| 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
| Disease | Target Count |
|---|---|
| Keloid | 34 |
| Myocardial Ischemia | 169 |
| Stevens-Johnson syndrome | 91 |
| Disease | Target Count | P-value |
|---|---|---|
| glioblastoma | 5572 | 7.06164326573647E-8 |
| pilocytic astrocytoma | 3086 | 5.05361591262353E-7 |
| pediatric high grade glioma | 2712 | 8.91102484980052E-7 |
| lung carcinoma | 2844 | 5.18925992187946E-6 |
| lung cancer | 4473 | 0.011852265118106 |
| acute myeloid leukemia | 785 | 0.0412136906670177 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Skin disease | 65 | 0.0 | 2.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Liddle syndrome | 14 | 5.98 | 3.0 |
| Spinocerebellar ataxia type 31 | 7 | 4.758 | 2.4 |
| Pseudohypoaldosteronism | 22 | 3.536 | 1.8 |
| Cancer | 2346 | 3.156 | 1.6 |
| Hypertension | 293 | 3.048 | 1.5 |
| Disease | log2 FC | p |
|---|---|---|
| glioblastoma | 1.500 | 0.000 |
| lung cancer | -1.200 | 0.012 |
| pediatric high grade glioma | 1.400 | 0.000 |
| pilocytic astrocytoma | 1.800 | 0.000 |
| lung carcinoma | -1.200 | 0.000 |
| acute myeloid leukemia | -1.300 | 0.041 |
| Species | Source |
|---|---|
| Macaque | OMA EggNOG Inparanoid |
| Mouse | OMA EggNOG Inparanoid |
| Rat | OMA Inparanoid |
| Dog | EggNOG Inparanoid |
| Opossum | EggNOG Inparanoid |
| Platypus | OMA EggNOG Inparanoid |
| Chicken | OMA Inparanoid |
| Xenopus | OMA EggNOG Inparanoid |
| PMID | Text |
|---|---|
| 26854353 | LRAD3 is a component of pathways that function effectively to modulate Itch and Nedd4 auto-ubiquitination and levels. |
| 26685112 | These results show that the binding of the hNedd4-1 WW3* domain to alpha-hENaC is coupled to the folding equilibrium |
| 26503960 | Elevated NEDD4 is implicated as the responsible ubiquitin E3 ligase for HSF1 degradation through ubiquitin-proteasome system. Aberrant HSF1 degradation is a key neurodegenerative mechanism underlying alpha-synucleinopathy. |
| 26296893 | HUWE1 and NEDD4-1 are two E3 ligases that are fundamental enzymes in the post-translational regulation of ABCG1 and ABCG4 protein levels and cellular cholesterol export activity |
| 26263374 | we demonstrate that the E3 ubiquitin ligase NEDD4 ubiquitinates IFITM3 in cells and in vitro. |
| 26193427 | Study identifies NEDD4 as a putative oncogene in endometrial cancer that may augment activation of the IGF-1R/PI3K/Akt signaling pathway. |
| 26037357 | rs3088077, rs7162435 and rs2303579 of the NEDD4 gene are associated with schizophrenia. |
| 26006083 | Data show that human ABCB1 is a substrate for human NEDD4-1 and identified 8 lysine residues that were ubiquitinated by NEDD4-1. |
| 25883222 | Data show that silencing of PMEPA1 protein facilitates the growth of prostate cancer cells and modulates androgen receptor (AR) through NEDD4 ubiquitin protein ligase and PTEN protein. |
| 25879670 | Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity. |
| More... |
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 //
| PMID | Year | Title |
|---|---|---|
| 26854353 | 2016 | Regulation of Itch and Nedd4 E3 Ligase Activity and Degradation by LRAD3. |
| 26685112 | 2016 | The Nedd4-1 WW Domain Recognizes the PY Motif Peptide through Coupled Folding and Binding Equilibria. |
| 26503960 | 2016 | NEDD4-mediated HSF1 degradation underlies ?-synucleinopathy. |
| 26296893 | 2015 | The E3 ubiquitin ligases, HUWE1 and NEDD4-1, are involved in the post-translational regulation of the ABCG1 and ABCG4 lipid transporters. |
| 26263374 | 2015 | E3 Ubiquitin Ligase NEDD4 Promotes Influenza Virus Infection by Decreasing Levels of the Antiviral Protein IFITM3. |
| 26193427 | 2015 | NEDD4 ubiquitin ligase is a putative oncogene in endometrial cancer that activates IGF-1R/PI3K/Akt signaling. |
| 26037357 | 2015 | [Association of NEDD4 gene polymorphisms with schizophrenia and its clinical characteristics in Chinese Han population]. |
| 26006083 | 2015 | The multidrug resistance pump ABCB1 is a substrate for the ubiquitin ligase NEDD4-1. |
| 25883222 | 2015 | Silencing of PMEPA1 accelerates the growth of prostate cancer cells through AR, NEDD4 and PTEN. |
| 25879670 | 2015 | Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity. |
| More... |
