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. [5] [6] RFFL associates with endosomes. [7] RFFL is known to affect cardiac repolarization, [8] Cystic fibrosis transmembrane conductance regulator (CFTR) ubiquitination, [9] and mitochondrial clearance by affecting Parkin/PRKN recruitment. [7]
A ubiquitin ligase is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another protein by some mechanism. The ubiquitin, once it reaches its destination, ends up being attached by an isopeptide bond to a lysine residue, which is part of the target protein. E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases regulates diverse areas such as cell trafficking, DNA repair, and signaling and is of profound importance in cell biology. E3 ligases are also key players in cell cycle control, mediating the degradation of cyclins, as well as cyclin dependent kinase inhibitor proteins. The human genome encodes over 600 putative E3 ligases, allowing for tremendous diversity in substrates.
ITCH is a HECT domain–containing E3 ubiquitin ligase that is ablated in non-agouti-lethal 18H mice. Itchy mice develop a severe immunological phenotype after birth that includes hyperplasia of lymphoid and hematopoietic cells, and stomach and lung inflammation. In humans ITCH deficiency causes altered physical growth, craniofacial morphology defects, defective muscle development, and aberrant immune system function. The ITCH gene is located on chromosome 20 in humans. ITCH contains a C2 domain, proline-rich region, WW domains, HECT domain, and multiple amino acids that are phosphorylated and ubiquitinated.
STUB1 is a human gene that codes for the protein CHIP.
E3 ubiquitin-protein ligase RING2 is an enzyme that in humans is encoded by the RNF2 gene.
E3 ubiquitin-protein ligase Topors is an enzyme that in humans is encoded by the TOPORS gene.
RING-box protein 2 is a protein that in humans is encoded by the RNF7 gene.
Ubiquitin-conjugating enzyme E2 E3 is a protein that in humans is encoded by the UBE2E3 gene.
Ubiquitin/ISG15-conjugating enzyme E2 L6 is a protein that in humans is encoded by the UBE2L6 gene.
The human gene UBR1 encodes the enzyme ubiquitin-protein ligase E3 component n-recognin 1.
E3 ubiquitin-protein ligase RNF19A is an enzyme that in humans is encoded by the RNF19A gene.
Ubiquitin-conjugating enzyme E2 G1 is a protein that in humans is encoded by the UBE2G1 gene.
E3 ubiquitin-protein ligase NRDP1 is an enzyme that in humans is encoded by the RNF41 gene.
RanBP-type and C3HC4-type zinc finger-containing protein 1 is a protein that in humans is encoded by the RBCK1 gene.
Baculoviral IAP repeat-containing protein 6 is a protein that in humans is encoded by the BIRC6 gene.
E3 ubiquitin-protein ligase RNF34 is an enzyme that in humans is encoded by the RNF34 gene.
E3 ubiquitin-protein ligase UHRF2 is an enzyme that in humans is encoded by the UHRF2 gene.
E3 ubiquitin-protein ligase MARCH5, also known as membrane-associated ring finger (C3HC4) 5, is an enzyme that, in humans, is encoded by the MARCH5 gene. It is localized in the mitochondrial outer membrane and has four transmembrane domains.
E3 ubiquitin-protein ligase RNF125 is an enzyme that in humans is encoded by the RNF125 gene.
Mitochondrial E3 ubiquitin protein ligase 1 (MUL1) is an enzyme that in humans is encoded by the MUL1 gene on chromosome 1. This enzyme localizes to the outer mitochondrial membrane, where it regulates mitochondrial morphology and apoptosis through multiple pathways, including the Akt, JNK, and NF-κB. Its proapoptotic function thus implicates it in cancer and Parkinson's disease.
RNF144A is an E3 ubiquitin ligase belonging to the RING-between RING (RBR) family of ubiquitin ligases, whose specific members have been shown to function as RING-HECT hybrid E3 ligases. RNF144A is most closely related to RNF144B at the protein level, and the two proteins together comprise a subdomain within the RBR family of proteins. The ubiquitin ligase activity of RNF144A catalyzes ubiquitin linkages at the K6-, K11- and K48- positions of ubiquitin in vitro, and is regulated by self-association through its transmembrane domain.
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