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 is also known as CARP2/FRING/CARP-2/RNF189;/RNF34L/RIFIFYLIN [7] and associate with endosomes. [8] RFFL is known to affect cardiac repolarization, [9] Cystic fibrosis transmembrane conductance regulator (CFTR) ubiquitination, [10] and mitochondrial clearance by affecting Parkin/PRKN recruitment. [8]
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 thing 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.
Ubiquitin-conjugating enzyme E2 L3 (UBE2L3), also called UBCH7, is a protein that in humans is encoded by the UBE2L3 gene. As an E2 enzyme, UBE2L3 participates in ubiquitination to target proteins for degradation. The role of UBE2L3 in the ubiquitination of the NF-κB precursor implicated it in various major autoimmune diseases, including rheumatoid arthritis (RA), celiac disease, Crohn's disease (CD), and systemic lupus erythematosus.
Ubiquitin-conjugating enzyme E2 D1 is a protein that in humans is encoded by the UBE2D1 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 G2 is a protein that in humans is encoded by the UBE2G2 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.
E3 ubiquitin-protein ligase NRDP1 is an enzyme that in humans is encoded by the RNF41 gene.
Tripartite motif-containing protein 32 is a protein that in humans is encoded by the TRIM32 gene. Since its discovery in 1995, TRIM32 has been shown to be implicated in a number of diverse biological pathways.
RanBP-type and C3HC4-type zinc finger-containing protein 1 is a protein that in humans is encoded by the RBCK1 gene.
E3 ubiquitin-protein ligase RNF34 is an enzyme that in humans is encoded by the RNF34 gene.
RING finger protein 115 is a protein, that in humans, is encoded by the RNF115 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.
E3 ubiquitin-protein ligase RNF128 is an enzyme that in humans is encoded by the RNF128 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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