Protein: Zinc finger protein RFP (EC 2.3.2.27) (Ret finger protein) (Tripartite motif-containing protein 27) (Q62158)
Organism: Mus musculus (Mouse)
Function: E3 ubiquitin-protein ligase that mediates ubiquitination of various substrates and thereby plays a role in diffent processes including proliferation, apoptosis, immune response or autophagy. Ubiquitinates PIK3C2B and inhibits its activity by mediating the formation of 'Lys-48'-linked polyubiquitin chains; the function inhibits CD4 T-cell activation. Acts as a regulator of retrograde transport: together with MAGEL2, mediates the formation of 'Lys-63'-linked polyubiquitin chains at 'Lys-220' of WASHC1, leading to promote endosomal F-actin assembly. Has a transcriptional repressor activity by cooperating with EPC1. Induces apoptosis by activating Jun N-terminal kinase and p38 kinase and also increases caspase-3-like activity independently of mitochondrial events. May function in male germ cell development. Has DNA-binding activity and preferentially bound to double-stranded DNA. Forms a complex with and ubiquitinates the ubiquitin-specific protease USP7, which in turn deubiquitinates RIPK1 resulting in the positive regulation of TNF-alpha-induced apoptosis. In addition, acts with USP7 or PTPN11 as an inhibitor of the antiviral signaling pathway by promoting kinase TBK1 ubiquitination and degradation. Alternatively, facilitates mitophagy via TBK1 activation. Negatively regulates autophagy flux under basal conditions by directly polyubiquitinating ULK1. During starvation-induced autophagy, catalyzes non-degradative ubiquitination of the kinase STK38L promoting its activation and phosphorylation of ULK1 leading to its ubiquitination and degradation to restrain the amplitude and duration of autophagy.
Subcellular location: Nucleus {ECO:0000250|UniProtKB:P14373}. Cytoplasm {ECO:0000250|UniProtKB:P14373}. Nucleus, PML body {ECO:0000250|UniProtKB:P14373}. Early endosome {ECO:0000250|UniProtKB:P14373}. Mitochondrion {ECO:0000250|UniProtKB:P14373}. Note=Nuclear or cytoplasmic depending on the cell type (By similarity). Colocalized with PML and EIF3S6 in nuclear bodies. Recruited to retromer-containing endosomes via interaction with MAGEL2. Co-localizes with p62/SQSTM1 and TBK1 in cytoplasmic structures that are closely associated with the mitochondria (By similarity). {ECO:0000250|UniProtKB:P14373, ECO:0000269|PubMed:10571821}.
Interaction partners:
- MAGE-like protein 2
- Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
- Ubiquitin carboxyl-terminal hydrolase 7
- Sialoadhesin
- Inhibitor of nuclear factor kappa-B kinase subunit alpha
- Sorting nexin-27
- Transcription intermediary factor 1-beta
- Vacuolar protein sorting-associated protein 35
- Serine/threonine-protein kinase TBK1
- Vacuolar protein sorting-associated protein 29
Sequence:
MASGSVAECLQQETTCPVCLQYFVEPMMLDCGHNICCACLARCWGAAETNVSCPQCRETFPQRHMRPNRHLANVTQLVKQLRTERPSGPGGEMGVCEKHREPLKLYCEQDQMPICVVCDRSREHRGHSVLPLEEAVEGFKEQIQNRLDHLRRVKDLKKRRRAQGEQARAELLSLTQMEREKIVWEFEQLYHSLKEHEYRLLARLEELDLAIYNSINGAITQFSCNISHLSGLIAQLEEKQQQPTRELLQDIGDTLSRAERIRIPEPWITPPDLQEKIHIFAQKCLFLTESLKQFTEKMQSDMEKIQELREAQLYSVDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRKGGVTSAPQNGFWAVSLWYGKEYWALTSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVRPYFSLSYSGGKSAAPLIICPMSGIDGFSGHVGNHGHSMETSP