linked ubiquitination
GO:2000780	negative regulation of double-strand break repair