RFFL

RFFL
Identifiers
Aliases	RFFL, CARP-2, CARP2, FRING, RIFIFYLIN, RNF189, RNF34L, ring finger and FYVE-like domain containing E3 ubiquitin protein ligase, ring finger and FYVE like domain containing E3 ubiquitin protein ligase
External IDs	OMIM: 609735; MGI: 1914588; GeneCards: RFFL
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1Y02
Enzyme activity
Gene location (Human)
Chr.	Chromosome 17 (human)
End	35,089,319 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	82,762,036 bp
RNA expression pattern
	Top expressed in
	inferior ganglion of vagus nerve; ; secondary oocyte; ; pancreatic epithelial cell; ; buccal mucosa cell; ; corpus callosum; ; mucosa of ileum; ; spinal cord; ; amniotic fluid; ; subthalamic nucleus; ; C1 segment;
	Top expressed in
	granulocyte; ; olfactory epithelium; ; zygote; ; secondary oocyte; ; lacrimal gland; ; seminiferous tubule; ; spermatid; ; blood; ; epithelium of stomach; ; primary oocyte;
	More reference expression data
	n/a
Gene ontology
Molecular function	p53 binding; metal ion binding; protease binding; protein binding; protein kinase binding; ubiquitin protein ligase binding; ubiquitin protein ligase activity; transferase activity;
Cellular component	cytoplasm; cytosol; endosome; membrane; plasma membrane; Golgi membrane; tumor necrosis factor receptor superfamily complex; recycling endosome membrane; lysosome; endosome membrane; nucleoplasm;
Biological process	regulation of TOR signaling; ubiquitin-dependent protein catabolic process; negative regulation of tumor necrosis factor-mediated signaling pathway; protein K48-linked ubiquitination; negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; protein ubiquitination; negative regulation of signal transduction by p53 class mediator; regulation of fibroblast migration; proteasome-mediated ubiquitin-dependent protein catabolic process; apoptotic process;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	117584
	67338
	ENSG00000092871
	ENSMUSG00000020696
	Q8WZ73
	Q6ZQM0
	NM_001017368; NM_057178
	NM_001007465; NM_001164569; NM_001164570; NM_001164571; NM_026097
	NP_001017368
	NP_001007466; NP_001158041; NP_001158042; NP_001158043; NP_080373
	Wikidata
View/Edit Human	View/Edit Mouse

E3 ubiquitin-protein ligase RFFL (Ring Finger And FYVE Like Domain Containing E3 Ubiquitin) is a ubiquitin ligase enzyme that in humans is encoded by the RFFL gene. RFFL associates with endosomes. RFFL is known to affect cardiac repolarization, Cystic fibrosis transmembrane conductance regulator (CFTR) ubiquitination, and mitochondrial clearance by affecting Parkin/PRKN recruitment, and the regulation of mitochondrial morphology through the ubiquitination of mitofusin proteins. Proteomic studies suggest broader roles for RFFL, such as roles in lipid metabolism. Currently, only FYVE domain of RFFL strcuture is solved.

Interactors

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000092871 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020696 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Coumailleau F, Das V, Alcover A, Raposo G, Vandormael-Pournin S, Le Bras S, et al. (October 2004). "Over-expression of Rififylin, a new RING finger and FYVE-like domain-containing protein, inhibits recycling from the endocytic recycling compartment". Molecular Biology of the Cell. 15 (10): 4444–4456. doi:10.1091/mbc.E04-04-0274. PMC 519139. PMID 15229288.
↑ "Entrez Gene: RFFL ring finger and FYVE-like domain containing 1".
1 2 Ravindran R, Velikkakath AK, Narendradev ND, Chandrasekharan A, Santhoshkumar TR, Srinivasula SM (December 2022). "Endosomal-associated RFFL facilitates mitochondrial clearance by enhancing PRKN/parkin recruitment to mitochondria". Autophagy. 18 (12): 2851–2864. doi:10.1080/15548627.2022.2052460. PMC 9673925. PMID 35373701.
↑ Kabakov AY, Roder K, Bronk P, Turan NN, Dhakal S, Zhong M, et al. (March 2024). "E3 ubiquitin ligase rififylin has yin and yang effects on rabbit cardiac transient outward potassium currents (I_to) and corresponding channel proteins". The Journal of Biological Chemistry. 300 (3) 105759. doi:10.1016/j.jbc.2024.105759. PMC 10945274. PMID 38367666.
↑ Okiyoneda T, Veit G, Sakai R, Aki M, Fujihara T, Higashi M, et al. (March 2018). "Chaperone-Independent Peripheral Quality Control of CFTR by RFFL E3 Ligase". Developmental Cell. 44 (6): 694–708.e7. doi:10.1016/j.devcel.2018.02.001. PMC 6447300. PMID 29503157.
↑ Narendradev ND, Ravindran R, Jain P, Chaudhary S, Velikkakath AK, Sudharman A, et al. (June 2025). "Endosomal RFFL ubiquitin ligase regulates mitochondrial morphology by targeting mitofusin 2". Journal of Cell Science. 138 (12) jcs263830. doi:10.1242/jcs.263830. PMC 12211564. PMID 40444323.
↑ Narendradev ND, Marathe S, Baboo S, McClatchy DB, Diedrich JK, Jain P, et al. (August 2025). "Quantitative Proteomic Analysis Reveals JMJD6 and DNAJB11 as Endogenous Substrates of E3 Ligase RFFL". Journal of Proteome Research. 24 (8): 3913–3930. doi:10.1021/acs.jproteome.5c00086. PMID 40568870.
↑ Tibbetts MD, Shiozaki EN, Gu L, McDonald ER, El-Deiry WS, Shi Y (December 2004). "Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2". Structure. 12 (12). London: 2257–2263. doi:10.1016/j.str.2004.10.007. PMID 15576038.

RFFL

Interactors

See also

References

Further reading