TRIM27

Description

The TRIM27 (tripartite motif containing 27) is a protein-coding gene located on chromosome 6.

TRIM27 is a protein encoded by the TRIM27 gene in humans. It belongs to the tripartite motif (TRIM) family, characterized by three zinc-binding domains: a RING, a B-box type 1, and a B-box type 2, along with a coiled-coil region. This protein localizes to the nuclear matrix, interacts with the enhancer of polycomb protein, and represses gene transcription. It is also believed to be involved in the differentiation of male germ cells. Fusion of the N-terminus of TRIM27 with the truncated C-terminus of the RET gene product results in the production of the ret transforming protein. TRIM27 interacts with PRAM1 and EIF3S6.

TRIM27 is an E3 ubiquitin-protein ligase that mediates ubiquitination of various substrates, playing a role in processes like proliferation, innate immunity, apoptosis, immune response, and autophagy. It ubiquitinates PIK3C2B and inhibits its activity by mediating the formation of 'Lys-48'-linked polyubiquitin chains, which inhibits CD4 T-cell activation. Along with MAGEL2, it regulates retrograde transport by forming 'Lys-63'-linked polyubiquitin chains at 'Lys-220' of WASHC1, promoting endosomal F-actin assembly. TRIM27 functions as a transcriptional repressor by cooperating with EPC1. It induces apoptosis by activating Jun N-terminal kinase and p38 kinase, increasing caspase-3-like activity independently of mitochondrial events. It may play a role in male germ cell development. TRIM27 binds to double-stranded DNA and forms a complex with and ubiquitinates the ubiquitin-specific protease USP7. This deubiquitinates RIPK1, positively regulating TNF-alpha-induced apoptosis. TRIM27 acts with USP7 or PTPN11 as an inhibitor of the antiviral signaling pathway, promoting kinase TBK1 ubiquitination and degradation. It negatively regulates NOD2 signaling by ubiquitinating NOD2, promoting its degradation by the proteasome. Alternatively, it facilitates mitophagy through stabilization of active TBK1. Under basal conditions, TRIM27 negatively regulates autophagy flux by directly polyubiquitinating ULK1. During starvation-induced autophagy, it catalyzes non-degradative ubiquitination of the kinase STK38L, promoting its activation and phosphorylation of ULK1. This leads to ULK1 ubiquitination and degradation, restraining the amplitude and duration of autophagy. It positively regulates hepatitis C virus replication by suppressing type I IFN response during infection. TRIM27 forms homomultimers and is part of a complex with USP7 and MAGEL2. It directly interacts with USP7, PML, EIF3S6, EPC1, CHD4, EID1, MAGED4, MAGEF1, MAGEL2, PTPN11, autophagy receptor p62/SQSTM1, M.tuberculosis PtpA, and herpes simplex virus protein ICP0.

TRIM27 is also known as RFP, RNF76.

Associated Diseases

WES Whole Exome Sequencing