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

Summary

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, Nov 2024]
Expression: Ubiquitous expression in thyroid (RPKM 18.0), esophagus (RPKM 12.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

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_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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).
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.
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.
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.
Observational study of gene-disease association. (HuGE Navigator)
Title: An approach based on a genome-wide association study reveals candidate loci for narcolepsy.
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.
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.
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.

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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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

D17S822E (e-PCR)
- UniSTS:28243

D17S1725E (e-PCR)
- UniSTS:153959

D17S2135 (e-PCR)
- UniSTS:19816

A008R31 (e-PCR)
- UniSTS:25215

D11S3114 (e-PCR)
- UniSTS:152207

D17S1708 (e-PCR)
- UniSTS:40595

D17S822E (e-PCR)
- UniSTS:147373

WI-16693 (e-PCR)
- UniSTS:43953

A008P23 (e-PCR)
- UniSTS:43954

RH69286 (e-PCR)
- UniSTS:50876

SHGC-32545 (e-PCR)
- UniSTS:18631

G49586 (e-PCR)
- UniSTS:109255

WI-15077 (e-PCR)
- UniSTS:7903

D17S822E (e-PCR)
- UniSTS:46839

Readthrough RAD51L3-RFFL

Readthrough gene: RAD51L3-RFFL, Included gene: RAD51D

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 involved in execution phase of apoptosis	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 more info	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

EC 2.3.2.27

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)

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

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

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

35005990..35089226 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

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

NM_057178.3: Suppressed sequence

Description

NM_057178.3: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.