InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RFFL

Summary

InnateDB Protein

IDBP-241266.6

Last Modified

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

Gene Symbol

RFFL

Protein Name

ring finger and FYVE-like domain containing 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000378096

InnateDB Gene

IDBG-41038 (RFFL)

Protein Structure

UniProt Annotation

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. Also ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate apoptosis downstream of death domain receptors. Also 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 SNF. May also play a role in endocytic recycling. {ECO:0000269PubMed:15069192, ECO:0000269PubMed:17121812, ECO:0000269PubMed:18382127, ECO:0000269PubMed:18450452, ECO:0000269PubMed:22609986}.

Subcellular Localization

Cytoplasm, cytosol. Cell membrane; Peripheral membrane protein. Recycling endosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=The FYVE-type zinc finger may mediate phosphatidylinositol phosphate- binding and control subcellular localization.

Disease Associations

Tissue Specificity

Ubiquitous. Detected in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes. {ECO:0000269PubMed:15069192}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 18 experimentally validated interaction(s) in this database.

Experimentally validated
Total	18 [view]
Protein-Protein	18 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002020	protease binding
GO:0002039	p53 binding
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity
GO:0019901	protein kinase binding
GO:0031625	ubiquitin protein ligase binding

Biological Process

GO:0006511	ubiquitin-dependent protein catabolic process
GO:0010762	regulation of fibroblast migration
GO:0010804	negative regulation of tumor necrosis factor-mediated signaling pathway
GO:0032006	regulation of TOR signaling
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0070936	protein K48-linked ubiquitination
GO:1901797	negative regulation of signal transduction by p53 class mediator
GO:1902042	negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:2001271	negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis

Cellular Component

GO:0002947	tumor necrosis factor receptor superfamily complex
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0010008	endosome membrane
GO:0016020	membrane
GO:0055038	recycling endosome membrane