Recombinant Human NLK Protein (His & GST Tag)
Beta LifeScience
SKU/CAT #: BLPSN-3529
Recombinant Human NLK Protein (His & GST Tag)
Beta LifeScience
SKU/CAT #: BLPSN-3529
Collections: Other recombinant proteins, Recombinant proteins
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Product Overview
Tag | His&GST |
Host Species | Human |
Accession | Q9UBE8 |
Background | Nemo-like kinase contains 1 protein kinase domain and belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family and MAP kinase subfamily. It also contains a TQE activation loop motif in which autophosphorylation of the threonine residue (Thr-298) is sufficient for kinase activation. As a serine/threonine-protein kinase, nemo-like kinase regulates a number of transcription factors with key roles in cell fate determination. It is a positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Activation of this pathway causes binding to and phosphorylation of the histone methyltransferase SETDB1. The NLK-SETDB1 complex subsequently interacts with PPARG, leading to methylation of PPARG target promoters at histone H3K9 and transcriptional silencing. The resulting loss of PPARG target gene transcription inhibits adipogenesis and promotes osteoblastogenesis in mesenchymal stem cells (MSCs). Nemo-like kinase also is a negative regulator of the canonical Wnt/beta-catenin signaling pathway. |
Description | A DNA sequence encoding the human NLK (Q9UBE8) (Val121-Glu527) was fused with the N-terminal His-tagged GST tag at the N-terminus. |
Source | Baculovirus-Insect Cells |
Predicted N Terminal | Met |
AA Sequence | Val121-Glu527 |
Molecular Weight | The recombinant human NLK /GST chimera consists of 644 a.a. and has a calculated molecular mass of 74.1 kDa. The recombinant protein migrates as an approximately 73 kDa band in SDS-PAGE under reducing conditions. |
Purity | >91% as determined by SDS-PAGE |
Endotoxin | < 1.0 EU per μg of the protein as determined by the LAL method |
Bioactivity | The specific activity was determined to be 3 nmol/min/mg using MBP as substrate. |
Formulation | Supplied as sterile 20mM Tris, 500mM NaCl, pH 8.0, 10% gly. |
Stability | The recombinant proteins are stable for up to 1 year from date of receipt at -70°C. |
Usage | For Research Use Only |
Storage | Store the protein under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles. |
Target Details
Target Function | Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination. Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2. Negative regulator of the canonical Wnt/beta-catenin signaling pathway. Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1. Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes. Negative regulator of the Notch signaling pathway. Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1. Negative regulator of the MYB family of transcription factors. Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP. Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself. Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1. Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members. Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner. |
Subcellular Location | Nucleus. Cytoplasm. |
Protein Families | Protein kinase superfamily, CMGC Ser/Thr protein kinase family, MAP kinase subfamily |
Database References |
Gene Functions References
- overexpression of miR-221 decreased LEF1 phosphorylation but increased the expression of MYCN via targeting of NLK and further regulated cell cycle, particularly in S-phase. This study provides a novel insight for miR-221 in the control of neuroblastoma cell proliferation and tumorigenesis, suggesting potentials of miR-221 as a prognosis marker and therapeutic target for patients with MYCN overexpressing neuroblastoma. PMID: 28003306
- NLK is a novel signaling molecule for proper lung development through the interconnection between epithelial and endothelial cells during lung morphogenesis PMID: 27035511
- Our results suggest that NLK inhibits transcriptional activation of Nurr1 gene by impeding CBP's role as a co-activator of NF-kappaB and CREB in prostate cancer. PMID: 27036119
- The expression of NLK was negatively correlated with TCF4 expression in lung cancers PMID: 26823848
- NLK overexpression is an independent prognostic factor in colorectal cancer and knockdown of NLK expression inhibits colorectal cancer progression and metastasis. PMID: 26269673
- Further experiments demonstrated that the overexpression of miR3623p resulted in decrease expression levels of nemo-like kinase PMID: 26647877
- NLK was involved in miR-92b-induced cell proliferation, and its protein level was obviously downregulated in the miR-92b-overexpressing xenograft tumors. PMID: 26503628
- Data show that metformin inhibits nemo like kinase (NLK) expression and might be a potential treatment strategy for non-small cell lung cancer (NSCLC). PMID: 26503334
- Down-regulation of NLK inhibited tumorigenesis and up-regulated the expression of cell cycle proteins in laryngeal cancer cells. PMID: 26252054
- In this review, we will make a summary on the comprehensive roles of NLK in the regulation of various cancers PMID: 26427665
- NLK was an identified miR-199a-3p target gene and functioned as a tumor suppressor gene in colorectal cancer. PMID: 24972723
- NLK overexpression is associated with poor overall survival in patients with hepatocellular carcinoma(HCC), it might be an independent poor prognostic marker for HCC. PMID: 26022162
- NLK phosphorylates Raptor on S863 to disrupt its interaction with the Rag GTPase, which is important for mTORC1 lysosomal recruitment. PMID: 26588989
- our work first demonstrated that miR-197 can confer drug resistance to Taxol, by regulating tumor suppressor, NLK expression in ovarian cancer cells. PMID: 25833695
- Data indicate that heat-shock protein 27 HSP27) binds to Nemo-like kinase (NLK) in the nucleus. PMID: 24816797
- NLK is an important p53 regulator that responds to DNA damage. NLK interacts with p53 and stabilizes p53 by blocking MDM2-mediated p53 ubiquitination and degradation. PMID: 24926618
- High nemo-like kinase expression is associated with drug resistance in laryngeal cancer. PMID: 24460265
- NLK is a negative regulator in cell proliferation of non-small-cell lung cancer by modulating the activity of Wnt/beta-catenin signaling. PMID: 23904219
- NLK functions as a pivotal negative regulator of NF-kappaB via disrupting the interaction of TAK1 with IKKbeta. PMID: 24721172
- The results suggest that NLK silencing by lentivirus-mediated RNA interference would be a potential therapeutic method to control oral squamous carcinoma growth. PMID: 23983589
- NLK suppressed proliferation, induced apoptosis and mediated c-Myb degradation in MCF-7 cells. PMID: 23935942
- Data indicate that overexpression of nemo-like kinase (NLK) is closely related to progression of gallbladder cancer (GBC), and NLK could be used as a potential prognostic marker for GBC patients. PMID: 23857283
- Reduced expression of NLK is associated with glioma. PMID: 23416699
- Our results suggested that NLK is a key regulator involved in proliferation and migration of GBC, and it could be used as a potential therapeutic target for gallbladder carcinoma cells. PMID: 22733362
- Single nucleotide polymorphisms in NLK is associated with ovarian cancer. PMID: 22253297
- expression suppressed in the development of ovarian cancer PMID: 22027747
- NLK induces apoptosis in glioma cells via activation of caspases; NLK may be a useful independent prognostic indicator for glioma. PMID: 21177110
- ZIPK may serve as a transcriptional regulator of canonical Wnt/beta-catenin signaling through interaction with NLK/TCF4. PMID: 21454679
- dimerization is an initial key event required for the functional activation of NLK PMID: 21118996
- NLK is aberrantly regulated in hepatocellular carcinoma and this process appears to involve the induction of CDK2 and cyclin D1 PMID: 20512928
- findings provide the first evidence that TAK1-NLK pathway is a novel regulator of FOXO1 PMID: 20061393
- NLK negatively regulates Notch-dependent transcriptional activation by phosphorylating Notch1ICD. Phosphorylated Notch1ICD is impaired in its ability to form a transcriptionally active ternary complex. PMID: 20118921
- threonine 9 (Thr9) and Serine 138 (Ser138) within the N-terminal Mad homology1 (MH1) domain of Smad4 could be phosphorylated by NLK PMID: 19690946
- The induction of wild-type NLK in DLD-1 human colon cancer cells caused suppression of cell growth whereas the kinase-negative mutant did not. PMID: 12901858
- Nemo-like kinase is activated by Wnt PMID: 14960582
- STAT3 enhances the efficiency of its own Ser-727 phosphorylation by acting as a scaffold for the TAK1-NLK kinases PMID: 15764709
- These results strongly suggest that unlike cytokine signaling, Tax-induced NFkappaB activation does not involve K63 polyubiquitination-mediated MAP3K activation. PMID: 17418100
- Fbxw7, the F-box protein of an SCF complex, targets c-Myb for degradation in a Wnt-1- and NLK-dependent manner. PMID: 18765672
- NLK expression is altered during prostate cancer progression and it is involved in regulation of AR signaling in these cells PMID: 19514049