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
  • E3 Ubiquitin-Protein Ligase Rififylin 3 4
  • Caspase Regulator CARP2 3 4
  • RING Finger Protein 189 3 4
  • CARP-2 3 4
  • RNF189 3 4
  • RNF34L 3 4
  • Ring Finger And FYVE-Like Domain Containing 1 3
  • Ring Finger And FYVE-Like Domain Containing 2
  • 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 52
  • CARP2 3
  • FRING 3
  • Fring 4

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 Gene Expression and TNFR1 Pathway. 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.

UniProtKB/Swiss-Prot Summary 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

Additional gene information for RFFL Gene

No data available for Entrez Gene Summary , CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for RFFL Gene

Genomics for RFFL Gene

GeneHancer (GH) Regulatory Elements for RFFL Gene

Promoters and enhancers for RFFL Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH17J035083 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 520.4 +2.2 2166 6.6 RXRA CTCF SIN3A POLR2G NCOR1 PHF8 ZNF10 EP300 ZBTB26 SAP30 RFFL LIG3 SLFN5 ZNF830 CCT6B NLE1 RPL37P22 ENSG00000267618 RAD51L3-RFFL
GH17J035062 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE dbSUPER 515.8 +25.1 25102 3.9 EP300 FOXK2 ZNF217 SIN3A TCF12 POLR2G SP1 NCOR1 JUND FOS RFFL piR-43106-092 LIG3 RNU6-840P CCT6B ENSG00000267457 ENSG00000267618 RAD51L3-RFFL
GH17J035020 Promoter/Enhancer 1.6 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 501.6 +66.5 66531 4 TCF12 FOS CTCF ZIC2 POLR2A RBM25 NR2F2 REST NR3C1 JUND RFFL LIG3 RNU6-840P SLFN12L NLE1 SLFN5 ZNF830 CCT6B ENSG00000273687 RF01210-163
GH17J035067 Promoter/Enhancer 1.1 EPDnew ENCODE dbSUPER 504.8 +20.4 20353 2.3 MEF2B SMARCA5 BATF MAFK EBF1 TBP NFATC3 TBX21 TFAP4 ZNF217 RFFL ENSG00000267457 piR-43106-092 ENSG00000267618 RAD51L3-RFFL
GH17J035058 Promoter 0.3 EPDnew 500.3 +31.1 31089 0.1 RFFL RF01210-163 piR-43106-092 ENSG00000267618 RAD51L3-RFFL
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around RFFL on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for RFFL

Top Transcription factor binding sites by QIAGEN in the RFFL gene promoter:
  • c-Myb
  • Cart-1
  • CUTL1
  • FOXF2
  • Ik-2
  • Max1
  • POU2F1
  • POU2F1a

Genomic Locations for RFFL Gene

Genomic Locations for RFFL Gene
chr17:35,005,990-35,089,329
(GRCh38/hg38)
Size:
83,340 bases
Orientation:
Minus strand
chr17:33,333,009-33,416,348
(GRCh37/hg19)
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

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for RFFL Gene

Blocks:
  • DNA-binding SAP
  • Zn-finger, RING
  • Zn-finger, FYVE type
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for RFFL Gene

GenScript: Design optimal peptide antigens:
  • RING finger protein 34-like (RFFL_HUMAN)

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 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 CatalyticActivity:
Reaction=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.; EC=2.3.2.27; Evidence=. ;.
UniProtKB/Swiss-Prot Induction:
Down-regulated upon DNA damage.

Enzyme Numbers (IUBMB) for RFFL Gene

Phenotypes From GWAS Catalog 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:0016740 transferase activity IEA --
GO:0019901 protein kinase binding IPI 18450452
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:
  • Rffl Rffl<tm1Cota>

Animal Model Products

  • Taconic Biosciences Mouse Models for RFFL

Clone Products

  • Addgene plasmids 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 2
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for RFFL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 NOT Golgi membrane IDA 18450452
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA,IDA 15069192
GO:0005764 NOT lysosome IDA 18450452
GO:0005768 endosome IEA --
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

mRNA/cDNA for RFFL Gene

2 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Clone Products

  • Addgene plasmids 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

Expression for RFFL Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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, MaxQB, and MOPED for RFFL Gene



Protein tissue co-expression partners for RFFL Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for 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

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 31 30
  • 99.82 (n)
OneToOne
dog
(Canis familiaris)
Mammalia RFFL 31 30
  • 90.08 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Rffl 30
  • 89.02 (n)
mouse
(Mus musculus)
Mammalia Rffl 17 31 30
  • 88.89 (n)
cow
(Bos Taurus)
Mammalia RFFL 31 30
  • 86.42 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia RFFL 31
  • 74 (a)
OneToOne
chicken
(Gallus gallus)
Aves RFFL 31 30
  • 69.63 (n)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rffl 30
  • 61.08 (n)
zebrafish
(Danio rerio)
Actinopterygii zgc:77828 30
  • 62.04 (n)
RFFL (1 of 2) 31
  • 58 (a)
OneToMany
RFFL (2 of 2) 31
  • 57 (a)
OneToMany
Dr.29063 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.4743 30
fruit fly
(Drosophila melanogaster)
Insecta CG17019 31
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for RFFL: view image

Paralogs for RFFL Gene

Paralogs for RFFL Gene

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

  • RFFL_HUMAN
  • C9JE27_HUMAN
  • J3KSI3_HUMAN
  • J3KSU7_HUMAN
  • J3QR17_HUMAN
genes like me logo Genes that share paralogs with RFFL: view

Variants for RFFL Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for RFFL Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
713381 Benign: not provided 35,021,522(-) C/T MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
736128 Benign: not provided 35,021,396(-) G/T MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT

Additional dbSNP identifiers (rs#s) for RFFL Gene

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)

Additional Variant Information for RFFL Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for RFFL Gene

Additional Disease Information for RFFL

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

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 (Molecular biology of the cell 2004) 2 3 23 54
  2. Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2. (PMID: 15576038) Tibbetts MD … Shi Y (Structure (London, England : 1993) 2004) 3 4 23 54
  3. PRR5L degradation promotes mTORC2-mediated PKC-δ phosphorylation and cell migration downstream of Gα12. (PMID: 22609986) Gan X … Wu D (Nature cell biology 2012) 3 4 54
  4. An approach based on a genome-wide association study reveals candidate loci for narcolepsy. (PMID: 20677014) Shimada M … Tokunaga K (Human genetics 2010) 3 41 54
  5. Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity. (PMID: 19773279) Hosgood HD … Lan Q (Occupational and environmental medicine 2009) 3 41 54

Products for RFFL Gene

Sources for RFFL Gene