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RFFL ring finger and FYVE like domain containing E3 ubiquitin protein ligase [ Homo sapiens (human) ]

Gene ID: 117584, updated on 10-Dec-2024

Summary

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Official Symbol
RFFLprovided by HGNC
Official Full Name
ring finger and FYVE like domain containing E3 ubiquitin protein ligaseprovided by HGNC
Primary source
HGNC:HGNC:24821
See related
Ensembl:ENSG00000092871 MIM:609735; AllianceGenome:HGNC:24821
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CARP2; FRING; CARP-2; RNF189; RNF34L; RIFIFYLIN
Summary
Enables enzyme binding activity; p53 binding activity; and ubiquitin protein ligase activity. Involved in several processes, including negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; negative regulation of signal transduction; and protein K48-linked ubiquitination. Located in endosome membrane and plasma membrane. [provided by Alliance of Genome Resources, Dec 2024]
Expression
Ubiquitous expression in thyroid (RPKM 18.0), esophagus (RPKM 12.3) and 25 other tissues See more
Orthologs
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Genomic context

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See RFFL in Genome Data Viewer
Location:
17q12
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (35005990..35089226, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (35953906..36037140, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (33333009..33416245, complement)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene chaperonin containing TCP1 subunit 6B Neighboring gene Sharpr-MPRA regulatory region 18 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12049 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12050 Neighboring gene zinc finger protein 830 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8432 Neighboring gene DNA ligase 3 Neighboring gene RAD51L3-RFFL readthrough Neighboring gene oligosaccharyltransferase complex subunit pseudogene 7 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:33354498-33354674 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12051 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12054 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12053 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12052 Neighboring gene small nucleolar RNA U13 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr17:33390277-33391476 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12056 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12057 Neighboring gene ribosomal protein L37 pseudogene 22 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12058 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:33416287-33416938 Neighboring gene MPRA-validated peak2815 silencer Neighboring gene RNA, U6 small nuclear 840, pseudogene Neighboring gene RAD51 paralog D Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8435 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12059 Neighboring gene fibronectin type III domain containing 8 Neighboring gene notchless homolog 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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Related articles in PubMed

  1. Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2. Tibbetts MD, et al. Structure, 2004 Dec. PMID 15576038
  2. E3 ubiquitin ligase rififylin has yin and yang effects on rabbit cardiac transient outward potassium currents (I(to)) and corresponding channel proteins. Kabakov AY, et al. J Biol Chem, 2024 Mar. PMID 38367666, Free PMC Article
  3. CARPs regulate STUB1 and its pathogenic mutants aggregation kinetics by mono-ubiquitination. Sharma R, et al. FEBS J, 2023 Jul. PMID 36853170
  4. Positional cloning of quantitative trait nucleotides for blood pressure and cardiac QT-interval by targeted CRISPR/Cas9 editing of a novel long non-coding RNA. Cheng X, et al. PLoS Genet, 2017 Aug. PMID 28827789, Free PMC Article
  5. The Ubiquitin Ligase RNF34 Participates in the Peripheral Quality Control of CFTR (RNF34 Role in CFTR PeriQC). Taniguchi S, et al. Front Mol Biosci, 2022. PMID 35355508, Free PMC Article

See all (38) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. E3 ubiquitin ligase rififylin has yin and yang effects on rabbit cardiac transient outward potassium currents (Ito) and corresponding channel proteins.
    Title: E3 ubiquitin ligase rififylin has yin and yang effects on rabbit cardiac transient outward potassium currents (I(to)) and corresponding channel proteins.
  2. The integral function of the endocytic recycling compartment is regulated by RFFL-mediated ubiquitylation of Rab11 effectors.
    Title: The integral function of the endocytic recycling compartment is regulated by RFFL-mediated ubiquitylation of Rab11 effectors.
  3. RFFL is an important regulator of voltage-gated hERG potassium channel activity and therefore cardiac repolarization and that this ubiquitination-mediated regulation requires parts of the ERAD pathway.
    Title: Trafficking of the human ether-a-go-go-related gene (hERG) potassium channel is regulated by the ubiquitin ligase rififylin (RFFL).
  4. it is interesting to note that a human lncRNA does exist within the 5'-UTR intronic region of the human RFFL gene . Given the rat data, our study may serve as a translational foundation for considering this human lncRNA as a candidate regulator for cardiovascular diseases.
    Title: Positional cloning of quantitative trait nucleotides for blood pressure and cardiac QT-interval by targeted CRISPR/Cas9 editing of a novel long non-coding RNA.
  5. EGF, which signals through CRAF, and an activated BRAF mutant also activate PKC and stimulate cell migration through up-regulating RFFL expression.
    Title: Different Raf protein kinases mediate different signaling pathways to stimulate E3 ligase RFFL gene expression in cell migration regulation.
  6. data indicate AE induces caspase-8-mediated activation of mitochondrial death pathways by decreasing the stability of CARP mRNAs in a p53-independent manner.
    Title: Destabilization of CARP mRNAs by aloe-emodin contributes to caspase-8-mediated p53-independent apoptosis of human carcinoma cells.
  7. Observational study of gene-disease association. (HuGE Navigator)
    Title: An approach based on a genome-wide association study reveals candidate loci for narcolepsy.
  8. CARPs together with MDM2 enhance p53 degradation, thereby inhibiting p53-mediated cell death.
    Title: CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing MDM2.
  9. Meta-analysis and genome-wide association study of gene-disease association. (HuGE Navigator)
    Title: Common variants at ten loci influence QT interval duration in the QTGEN Study.
  10. acts at the level of endocytic vesicles to limit the intensity of TNF-induced NF-kappaB activation by the regulated elimination of a necessary signaling component within the receptor complex
    Title: CARP-2 is an endosome-associated ubiquitin ligase for RIP and regulates TNF-induced NF-kappaB activation.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Common variants at ten loci influence QT interval duration in the QTGEN Study.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Readthrough RAD51L3-RFFL

Readthrough gene: RAD51L3-RFFL, Included gene: RAD51D

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables p53 binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protease binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables ubiquitin protein ligase activity TAS
Traceable Author Statement
more info
  
enables ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of cysteine-type endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of signal transduction by p53 class mediator IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of tumor necrosis factor-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein K48-linked ubiquitination IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of TOR signaling IC
Inferred by Curator
more info
 PubMed 
involved_in regulation of fibroblast migration ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of signal transduction by p53 class mediator TAS
Traceable Author Statement
more info
  
involved_in ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
NOT located_in Golgi membrane IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol IEA
Inferred from Electronic Annotation
more info
  
located_in endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
NOT located_in lysosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane HDA PubMed 
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in recycling endosome membrane IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
E3 ubiquitin-protein ligase rififylin
Names
FYVE-RING finger protein SAKURA
RING finger and FYVE-like domain-containing protein 1
RING finger protein 189
RING-type E3 ubiquitin transferase rififylin
caspase 8 and 10 associated RING protein-2
caspase regulator CARP2
caspases-8 and -10-associated RING finger protein 2
ring finger and FYVE-like domain containing 1
NP_001017368.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001017368.2 → NP_001017368.1  E3 ubiquitin-protein ligase rififylin

    See identical proteins and their annotated locations for NP_001017368.1

    Status: VALIDATED

    Description
    Transcript Variant: This variant (2) represents the shorter transcript but encodes the supported protein.
    Source sequence(s)
    AC004223, BC028424, CK001659, CR933651
    Consensus CDS
    CCDS11286.1
    UniProtKB/Swiss-Prot
    E1P633, Q8NHW0, Q8TBY7, Q8WZ73, Q96BE6
    Related
    ENSP00000378096.3, ENST00000394597.7
    Conserved Domains (2) summary
    cd15770
    Location:44 → 92
    FYVE_CARP2; FYVE-like domain found in caspase regulator CARP2 and similar proteins
    cd16500
    Location:315 → 353
    RING-HC_CARP; RING finger, HC subclass, found in caspases-8 and -10-associated RING finger protein CARP-1, CARP-2 and similar proteins

RNA

  1. NR_037713.2 RNA Sequence

    Status: VALIDATED

    Description
    Transcript Variant: This variant (1) uses an alternate 5' exon, compared to variant 2. This variant is represented as non-coding due to the presence of an upstream ORF that is predicted to interfere with the translation of the downstream ORF, as found in variant 2. Translation of the upstream ORF renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AC004223, AK093112, BC028424, CR933651

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    35005990..35089226 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    35953906..36037140 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_057178.3: Suppressed sequence

    Description
    NM_057178.3: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8WZ73.1 GenPept UniProtKB/Swiss-Prot:Q8WZ73

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
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