Table 4.
Top 20 E3 ubiquitin ligases and their molecular functions
| Bayesian Ranking | Gene Symbol | Class | Annotation | Functional Notes |
|---|---|---|---|---|
| 1 | Nedd4 | HECTc | E3 ubiquitin-protein ligase NEDD4 isoform 1 | Specifically ubiquitinates ‘Lys-63’ in target proteins. Involved in pathway leading to degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites. Ubiquitinates FGFR1, TNK2, and BRAT1. Promotes ubiquitination of RAPGEF2. |
| 1 | Nedd4L | HECTc | E3 ubiquitin-protein ligase NEDD4-like isoform 6 | Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, Nav1.2, Nav1.3, Nav1.5, Nav1.7, Nav1.8, Kv1.3, EAAT1, or CLC5. Ubiquitinates BRAT1. Plays a role in dendrite formation by melanocytes. |
| 3 | Amfr | RING | autocrine motility factor receptor | Polyubiquitinates number of proteins. Is a component of VCP/p97-Amfr/gp78 complex. Involved in last step of ERAD |
| 4 | Stub1 | UBOX | E3 ubiquitin-protein ligase CHIP isoform b | Catalyzes polyubiquitination by amplyfying the HUWE1/Arf-bp1-dependent monoubiquitination. Modulates the activity of several chaperone complexes, including Hsp70, Hsc70, and Hsp90. |
| 5 | Itch | HECTc | E3 ubiquitin-protein ligase Itchy homolog isoform 3 | Involved in the control of inflammatory signaling pathways |
| 6 | Zfpl1 | RING | E3 ubiquitin-protein ligase ZFP91 isoform 2 | ER to Golgi transport. Involved in maitenance of the integrity of the cis-Golgi, possibly via its interation with Golga2/GM130. Transmembrane protein. |
| 7 | Trip12 | HECTc | E3 ubiquitin-protein ligase TRIP12 isoform a | Involved in ubiquitin fusion degradation (UDF). Key regulator of DNA damage response. Mediates ubiquitination of isoform p19ARF/ARF of CDKN2A in normal cells. |
| 8 | Prpf19 | UBOX | premRNA-processing factor 19 | Core component of PRP19C/Prp19 complex/NTC/Nineteen complex. Mediates polyubiquitination of U4 spliceosomal protein Prpf3. May couple the transcriptional and spliceosomal machineries. |
| 9 | Syvn1 | RING | synovial apoptosis inhibitor 1, synoviolin | Accepts ubiquitin specifically from ER-associated UBC7. Component of ERAD. Protects cells from ER stress-induced apoptosis. |
| 10 | Anapc11 | RING | anaphase-promoting complex subunit 11 isoform 2 | Catalytic component of anaphase promoting complex/cyclosome. Moderate levels in kidney. |
| 11 | March5 | RING | E3 ubiquitin-protein ligase MARCH5 | Mitochondrial E3 ligase. Plays a crucial role in control of mitochondrial morphology. Acts as positive regulator of mitochondrial fission. May play role in prevention of cell senescence. Transmembrane protein. |
| 12 | Rnf130 | RING | E3 ubiquitin-protein ligase RNF130 isoform 2 precursor | Transmembrane protein. |
| 13 | Ppil2 | RING | peptidyl-prolyl cis-trans isomerase-like 2 isoform b | By ′Lys-48′-linked polyubiquitination of proteins, could target them for proteasomal degradation. May catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides thereby assisting the folding of proteins. |
| 14 | Brap | RING | BRCA1 associated protein | A RAS responsive E3 ligase. Negatively regulates MAP kinase activation. May act as a cytoplasmic retention protein with role in nuclear transport. |
| 15 | Smurf2 | RING | SMAD specific E3 ubiquitin protein ligase 2 | Interacts with SMAD1 and SMAD7 to trigger their ubiquitination and proteasome-dependent degradation. Coexpression with SMAD1 results in considerable decrease in steady-state level of SMAD1 protein. |
| 16 | Trim25 | RING | E3 ubiquitin/ISG15 ligase TRIM25 | Also an ISG15 ligase. Involved in immune defense by ubiquitinating DDX58. Mediates estrogen action in various target organs. Mediates ubiquitination and subsequent proteasomal degradation of ZFHX3. |
| 17 | Cyhr1 | RING | cysteine and histidine-rich protein 1 isoform 2 precursor | No information on function. |
| 18 | Rnf128 | RING | E3 ubiquitin-protein ligase RNF128 isoform 1 precursor | Inhibitor of cytokine gene transcription. Sensitizes ectoderm to respond to neural-inducing signals. Ubiquitinates ARPC5 and COR1A. Transmembrane protein. |
| 18 | Rnf167 | RING | E3 ubiquitin-protein ligase RNF167 precursor | Transmembrane protein. |
| 18 | Rnf5 | RING | ring finger protein 5, E3 ubiquitin protein ligase | May function with E2 ubiquitin-conjugating enzymes UBE2D1/UBCH5A and UBE2D2/UBC4. Mediates ubiquitination of PXN/paxillin and sopA. May be involved in regulation of cell motility and localization of PXN/paxillin. Mediates polyubiquitination of JKAMP. Mediates polyubiquitination of TMEM173. |
Functional notes on the top 20 E3 ubiquitin ligases found with Bayesian analysis. The functional notes were found in the FUNCTION fields of UniProt records.