Product Details

Purity

Greater than 90% as determined by SDS-PAGE.

Target Names

NEDD4L

Uniprot No.

Q96PU5

Research Area

Cell Biology

Species

Homo sapiens (Human)

Source

E.coli

Expression Region

2-975aa

Target Protein Sequence

ATGLGEPVYGLSEDEGESRILRVKVVSGIDLAKKDIFGASDPYVKLSLYVADENRELALVQTKTIKKTLNPKWNEEFYFRVNPSNHRLLFEVFDENRLTRDDFLGQVDVPLSHLPTEDPTMERPYTFKDFLLRPRSHKSRVKGFLRLKMAYMPKNGGQDEENSDQRDDMEHGWEVVDSNDSASQHQEELPPPPLPPGWEEKVDNLGRTYYVNHNNRTTQWHRPSLMDVSSESDNNIRQINQEAAHRRFRSRRHISEDLEPEPSEGGDVPEPWETISEEVNIAGDSLGLALPPPPASPGSRTSPQELSEELSRRLQITPDSNGEQFSSLIQREPSSRLRSCSVTDAVAEQGHLPPPSAPAGRARSSTVTGGEEPTPSVAYVHTTPGLPSGWEERKDAKGRTYYVNHNNRTTTWTRPIMQLAEDGASGSATNSNNHLIEPQIRRPRSLSSPTVTLSAPLEGAKDSPVRRAVKDTLSNPQSPQPSPYNSPKPQHKVTQSFLPPGWEMRIAPNGRPFFIDHNTKTTTWEDPRLKFPVHMRSKTSLNPNDLGPLPPGWEERIHLDGRTFYIDHNSKITQWEDPRLQNPAITGPAVPYSREFKQKYDYFRKKLKKPADIPNRFEMKLHRNNIFEESYRRIMSVKRPDVLKARLWIEFESEKGLDYGGVAREWFFLLSKEMFNPYYGLFEYSATDNYTLQINPNSGLCNEDHLSYFTFIGRVAGLAVFHGKLLDGFFIRPFYKMMLGKQITLNDMESVDSEYYNSLKWILENDPTELDLMFCIDEENFGQTYQVDLKPNGSEIMVTNENKREYIDLVIQWRFVNRVQKQMNAFLEGFTELLPIDLIKIFDENELELLMCGLGDVDVNDWRQHSIYKNGYCPNHPVIQWFWKAVLLMDAEKRIRLLQFVTGTSRVPMNGFAELYGSNGPQLFTIEQWGSPEKLPRAHTCFNRLDLPPYETFEDLREKLLMAVENAQGFEGVD
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.

Mol. Weight

138.5 kDa

Protein Length

Full Length of Mature Protein

Tag Info

N-terminal GST-tagged

Form

Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.

Buffer

If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose.

Reconstitution

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

Shelf Life

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Lead Time

3-7 business days

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Datasheet & COA

Please contact us to get it.

Description

The expression region of this recombinant Human NEDD4L covers amino acids 2-975. The theoretical molecular weight of the NEDD4L protein is 138.5 kDa. Expression of this NEDD4L protein is conducted in e.coli. The NEDD4L coding gene included the N-terminal GST tag, which simplifies the detection and purification processes of the recombinant NEDD4L protein in following stages of expression and purification.

The human E3 ubiquitin-protein ligase NEDD4-like (NEDD4L) is a member of the NEDD4 family of HECT-type ubiquitin ligases. NEDD4L plays a key role in the regulation of protein degradation through the ubiquitin-proteasome system. It catalyzes the transfer of ubiquitin molecules onto substrate proteins, leading to their tagging for degradation. NEDD4L has been implicated in various cellular processes, including the control of cell growth, proliferation, and membrane trafficking. It interacts with a diverse array of substrates, including membrane proteins and signaling molecules, contributing to the regulation of multiple cellular pathways. NEDD4L's involvement in the ubiquitin-mediated protein degradation pathway makes it a crucial player in maintaining cellular homeostasis and responding to various physiological signals. Understanding NEDD4L's functions is essential for unraveling its roles in normal cellular processes and its potential implications in diseases.

Target Background

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.

Gene References into Functions

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
ULK1 phosphorylation at 3 different sites on the same ULK1 target region for NEDD4L is preparatory for its ubiquitylation and subsequent degradation. PMID: 28820317
WW3 and WW4 domains of Nedd4-2 are critical for its association with and modulation of the transporter. PMID: 28572241
study demonstrated significant genetic interaction on Na intake with child obesity by salt-sensitive genes variations, NEDD4L and CYP11beta2 PMID: 28017963
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
evidence implicating E3 ubiquitin ligase NEDD4L in the pathogeny of periventricular nodular heterotopia PMID: 27694961
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
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
both Nedd4-1 and Nedd4-2 are important regulators for hOAT1 ubiquitination, expression, and function PMID: 26823285
USP36 actions extend beyond TrkA because the presence of USP36 interferes with Nedd4-2-dependent Kv7.2/3 channel regulation. PMID: 27445338
NEDD4L negatively regulates PIK3CA protein levels via ubiquitination and is required for the maintenance of PI3K-AKT signaling pathway. PMID: 27339899
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
the regulation of Nedd4L protein expression may play a role in the development of ovarian cancers. PMID: 26554540
Propose regulation of placental SNAT2/LAT1 ubiquitination by mTORC1 and Nedd4-2. PMID: 26608079
Overexpression of Nedd4-2 enhanced hOAT4 ubiquitination, and inhibited hOAT4 transport activity. PMID: 26740304
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
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
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
Proteomics analysis of EV71-infected cells reveals the involvement of host protein NEDD4L in EV71 replication. PMID: 25785312
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
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
Genetic variation in NEDD4L may have sex-dependent effects in the development of essential hypertension in Han Chinese PMID: 24047422
NEDD4L may play a tumor suppressive role in colorectal cancer PMID: 24312311
glucocorticoid stimulation therefore appears to allow cAMP-dependent control of Na(+) absorption by facilitating the effects of PKA upon the Nedd4-2 PMID: 24657276
NEDD4L-rs12606138 and rs8094327 are risk factors for dyslexia in a German cohort. PMID: 24373531
Human NHE3, but not non-primates NHE3s, is ubiquitinated by Nedd4-2. PMID: 24831004
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
rs2288775 was significantly associated with metabolic syndrome x in female Kazakh in China. PMID: 24446284
Low NEDD4L expression is associated with non-small cell lung cancer. PMID: 23812770
Nedd4-2 plays an important role in the regulation of HCN1 trafficking and may compete with TRIP8b(1a-4) in this process PMID: 24451387
Nedd4L expression may be increased to facilitate tumour growth in many melanomas. PMID: 24456330
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
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
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
WNK4 inhibits ENaC channel activity independently of Nedd4-2-mediated ENaC ubiquitination. PMID: 23594824
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
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
Our results suggest for the first time that negative Nedd4L expression is strongly related to the invasion and metastasis of gastric cancer PMID: 21909941
NEDD4L is a negative feedback regulator of Wnt signaling. PMID: 23396981
CNP12587 region, overlapping NEDD4L, may have a role in underlying height variation in Chinese females PMID: 22957059
Nedd4-2 does not ubiquitinate and thereby regulate wt-CFTR in human airway epithelial cells. PMID: 22904170
hERG expression in the plasma membrane is regulated by Cav3 via Nedd4-2 PMID: 22879586
GLT-1 endocytosis is independent of its phosphorylation and that Nedd4-2 mediates PKC-dependent down-regulation of the transporter. PMID: 22505712
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
Nedd4-2 mediated ubiquitination regulates the cell surface expression of CHT1 in HEK293 cells. PMID: 22361880
expression of Nedd4L is down-regulated in human gliomas. PMID: 22217575
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
stimulated NCC ubiquitylation at the surface of transfected HEK293 cells PMID: 21852580
D-C-G-G haplotype of NEDD4L but not rs4149601 polymorphism was linked with hypertension in Kazakh. PMID: 21176637
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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Involvement in disease

Periventricular nodular heterotopia 7 (PVNH7)

Subcellular Location

Cytoplasm. Golgi apparatus. Endosome, multivesicular body. Note=May be recruited to exosomes by NDFIP1.

Tissue Specificity

Ubiquitously expressed, with highest levels in prostate, pancreas and kidney. Expressed in melanocytes.

Database Links

HGNC: 7728

OMIM: 606384

KEGG: hsa:23327

STRING: 9606.ENSP00000383199

UniGene: Hs.185677

Code	CSB-EP850411HU(A4)
Abbreviation	Recombinant Human NEDD4L protein
MSDS	MSDS Datasheet
Size	$306
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Image	(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Recombinant Human E3 ubiquitin-protein ligase NEDD4-like (NEDD4L)

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