RFFL explained

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.^{[1] [2]} RFFL is also known as CARP2/FRING/CARP-2/RNF189;/RNF34L/RIFIFYLIN^[3] and associate with endosomes.^[4] RFFL is known to affect cardiac repolarization,^[5] Cystic fibrosis transmembrane conductance regulator (CFTR) ubiquitination,^[6] and mitochondrial clearance by affecting Parkin/PRKN recruitment.

Interactors

• ATXN3
• MDM2
• OPTN
• Parkin
• RAB10
• RNF34
• STUB1
• VCP

Further reading

• Tibbetts MD, Shiozaki EN, Gu L, McDonald ER, El-Deiry WS, Shi Y . Crystal structure of a FYVE-type zinc finger domain from the caspase regulator CARP2 . Structure . 12 . 12 . 2257–2263 . December 2004 . 15576038 . 10.1016/j.str.2004.10.007 . free .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–12135 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . free . 2004PNAS..10112130B .
• McDonald ER, El-Deiry WS . Suppression of caspase-8- and -10-associated RING proteins results in sensitization to death ligands and inhibition of tumor cell growth . Proceedings of the National Academy of Sciences of the United States of America . 101 . 16 . 6170–6175 . April 2004 . 15069192 . 395941 . 10.1073/pnas.0307459101 . free . 2004PNAS..101.6170M .

Notes and References

1. Coumailleau F, Das V, Alcover A, Raposo G, Vandormael-Pournin S, Le Bras S, Baldacci P, Dautry-Varsat A, Babinet C, Cohen-Tannoudji M . 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 . October 2004 . 15229288 . 519139 . 10.1091/mbc.E04-04-0274 .
2. Web site: Entrez Gene: RFFL ring finger and FYVE-like domain containing 1.
3. Web site: RFFL ring finger and FYVE like domain containing E3 ubiquitin protein ligase [Homo sapiens (human)] - Gene - NCBI ]. 2024-06-12 . www.ncbi.nlm.nih.gov.
4. Ravindran R, Velikkakath AK, Narendradev ND, Chandrasekharan A, Santhoshkumar TR, Srinivasula SM . Endosomal-associated RFFL facilitates mitochondrial clearance by enhancing PRKN/parkin recruitment to mitochondria . Autophagy . 18 . 12 . 2851–2864 . December 2022 . 35373701 . 9673925 . 10.1080/15548627.2022.2052460 .
5. Kabakov AY, Roder K, Bronk P, Turan NN, Dhakal S, Zhong M, Lu Y, Zeltzer ZA, Najman-Licht YB, Karma A, Koren G . 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 . March 2024 . 38367666 . 10.1016/j.jbc.2024.105759 . free . 10945274 .
6. Okiyoneda T, Veit G, Sakai R, Aki M, Fujihara T, Higashi M, Susuki-Miyata S, Miyata M, Fukuda N, Yoshida A, Xu H, Apaja PM, Lukacs GL . Chaperone-Independent Peripheral Quality Control of CFTR by RFFL E3 Ligase . Developmental Cell . 44 . 6 . 694–708.e7 . March 2018 . 29503157 . 6447300 . 10.1016/j.devcel.2018.02.001 .