| Tchem | E3 ubiquitin-protein ligase NEDD4 |
E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Specifically ubiquitinates 'Lys-63' in target proteins (PubMed:23644597). Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Promotes ubiquitination of RAPGEF2. According to PubMed:18562292 the direct link between NEDD4 and PTEN regulation through polyubiquitination described in PubMed:17218260 is questionable. Involved in ubiquitination of ERBB4 intracellular domain E4ICD. Involved in the budding of many viruses. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2. Involved in the ubiquitination of ebola virus VP40 protein and this ubiquitination plays a role in facilitating viral budding. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046).
This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN. [provided by RefSeq, Jul 2016]
This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN. [provided by RefSeq, Jul 2016]
Comments
Property Summary
| Ligand Count | 2 |
| NCBI Gene PubMed Count | 164 |
| PubMed Score | 259.82 |
| PubTator Score | 194.50 |
| Disease | Target Count |
|---|---|
| Bipolar Disorder | 666 |
| Disease | Target Count | P-value |
|---|---|---|
| glioblastoma | 5792 | 7.1e-08 |
| Astrocytoma, Pilocytic | 3081 | 4.8e-07 |
| pediatric high grade glioma | 1064 | 8.9e-07 |
| lung carcinoma | 2843 | 5.2e-06 |
| lung cancer | 4740 | 1.2e-02 |
| acute myeloid leukemia | 783 | 4.1e-02 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Skin disease | 66 | 0.0 | 3.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Liddle syndrome | 14 | 6.035 | 3.0 |
| Spinocerebellar ataxia type 31 | 8 | 4.657 | 2.3 |
| Pseudohypoaldosteronism | 23 | 3.53 | 1.8 |
| Charcot-Marie-Tooth disease type 1C | 5 | 3.419 | 1.7 |
| Cancer | 2499 | 3.379 | 1.7 |
| Hypertension | 396 | 3.041 | 1.5 |
| Disease | log2 FC | p |
|---|---|---|
| acute myeloid leukemia | -1.300 | 4.1e-02 |
| Astrocytoma, Pilocytic | 1.800 | 4.8e-07 |
| glioblastoma | 1.500 | 7.1e-08 |
| lung cancer | -1.200 | 1.2e-02 |
| lung carcinoma | -1.200 | 5.2e-06 |
| pediatric high grade glioma | 1.400 | 8.9e-07 |
MAQSLRLHFAARRSNTYPLSETSGDDLDSHVHMCFKRPTRISTSNVVQMKLTPRQTALAPLIKENVQSQE 1 - 70 RSSVPSSENVNKKSSCLQISLQPTRYSGYLQSSNVLADSDDASFTCILKDGIYSSAVVDNELNAVNDGHL 71 - 140 VSSPAICSGSLSNFSTSDNGSYSSNGSDFGSCASITSGGSYTNSVISDSSSYTFPPSDDTFLGGNLPSDS 141 - 210 TSNRSVPNRNTTPCEIFSRSTSTDPFVQDDLEHGLEIMKLPVSRNTKIPLKRYSSLVIFPRSPSTTRPTS 211 - 280 PTSLCTLLSKGSYQTSHQFIISPSEIAHNEDGTSAKGFLSTAVNGLRLSKTICTPGEVRDIRPLHRKGSL 281 - 350 QKKIVLSNNTPRQTVCEKSSEGYSCVSVHFTQRKAATLDCETTNGDCKPEMSEIKLNSDSEYIKLMHRTS 351 - 420 ACLPSSQNVDCQININGELERPHSQMNKNHGILRRSISLGGAYPNISCLSSLKHNCSKGGPSQLLIKFAS 421 - 490 GNEGKVDNLSRDSNRDCTNELSNSCKTRDDFLGQVDVPLYPLPTENPRLERPYTFKDFVLHPRSHKSRVK 491 - 560 GYLRLKMTYLPKTSGSEDDNAEQAEELEPGWVVLDQPDAACHLQQQQEPSPLPPGWEERQDILGRTYYVN 561 - 630 HESRRTQWKRPTPQDNLTDAENGNIQLQAQRAFTTRRQISEETESVDNRESSENWEIIREDEATMYSNQA 631 - 700 FPSPPPSSNLDVPTHLAEELNARLTIFGNSAVSQPASSSNHSSRRGSLQAYTFEEQPTLPVLLPTSSGLP 701 - 770 PGWEEKQDERGRSYYVDHNSRTTTWTKPTVQATVETSQLTSSQSSAGPQSQASTSDSGQQVTQPSEIEQG 771 - 840 FLPKGWEVRHAPNGRPFFIDHNTKTTTWEDPRLKIPAHLRGKTSLDTSNDLGPLPPGWEERTHTDGRIFY 841 - 910 INHNIKRTQWEDPRLENVAITGPAVPYSRDYKRKYEFFRRKLKKQNDIPNKFEMKLRRATVLEDSYRRIM 911 - 980 GVKRADFLKARLWIEFDGEKGLDYGGVAREWFFLISKEMFNPYYGLFEYSATDNYTLQINPNSGLCNEDH 981 - 1050 LSYFKFIGRVAGMAVYHGKLLDGFFIRPFYKMMLHKPITLHDMESVDSEYYNSLRWILENDPTELDLRFI 1051 - 1120 IDEELFGQTHQHELKNGGSEIVVTNKNKKEYIYLVIQWRFVNRIQKQMAAFKEGFFELIPQDLIKIFDEN 1121 - 1190 ELELLMCGLGDVDVNDWREHTKYKNGYSANHQVIQWFWKAVLMMDSEKRIRLLQFVTGTSRVPMNGFAEL 1191 - 1260 YGSNGPQSFTVEQWGTPEKLPRAHTCFNRLDLPPYESFEELWDKLQMAIENTQGFDGVD 1261 - 1319 //
