RFFL

RFFL (Ring Finger And FYVE Like Domain Containing E3 Ubiquitin Protein Ligase) is a Protein Coding gene. Among its related pathways are Gene Expression and Regulation of TP53 Activity. Gene Ontology (GO) annotations related to this gene include protein kinase binding and ubiquitin protein ligase binding. An important paralog of this gene is RNF34.

Full Name

ring finger and FYVE-like domain containing 1

Function

E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling.

Biological Process

Biological Process apoptotic processIEA:UniProtKB-KW
Biological Process negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of extrinsic apoptotic signaling pathway via death domain receptorsManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of signal transduction by p53 class mediatorManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of tumor necrosis factor-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process proteasome-mediated ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein K48-linked ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of fibroblast migrationISS:UniProtKB
Biological Process regulation of signal transduction by p53 class mediatorTAS:Reactome
Biological Process regulation of TOR signaling1 PublicationIC:UniProtKB
Biological Process ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB

Cellular Location

Cytoplasm, cytosol
Cell membrane
Recycling endosome membrane
The FYVE-type zinc finger may mediate phosphatidylinositol phosphate-binding and control subcellular localization.

PTM

Autoubiquitinated.
Palmitoylated.
Undergoes caspase-mediated cleavage upon death-receptor activation, by TNFSF10 for instance. May be mediated by the caspases CASP8 and CASP10 in a negative feedback loop.