Recombinant Human JAK1 (d966-989) Protein

Beta LifeScience SKU/CAT #: BL-0439SG

Recombinant Human JAK1 (d966-989) Protein

Beta LifeScience SKU/CAT #: BL-0439SG
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Product Overview

Tag GST
Host Species Human
Accession NM_002227
Synonym JAK1A, JAK1B
Background JAK1 is a member of protein-tyrosine kinases (PTK) characterized by the presence of a second phosphotransferase-related domain immediately N-terminal to the PTK domain. JAK1 bears all the hallmarks of a protein kinase, although its structure differs significantly from that of the PTK and threonine/serine kinase family members. JAK1 is a large, widely expressed membrane-associated phosphoprotein that is involved in the interferon-alpha/beta and -gamma signal transduction pathways (1). JAK1 plays an essential and nonredundant role in promoting biologic responses induced by a select subset of cytokine receptors, including those in which JAK utilization is thought to be nonspecific(2).
Description Recombinant human JAK1 (d966-989) (438-end) was produced by baculovirus in Sf9 insect cells, fused with a GST tag at N-terminus. This protein is purified with our unique purification methods.
Source Sf9 insect cells
AA Sequence 438a.a.-end
Molecular Weight ~105 kDa
Purity For specific purity information on a given lot, see related COA.
Endotoxin < 1.0 EU per μg of the protein as determined by the LAL method
Bioactivity Active
Formulation Recombinant protein is supplied in 50mM Tris-HCl, pH 7.5, 50mM NaCl, 10mM Glutathione, 0.25mM DTT, 0.1mM EDTA, 0.1mM PMSF and 25% glycerol.
Stability The recombinant protein is stable for up to 12 months at -70°C
Usage For Research Use Only
Storage Recombinant Human JAK1 (d966-989) Protein should be stored should be stored at < -70°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

Target Details

Target Function Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor as well as interleukin (IL)-10 receptor. Directly phosphorylates STAT but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors.
Subcellular Location Endomembrane system; Peripheral membrane protein. Note=Wholly intracellular, possibly membrane associated.
Protein Families Protein kinase superfamily, Tyr protein kinase family, JAK subfamily
Database References
Tissue Specificity Expressed at higher levels in primary colon tumors than in normal colon tissue. The expression level in metastatic colon tumors is comparable to the expression level in normal colon tissue.

Gene Functions References

  1. Low-dose radiation decreases tumor progression via the inhibition of the JAK1/STAT3 signaling axis in breast cancer cell lines and in a mouse xenograft model. PMID: 28240233
  2. Case Report: breast implant-associated anaplastic large cell lymphoma with dual JAK1/STAT3 mutations. PMID: 29637270
  3. A small drug acting as a JAK1/2 inhibitor may also counteract the repressing effects of IL-6. PMID: 29162613
  4. These findings clarify JAK1 signalling mechanisms and demonstrate a critical function of JAK1 in protection against mycobacterial infection and possibly the immunological surveillance of cancer. PMID: 28008925
  5. In the Title. PMID: 27554814
  6. Study concluded that JAK1 plays a role in the pathogenesis of both vitiligo and psoriasis based on its upregulated level before treatment and downregulated level after treatment. PMID: 29127481
  7. High JAK1 expression is associated with metastasis of pancreatic ductal adenocarcinoma. PMID: 28677798
  8. IL6 family cytokine oncostatin-M (OSM) induced a switch to the EMT phenotype and protected cells from targeted drug-induced apoptosis in OSM receptors (OSMRs)/JAK1/STAT3-dependent manner PMID: 28729401
  9. Amorfrutin A also inhibited activation of the upstream kinases Janus-activated kinase 1 (JAK1), JAK2 and Src signaling pathways. PMID: 28879797
  10. Jak1 is required for the survival of anaplastic large cell lymphoma.Jak1 mutations in anaplastic large cell lymphoma. PMID: 28356514
  11. The good consonance between the docking results and CoMFA/CoMSIA contour maps provides helpful clues about the reasonable modification of molecules in order to design more efficient JAK 1 inhibitors. The developed models are expected to provide some directives for further synthesis of highly effective JAK 1 inhibitors. PMID: 28537140
  12. Here we report a molecular mechanism by which JAK1 contributes to the malignant phenotype of activated B-cell diffuse large B-cell lymphoma (ABC DLBCL). Epigenetic regulation by JAK1 plays a prominent role in the gene expression program of ABC DLBCL cells by phosphorylating chromatin on H3Y41. The chromatin of nearly 3,000 genes had JAK1-dependent H3Y41 phosphorylation marks and required JAK1 for their expression. PMID: 27799566
  13. miR-30e has a critical role in the suppression of hepatocellular carcinoma (HCC) and presents a novel mechanism of miRNA-mediated JAK1 expression in cancer cells that might be a good prognostic marker for survival of HCC patients. PMID: 28560434
  14. We demonstrate that impaired recruitment of CD11b(+) myeloid cells with a JAK1/2 inhibitor inhibits glioma progression in vivo and prolongs survival in a murine glioma model. PMID: 28039266
  15. Whole-exome sequencing on patients with acute lymphoblastic leukemia (ALL) and discovered a somatic JAK1 S646P mutation. Functional studies demonstrated that only JAK1 S646P mutation could activate multiple signaling pathways, drive cytokine-independent cell growth, and promote proliferation of malignant cells in nude mice. PMID: 28410228
  16. we have identified acquired activating mutations in JAK1 and STAT3 in two cases of effusion-limited BIA-ALCL and identified a possible contribution to disease development from a germline JAK3 variant. PMID: 27198716
  17. JAK1 mutations are highly frequent in microsatellite unstable endometrial cancer, not associated with survival, but are associated with impaired upregulation of LMP7 and HLA class I and may therefore facilitate immune escape PMID: 27213585
  18. We found that a significant higher gastric cancer risk was associated with IL-6 rs2069837G variant genotypes and JAK1 rs2230587A variant genotypes PMID: 27049718
  19. 6-Hydroxy-3-O-methyl-kaempferol 6-O-glucopyranoside potentiated the inhibitory effect of IFN-alpha on hepatocellular carcinoma cell proliferation through activation of the JAK/STAT signaling pathway by inhibiting SOCS3 expression. PMID: 29031523
  20. JAK1 frameshifts are loss of function alterations that represent a potential pan-cancer adaptation to immune responses against tumors with microsatellite instability PMID: 29121062
  21. Study provides evidence that JAK1/2 loss-of-function mutations are a genetic mechanism of lack of reactive PD-L1 expression and response to interferon gamma, leading to primary resistance to PD-1 blockade therapy. PMID: 27903500
  22. This study demonstrates that the nuclear import of JAK1 is essential for the optimal fitness of ABC DLBCL cells. PMID: 28031410
  23. JAK1 rs11576173 and rs1497056 genotypes were significantly related to severe necroinflammatory activity (NIA) grade of chronic hepatitis C patients. PMID: 28704535
  24. Multiple myeloma cells over express JAK1/2 and suggest combined chemotherapy with ruxolitinib, bortezomib and lenalidomide to inhibit JAK/STAT pathway. PMID: 28645562
  25. Mechanistic investigations reveal that AJUBA specifically binds the FERM domain of JAK1 to dissociate JAK1 from the IFNgamma recepter, resulting in an inhibition of STAT1 phosporylation and concomitantly its nuclear translocation. Clinically, the level of AJUBA in CRC specimens is negatively correlated with the levels of IFIT2 and pSTAT1 PMID: 27893714
  26. Multilevel genomic analyses of microsatellite instability+ colorectal cancer revealed molecular heterogeneity with clinical relevance, including tumor immunogenicity and a favorable patient outcome associated with JAK1 mutations and the transcriptomic subgroup CMS1 PMID: 28539123
  27. a causal relationship between MLH1-deficiency and incidence of oncogenic point mutations in tyrosine kinases driving cell transformation and acquired resistance to kinase-targeted cancer therapies, is reported. PMID: 27436342
  28. Data show that moringin (GMG-ITC) had a limited inhibitory effect on IFNalpha-induced STAT1 and STAT2 activity, indicating differentially targeting JAK/STAT signaling pathways. PMID: 27304884
  29. our studies highlight Jak1 as the first identified substrate for USP6, and they offer a mechanistic rationale for the clinical investigation of Jak and STAT3 inhibitors as therapeutics for the treatment of bone and soft tissue tumors along with other neoplasms driven by USP6 overexpression PMID: 27440725
  30. In this structure, the receptor peptide forms an 85-A-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. PMID: 27725180
  31. Results reveal the structure of box1 from class II cytokine receptors IFNLR1 and IL10RA bound to the FERM-SH2 domain of human JAK1, identifying a consensus motif for JAK1 interaction. PMID: 27133025
  32. study demonstrated that miR-9 could inhibit activation of the NLRP3 inflammasome and attenuate atherosclerosis-related inflammation, likely through the JAK1/STAT1 signaling pathway. Therefore, miR-9 may serve as a potential therapeutic target for atherosclerosis. PMID: 28334721
  33. miR-340 suppressed HCC cell proliferation and invasion by regulating the JAK1/STAT3 pathway PMID: 27998770
  34. this study identifies a psoriasis-protective JAK1 haplotype in the Korean population PMID: 27774581
  35. Data show that tight junction protein 1 (TJP1) suppressed expression of the catalytically proteasome subunits LMP7 and LMP2, decreased proteasome activity, and enhanced proteasome inhibitor sensitivity in vitro and in vivo through suppression of EGFR/JAK1/STAT3 signaling. PMID: 27132469
  36. EGFR Del 19 may promote Fn14 and JAK1/STAT1 expression in NSCLC. PMID: 27350337
  37. Piperlongumine reduced the phosphorylation of Janus kinase (JAK)1, JAK2 and signal transducer and activator of transcription (STAT)3 in a concentrationdependent manner PMID: 27053336
  38. JAK1 rs310241 C-related genotype and allele are involved in AR susceptibility, making them potentially useful genetic biomarkers for allergic rhinitis susceptibility in the Chinese Han population. PMID: 27007833
  39. Data show that astaxanthin functions as a potent inhibitor of A549 lung cancer cell growth by targeting Janus kinase 1 a(JAK1)/STAT3 transcription factor (STAT3) signaling pathway. PMID: 27371847
  40. Genetic Variation in the JAK1 gene is associated with distal Colonic Disease, Stricturing Disease Behavior. PMID: 26937622
  41. Activating JAK1 mutation may predict the sensitivity of JAK-STAT inhibition in hepatocellular carcinoma. PMID: 26701727
  42. Foot-and-mouth disease virus VP3 interacted with JAK1/2, degraded JAK1, and inhibited the tyrosine phosphorylation, dimerization and nuclear accumulation of STAT1. PMID: 26901336
  43. Data suggest that targeting both TGF-beta and Janus kinase 1 (JAK1) signaling could be explored therapeutically in pancreatic ductal adenocarcinomas (PDACs) patients whose cancers exhibit an angiogenesis gene signature. PMID: 26586478
  44. When association tests were applied to data from the Diabetes Heart Study, it found exome variants of POMGNT1 and JAK1 genes were associated with type 2 diabetes. PMID: 26783077
  45. Studies indicate that Janus kinase 1 (JAK1) inhibition leads to depression in inflammatory cytokine expression associated with MF-related constitutional symptoms. PMID: 25586607
  46. Mutations leading to constitutive active gp130/JAK1/STAT3 pathway. PMID: 26188635
  47. Increased expression of SgK223 occurs in PDAC, and overexpression of SgK223 in pancreatic ductal epithelial cells promotes acquisition of a migratory and invasive phenotype through enhanced JAK1/Stat3 signaling PMID: 26215634
  48. Data show that IFN-lambda induced a faster but shorter expression of suppressor of cytokine signaling 1 (SOCS1) which inhibited Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway and phosphorylation. PMID: 26193702
  49. Shp-2 contributes to the control of respiratory syncytial virus replication and progeny production in pulmonary alveolar epithelial cells by interfering with IFN-alpha-induced Jak/Stat1 pathway activation PMID: 26119280
  50. Data show that JAK/STAT signaling inhibition is potentiated by Bcl-xL (B-cell lymphoma-extra large) blockade in interleukin 2 (IL-2) dependent adult T-cell leukemia cells. PMID: 26396258

FAQs

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

To learn more about how to properly dissolve the lyophilized recombinant protein, please visit Lyophilization FAQs.

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