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Aliases for RFFL Gene

Aliases for RFFL Gene

  • Ring Finger And FYVE Like Domain Containing E3 Ubiquitin Protein Ligase 2 3 5
  • RING Finger And FYVE-Like Domain-Containing Protein 1 3 4
  • Caspases-8 And -10-Associated RING Finger Protein 2 3 4
  • RING-Type E3 Ubiquitin Transferase Rififylin 3 4
  • Caspase 8 And 10 Associated RING Protein-2 2 3
  • Caspase Regulator CARP2 3 4
  • RING Finger Protein 189 3 4
  • CARP-2 3 4
  • RNF189 3 4
  • RNF34L 3 4
  • FRING 3 4
  • Ring Finger And FYVE-Like Domain Containing 1 3
  • Ring Finger And FYVE-Like Domain Containing 2
  • E3 Ubiquitin-Protein Ligase Rififylin 3
  • FYVE-RING Finger Protein SAKURA 3
  • FYVE-RING Finger Protein Sakura 4
  • RING Finger Protein 34-Like 4
  • EC 2.3.2.27 4
  • RIFIFYLIN 3
  • EC 6.3.2 61
  • CARP2 3

External Ids for RFFL Gene

Previous GeneCards Identifiers for RFFL Gene

  • GC17M030360
  • GC17M033333
  • GC17M029522

Summaries for RFFL Gene

GeneCards Summary for RFFL Gene

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

UniProtKB/Swiss-Prot for RFFL Gene

  • 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.

Gene Wiki entry for RFFL Gene

No data available for Entrez Gene Summary , CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RFFL Gene

Genomics for RFFL Gene

Regulatory Elements for RFFL Gene

Enhancers for RFFL Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH17G035083 2 FANTOM5 Ensembl ENCODE dbSUPER 20.5 +2.2 2167 6.6 HDGF FOXA2 PKNOX1 MLX AGO1 WRNIP1 ARID4B SIN3A DMAP1 YY1 LIG3 RFFL SLFN5 ZNF830 CCT6B NLE1 RPL37P22
GH17G035062 1.4 ENCODE dbSUPER 15.8 +25.1 25103 3.9 PKNOX1 FOXA2 MLX ARNT WRNIP1 ARID4B SIN3A FEZF1 DMAP1 ZNF2 LIG3 RFFL LINC02001 RNU6-840P CCT6B GC17M035056 ENSG00000267457
GH17G034996 1.3 Ensembl ENCODE dbSUPER 11.6 +91.4 91372 2.6 ELF3 HDGF CTCF PKNOX1 SAP130 ARID4B RAD21 ZFHX2 GATA3 GATAD1 LIG3 RFFL RNU6-840P NLE1 GC17P035006 CCT6B
GH17G035533 1.9 FANTOM5 Ensembl ENCODE dbSUPER 4.2 -448.3 -448344 9.0 HDGF PKNOX1 ATF1 ARNT WRNIP1 ZNF2 YY1 TCF12 ZNF143 KLF13 AP2B1 SLFN12L CCL5 PEX12 SLFN5 TAF5LP1 GAS2L2 SLFN11 CCL14 RFFL
GH17G035345 1.2 FANTOM5 Ensembl ENCODE 6.5 -257.0 -256972 2.2 SUZ12 CEBPB CHD1 CBX2 MAX RAD21 NR2F2 ZNF121 CBX8 EGR1 RFFL SLFN5 SLFN11 ZNF830 SLFN14 GC17P035345 LOC105371933
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around RFFL on UCSC Golden Path with GeneCards custom track

Promoters for RFFL Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000093443 529 2001 HDGF FOXA2 PKNOX1 MLX AGO1 WRNIP1 ARID4B SIN3A DMAP1 SLC30A9

Genomic Location for RFFL Gene

Chromosome:
17
Start:
35,005,990 bp from pter
End:
35,089,329 bp from pter
Size:
83,340 bases
Orientation:
Minus strand

Genomic View for RFFL Gene

Genes around RFFL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RFFL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RFFL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RFFL Gene

Proteins for RFFL Gene

  • Protein details for RFFL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8WZ73-RFFL_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase rififylin
    Protein Accession:
    Q8WZ73
    Secondary Accessions:
    • E1P633
    • Q8NHW0
    • Q8TBY7
    • Q96BE6

    Protein attributes for RFFL Gene

    Size:
    363 amino acids
    Molecular mass:
    40514 Da
    Quaternary structure:
    • Interacts with CASP8 and CASP10. Interacts with RIPK1 (via protein kinase domain); involved in RIPK1 ubiquitination. Interacts with PRR5L. Interacts (via RING-type zinc finger) with p53/TP53; involved in p53/TP53 ubiquitination. Interacts (via RING-type zinc finger) with MDM2; the interaction stabilizes MDM2.

    Three dimensional structures from OCA and Proteopedia for RFFL Gene

    Alternative splice isoforms for RFFL Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RFFL Gene

Selected DME Specific Peptides for RFFL Gene

Q8WZ73:
  • IDCVLLECGHMVTCTKCGKRM
  • GCCEKWEL
  • VRQLKEILARNFVNY

Post-translational modifications for RFFL Gene

  • 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.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for RFFL Gene

Gene Families for RFFL Gene

Suggested Antigen Peptide Sequences for RFFL Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q8WZ73

UniProtKB/Swiss-Prot:

RFFL_HUMAN :
  • The RING-type zinc finger is required for the ubiquitination of target proteins.
Domain:
  • The RING-type zinc finger is required for the ubiquitination of target proteins.
  • The FYVE-type zinc finger domain is required for localization to the recycling endosome membranes and the function in endocytic recycling.
genes like me logo Genes that share domains with RFFL: view

Function for RFFL Gene

Molecular function for RFFL Gene

UniProtKB/Swiss-Prot CatalyticActivity:
S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.
UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction:
Down-regulated upon DNA damage.

Enzyme Numbers (IUBMB) for RFFL Gene

Gene Ontology (GO) - Molecular Function for RFFL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 15069192
GO:0002039 p53 binding IPI 17121812
GO:0005515 protein binding IPI 22609986
GO:0008270 zinc ion binding IEA --
GO:0016740 transferase activity IEA --
genes like me logo Genes that share ontologies with RFFL: view
genes like me logo Genes that share phenotypes with RFFL: view

Animal Models for RFFL Gene

MGI Knock Outs for RFFL:

Animal Model Products

  • Taconic Biosciences Mouse Models for RFFL

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for RFFL
  • Applied Biological Materials Clones for RFFL

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RFFL Gene

Localization for RFFL Gene

Subcellular locations from UniProtKB/Swiss-Prot for RFFL Gene

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

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RFFL gene
Compartment Confidence
plasma membrane 5
nucleus 5
endosome 5
cytosol 4
extracellular 1

Gene Ontology (GO) - Cellular Components for RFFL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 NOT Golgi membrane IDA 18450452
GO:0002947 colocalizes_with tumor necrosis factor receptor superfamily complex IDA 18450452
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IDA,IEA 15069192
GO:0005764 NOT lysosome IDA 18450452
genes like me logo Genes that share ontologies with RFFL: view

Pathways & Interactions for RFFL Gene

genes like me logo Genes that share pathways with RFFL: view

UniProtKB/Swiss-Prot Q8WZ73-RFFL_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

Gene Ontology (GO) - Biological Process for RFFL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006511 ubiquitin-dependent protein catabolic process IMP 18450452
GO:0006915 apoptotic process IEA --
GO:0010762 regulation of fibroblast migration ISS --
GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway IMP 18450452
GO:0016567 protein ubiquitination IEA --
genes like me logo Genes that share ontologies with RFFL: view

No data available for SIGNOR curated interactions for RFFL Gene

Drugs & Compounds for RFFL Gene

No Compound Related Data Available

Transcripts for RFFL Gene

Unigene Clusters for RFFL Gene

Ring finger and FYVE-like domain containing E3 ubiquitin protein ligase:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for RFFL
  • Applied Biological Materials Clones for RFFL

Alternative Splicing Database (ASD) splice patterns (SP) for RFFL Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b · 7c ^ 8 ^ 9a · 9b · 9c · 9d · 9e ^ 10 ^ 11 ^ 12
SP1: - - - - - - - -
SP2: -
SP3: - - - - - - -
SP4: -
SP5: - - - - -
SP6: - - - -
SP7: - - - - -
SP8: - - - - - - - - - - - - - - - -
SP9: - - - - - - -
SP10: - -

Relevant External Links for RFFL Gene

GeneLoc Exon Structure for
RFFL
ECgene alternative splicing isoforms for
RFFL

Expression for RFFL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for RFFL Gene

Protein differential expression in normal tissues from HIPED for RFFL Gene

This gene is overexpressed in Pancreas (32.4), Peripheral blood mononuclear cells (11.5), Spinal cord (8.6), and Frontal cortex (8.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for RFFL Gene



Protein tissue co-expression partners for RFFL Gene

NURSA nuclear receptor signaling pathways regulating expression of RFFL Gene:

RFFL

SOURCE GeneReport for Unigene cluster for RFFL Gene:

Hs.13680

mRNA Expression by UniProt/SwissProt for RFFL Gene:

Q8WZ73-RFFL_HUMAN
Tissue specificity: Ubiquitous. Detected in spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.

Evidence on tissue expression from TISSUES for RFFL Gene

  • Liver(4.4)
  • Nervous system(3.4)
genes like me logo Genes that share expression patterns with RFFL: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for RFFL Gene

Orthologs for RFFL Gene

This gene was present in the common ancestor of animals.

Orthologs for RFFL Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RFFL 34 35
  • 99.82 (n)
dog
(Canis familiaris)
Mammalia RFFL 34 35
  • 90.08 (n)
rat
(Rattus norvegicus)
Mammalia Rffl 34
  • 89.02 (n)
mouse
(Mus musculus)
Mammalia Rffl 34 16 35
  • 88.89 (n)
cow
(Bos Taurus)
Mammalia RFFL 34 35
  • 86.42 (n)
oppossum
(Monodelphis domestica)
Mammalia RFFL 35
  • 74 (a)
OneToOne
chicken
(Gallus gallus)
Aves RFFL 34 35
  • 69.63 (n)
tropical clawed frog
(Silurana tropicalis)
Amphibia rffl 34
  • 61.08 (n)
zebrafish
(Danio rerio)
Actinopterygii zgc:77828 34
  • 62.04 (n)
RFFL (1 of 2) 35
  • 58 (a)
OneToMany
RFFL (2 of 2) 35
  • 57 (a)
OneToMany
Dr.29063 34
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4743 34
fruit fly
(Drosophila melanogaster)
Insecta CG17019 35
  • 18 (a)
OneToMany
Species where no ortholog for RFFL was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for RFFL Gene

ENSEMBL:
Gene Tree for RFFL (if available)
TreeFam:
Gene Tree for RFFL (if available)

Paralogs for RFFL Gene

Paralogs for RFFL Gene

(1) SIMAP similar genes for RFFL Gene using alignment to 5 proteins:

genes like me logo Genes that share paralogs with RFFL: view

Variants for RFFL Gene

Sequence variations from dbSNP and Humsavar for RFFL Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type
rs1000026246 -- 35,030,608(+) TTTTG(C/T)ATTTT intron-variant
rs1000037223 -- 35,018,726(+) GGCAA(A/G)ATCAA intron-variant
rs1000058779 -- 35,039,382(+) ACCCA(A/G)CTAAT intron-variant
rs1000060753 -- 35,077,921(+) GGTCT(C/G)CAAGA intron-variant
rs1000066561 -- 35,069,720(+) ATGCA(C/T)CCTAA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RFFL Gene

Variant ID Type Subtype PubMed ID
esv3640438 CNV loss 21293372
nsv2035 CNV deletion 18451855

Variation tolerance for RFFL Gene

Residual Variation Intolerance Score: 83% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.27; 25.31% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for RFFL Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
RFFL

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RFFL Gene

Disorders for RFFL Gene

Relevant External Links for RFFL

Genetic Association Database (GAD)
RFFL
Human Genome Epidemiology (HuGE) Navigator
RFFL
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
RFFL

No disorders were found for RFFL Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for RFFL Gene

Publications for RFFL Gene

  1. Over-expression of Rififylin, a new RING finger and FYVE-like domain-containing protein, inhibits recycling from the endocytic recycling compartment. (PMID: 15229288) Coumailleau F. … Cohen-Tannoudji M. (Mol. Biol. Cell 2004) 2 3 22 64
  2. Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2. (PMID: 15576038) Tibbetts M.D. … Shi Y. (Structure 2004) 3 4 22 64
  3. PRR5L degradation promotes mTORC2-mediated PKC-delta phosphorylation and cell migration downstream of Galpha12. (PMID: 22609986) Gan X. … Wu D. (Nat. Cell Biol. 2012) 3 4 64
  4. An approach based on a genome-wide association study reveals candidate loci for narcolepsy. (PMID: 20677014) Shimada M. … Tokunaga K. (Hum. Genet. 2010) 3 46 64
  5. Common variants at ten loci influence QT interval duration in the QTGEN Study. (PMID: 19305408) Newton-Cheh C. … Stricker B.H. (Nat. Genet. 2009) 3 46 64

Products for RFFL Gene

  • Addgene plasmids for RFFL

Sources for RFFL Gene

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