Recombinant Human E3 Ubiquitin-Protein Ligase Nedd4-Like (NEDD4L) Protein (GST)

Beta LifeScience SKU/CAT #: BLC-00921P
Greater than 90% as determined by SDS-PAGE.
Greater than 90% as determined by SDS-PAGE.

Recombinant Human E3 Ubiquitin-Protein Ligase Nedd4-Like (NEDD4L) Protein (GST)

Beta LifeScience SKU/CAT #: BLC-00921P
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Product Overview

Description Recombinant Human E3 Ubiquitin-Protein Ligase Nedd4-Like (NEDD4L) Protein (GST) is produced by our E.coli expression system. This is a full length protein.
Purity Greater than 90% as determined by SDS-PAGE.
Uniprotkb Q96PU5
Target Symbol NEDD4L
Species Homo sapiens (Human)
Expression System E.coli
Tag N-GST
Target Protein Sequence ATGLGEPVYGLSEDEGESRILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYMPKNGGQDEENSDQRDDMEHGWEVVDSNDSASQHQEELPPPPLPPGWEEKVDNLGRTYYVNHNNRTTQWHRPSLMDVSSESDNNIRQINQEAAHRRFRSRRHISEDLEPEPSEGGDVPEPWETISEEVNIAGDSLGLALPPPPASPGSRTSPQELSEELSRRLQITPDSNGEQFSSLIQREPSSRLRSCSVTDAVAEQGHLPPPSAPAGRARSSTVTGGEEPTPSVAYVHTTPGLPSGWEERKDAKGRTYYVNHNNRTTTWTRPIMQLAEDGASGSATNSNNHLIEPQIRRPRSLSSPTVTLSAPLEGAKDSPVRRAVKDTLSNPQSPQPSPYNSPKPQHKVTQSFLPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRLKFPVHMRSKTSLNPNDLGPLPPGWEERIHLDGRTFYIDHNSKITQWEDPRLQNPAITGPAVPYSREFKQKYDYFRKKLKKPADIPNRFEMKLHRNNIFEESYRRIMSVKRPDVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLCNEDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWILENDPTELDLMFCIDEENFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSNGPQLFTIEQWGSPEKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFEGVD
Expression Range 2-975aa
Protein Length Full Length of Mature Protein
Mol. Weight 138.5 kDa
Research Area Cell Biology
Form Liquid or Lyophilized powder
Buffer Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage 1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target Function 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. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5. Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1. Plays a role in dendrite formation by melanocytes. Involved in the regulation of TOR signaling. Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF.
Subcellular Location Cytoplasm. Golgi apparatus. Endosome, multivesicular body. Note=May be recruited to exosomes by NDFIP1.
Database References
Associated Diseases Periventricular nodular heterotopia 7 (PVNH7)
Tissue Specificity Ubiquitously expressed, with highest levels in prostate, pancreas and kidney. Expressed in melanocytes.

Gene Functions References

  1. Sgk1 stimulated OAT3 transport activity by interfering with the inhibitory effect of Nedd4-2 on the transporter. This study provides important insights into how OAT3-mediated drug elimination is regulated in vivo. PMID: 28608480
  2. ULK1 phosphorylation at 3 different sites on the same ULK1 target region for NEDD4L is preparatory for its ubiquitylation and subsequent degradation. PMID: 28820317
  3. WW3 and WW4 domains of Nedd4-2 are critical for its association with and modulation of the transporter. PMID: 28572241
  4. study demonstrated significant genetic interaction on Na intake with child obesity by salt-sensitive genes variations, NEDD4L and CYP11beta2 PMID: 28017963
  5. Collectively, Nedd4L plays a tumor suppressive role in HCC, possibly through triggering MAPK/ERK-mediated apoptosis, and Nedd4L downregulation may be a potential prognostic biomarker as well as a therapeutic target for HCC. PMID: 29175326
  6. evidence implicating E3 ubiquitin ligase NEDD4L in the pathogeny of periventricular nodular heterotopia PMID: 27694961
  7. This study demonstrated that it is possible to downregulate Kv1.3 channel density through activation of an E3 ubiquitin ligase and that inhibition of the protease pathway or mutation of the Nedd4-2 catalytic site prevents Kv1.3 modulation. PMID: 27146988
  8. These findings provide evidence that Nedd4-2 is up-regulated in response to endoplasmic reticulum stress by the spliced form of X-box binding protein 1 and that this is important in the induction of an appropriate autophagic response. PMID: 27022162
  9. both Nedd4-1 and Nedd4-2 are important regulators for hOAT1 ubiquitination, expression, and function PMID: 26823285
  10. USP36 actions extend beyond TrkA because the presence of USP36 interferes with Nedd4-2-dependent Kv7.2/3 channel regulation. PMID: 27445338
  11. NEDD4L negatively regulates PIK3CA protein levels via ubiquitination and is required for the maintenance of PI3K-AKT signaling pathway. PMID: 27339899
  12. overexpression of miR-93 in lung cancer cells promoted TGF-b-induced EMT through downregulation of NEDD4L. The analysis of publicly available gene expression array datasets indicates that low NEDD4L expression correlates with poor outcomes among patients with lung cancer, further supporting the oncogenic role of miR-93 in lung tumorigenesis and metastasis. PMID: 26581907
  13. the regulation of Nedd4L protein expression may play a role in the development of ovarian cancers. PMID: 26554540
  14. Propose regulation of placental SNAT2/LAT1 ubiquitination by mTORC1 and Nedd4-2. PMID: 26608079
  15. Overexpression of Nedd4-2 enhanced hOAT4 ubiquitination, and inhibited hOAT4 transport activity. PMID: 26740304
  16. Our results suggest that three screened NEDD4-2 variants do not play a leading role in the pathogenesis of photosensitive epilepsy in the Turkish population. PMID: 25542253
  17. The mechanisms of activation and degradation of the NEDD4L:the transition from the closed to the active form is regulated by a competition of inositol 1,4,5-trisphosphate and Ca2+. PMID: 25295397
  18. Data show that membrane protein Ndfip1 recruits E3 ubiquitin (Ub) ligase Nedd4-2 to the Golgi to target ether-a-go-go-related gene (hERG) channel for degradation while membrane protein Ndfip2 also mediates Nedd4-2 interaction with hERG in the Golgi. PMID: 26363003
  19. Proteomics analysis of EV71-infected cells reveals the involvement of host protein NEDD4L in EV71 replication. PMID: 25785312
  20. DDB2 can bind to the promoter region of NEDD4L and recruit enhancer of zeste homolog 2 histone methyltransferase to repress NEDD4L transcription by enhancing histone H3 lysine 27 trimethylation at the NEDD4L promoter. PMID: 26130719
  21. These results suggested that the functional variant of NEDD4L, rs4149601, may be associated with obesity and related phenotypes, and further genetic and functional studies are required to understand its role in the manifestation of obesity. PMID: 23549273
  22. Genetic variation in NEDD4L may have sex-dependent effects in the development of essential hypertension in Han Chinese PMID: 24047422
  23. NEDD4L may play a tumor suppressive role in colorectal cancer PMID: 24312311
  24. glucocorticoid stimulation therefore appears to allow cAMP-dependent control of Na(+) absorption by facilitating the effects of PKA upon the Nedd4-2 PMID: 24657276
  25. NEDD4L-rs12606138 and rs8094327 are risk factors for dyslexia in a German cohort. PMID: 24373531
  26. Human NHE3, but not non-primates NHE3s, is ubiquitinated by Nedd4-2. PMID: 24831004
  27. The NEDD4L salt sensitivity-associated genotype was associated with higher blood pressure, which may translate into increased risk for CVD morbidity and mortality. PMID: 24284497
  28. rs2288775 was significantly associated with metabolic syndrome x in female Kazakh in China. PMID: 24446284
  29. Low NEDD4L expression is associated with non-small cell lung cancer. PMID: 23812770
  30. Nedd4-2 plays an important role in the regulation of HCN1 trafficking and may compete with TRIP8b(1a-4) in this process PMID: 24451387
  31. Nedd4L expression may be increased to facilitate tumour growth in many melanomas. PMID: 24456330
  32. PI3K-SGK1 pathway stabilizes Kv7.1 surface expression by inhibiting Nedd4-2-dependent endocytosis and thereby demonstrates that Nedd4-2 is a key regulator of Kv7.1 localization and turnover in epithelial cells. PMID: 24214981
  33. Data indicate that Rab4 regulates ether-a-go-go-related gene (hERG) channel density via neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2). PMID: 23792956
  34. Understanding of the contribution of Nedd4 and Nedd4-2 in regulating key functions in the brain is shedding new light on the ubiquitination signal not only in orchestrating degradation events but also in protein trafficking PMID: 23262292
  35. WNK4 inhibits ENaC channel activity independently of Nedd4-2-mediated ENaC ubiquitination. PMID: 23594824
  36. NEDD4L rs4149601, rs292449 and rs75982813 may be predictors for blood pressure response to hydrochlorothiazide in whites, and NEDD4L rs4149601 may be a predictor for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide PMID: 23353631
  37. SGK1,3 enhances the expression level of mature hERG channels by inhibiting Nedd4-2 as well as by promoting Rab11-mediated hERG recycling. PMID: 23589291
  38. Our results suggest for the first time that negative Nedd4L expression is strongly related to the invasion and metastasis of gastric cancer PMID: 21909941
  39. NEDD4L is a negative feedback regulator of Wnt signaling. PMID: 23396981
  40. CNP12587 region, overlapping NEDD4L, may have a role in underlying height variation in Chinese females PMID: 22957059
  41. Nedd4-2 does not ubiquitinate and thereby regulate wt-CFTR in human airway epithelial cells. PMID: 22904170
  42. hERG expression in the plasma membrane is regulated by Cav3 via Nedd4-2 PMID: 22879586
  43. GLT-1 endocytosis is independent of its phosphorylation and that Nedd4-2 mediates PKC-dependent down-regulation of the transporter. PMID: 22505712
  44. Three members of Nedd4 (neural-precursor-cell-expressed developmentally down-regulated)-like ubiquitin E3 ligases, Nedd4, Nedd4-2 and Itch were identified, as the ubiquitin E3 ligases for the long isoform of AMOT, AMOT/p130. PMID: 22385262
  45. Nedd4-2 mediated ubiquitination regulates the cell surface expression of CHT1 in HEK293 cells. PMID: 22361880
  46. expression of Nedd4L is down-regulated in human gliomas. PMID: 22217575
  47. Neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) regulation by 14-3-3 protein binding at canonical serum and glucocorticoid kinase 1 (SGK1) phosphorylation sites. PMID: 21900244
  48. stimulated NCC ubiquitylation at the surface of transfected HEK293 cells PMID: 21852580
  49. D-C-G-G haplotype of NEDD4L but not rs4149601 polymorphism was linked with hypertension in Kazakh. PMID: 21176637
  50. the data support the conclusion that Usp2-45 action on epithelial Na(+) channel is promoted by various interactions, including through binding to Nedd4-2 PMID: 21478478

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