Recombinant Human Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)

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Code CSB-EP019736HU
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Size $224
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Product Details

Purity
Greater than 90% as determined by SDS-PAGE.
Target Names
RIPK2
Uniprot No.
Research Area
Immunology
Alternative Names
CARD 3; CARD carrying kinase; CARD containing ICE associated kinase; CARD containing IL 1 beta ICE kinase; CARD containing IL1 beta ICE kinase; CARD containing interleukin 1 beta converting enzyme (ICE) associated kinase; CARD containing interleukin 1 beta converting enzyme associated kinase; CARD-containing IL-1 beta ICE-kinase; CARD-containing interleukin-1 beta-converting enzyme-associated kinase; CARD3; CARDIAK; CCK; CLARP kinase; GIG 30; GIG30; Growth inhibiting gene 30; Receptor interacting protein (RIP) like interacting caspase like apoptosis regulatory protein (CLARP) kinase; Receptor interacting protein 2 ; Receptor interacting serine threonine kinase 2; Receptor interacting serine/threonine protein kinase 2; Receptor-interacting protein 2; Receptor-interacting serine/threonine-protein kinase 2; RICK; RIP 2; RIP like interacting CLARP kinase; RIP-2; RIP-like-interacting CLARP kinase; RIPK 2; Ripk2; RIPK2_HUMAN; TNFRSF; Tyrosine-protein kinase RIPK2; UNQ277/PRO314/PRO34092
Species
Homo sapiens (Human)
Source
E.coli
Expression Region
1-540aa
Target Protein Sequence
MNGEAICSALPTIPYHKLADLRYLSRGASGTVSSARHADWRVQVAVKHLHIHTPLLDSERKDVLREAEILHKARFSYILPILGICNEPEFLGIVTEYMPNGSLNELLHRKTEYPDVAWPLRFRILHEIALGVNYLHNMTPPLLHHDLKTQNILLDNEFHVKIADFGLSKWRMMSLSQSRSSKSAPEGGTIIYMPPENYEPGQKSRASIKHDIYSYAVITWEVLSRKQPFEDVTNPLQIMYSVSQGHRPVINEESLPYDIPHRARMISLIESGWAQNPDERPSFLKCLIELEPVLRTFEEITFLEAVIQLKKTKLQSVSSAIHLCDKKKMELSLNIPVNHGPQEESCGSSQLHENSGSPETSRSLPAPQDNDFLSRKAQDCYFMKLHHCPGNHSWDSTISGSQRAAFCDHKTTPCSSAIINPLSTAGNSERLQPGIAQQWIQSKREDIVNQMTEACLNQSLDALLSRDLIMKEDYELVSTKPTRTSKVRQLLDTTDIQGEEFAKVIVQKLKDNKQMGLQPYPEILVVSRSPSLNLLQNKSM
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight
65.2kDa
Protein Length
Full Length
Tag Info
N-terminal 6xHis-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.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
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
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

Like all recombinant proteins, this Recombinant Human RIPK2 protein was encoded by recombinant DNA. The recombinant DNA was introduced to a plasmid in which the gene of RIPK2 was cloned downstream of a promoter region. When the plasmid was introduced to the cells of E.coli, the E.coli’s own protein synthesis pathways would then result in the expression of the RIPK2 protein. And the next step was protein purification. The purity of this recombinant protein is 90%+ determined by SDS-PAGE.

Receptor-interacting serine/threonine kinase 2 (RIPK2), also known as receptor-interacting protein 2 (RIP2), is a signaling molecule downstream of NOD2 and ATG16L1. Recent studies have provided evidence that excessive activation of RIPK2 is involved in the development of experimental and human bowel diseases. RIPK2 is expressed in antigen-presenting cells, such as dendritic cells and macrophages. Recognition of microbe-associated molecular patterns by NOD1, NOD2, and TLRs leads to the interaction between RIPK2 and these innate immune receptors, followed by the release of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12/23p40 through the activation of nuclear factor kappa B and mitogen-activated protein kinases. Thus, activation of RIPK2 plays a critical role in host defense against microbial infections. Recent experimental and clinical studies have provided evidence that activation of RIPK2 is involved in the development of autoimmune diseases, especially bowel diseases. In addition, the colonic mucosa of patients with bowel diseases exhibits enhanced expression of RIPK2 and associated signaling molecules. Furthermore, the blockage of RIPK2 activation ameliorates the development of experimental murine colitis. Thus, activation of RIPK2 underlies bowel diseases immunopathogenesis.

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Target Background

Function
Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation. Plays a role in the inactivation of RHOA in response to NGFR signaling.
Gene References into Functions
  1. Two Single-Nucleotide Polymorphisms associated with susceptibility to develop dengue in NOD1 or RIPK2 genes were observed Children from Colombia. PMID: 30332343
  2. Nine compounds from the ZINC database show satisfactory results, yielding among those selected, the compound ZINC01540228, as the most promising RIPK2 inhibitor. After binding free energy calculations, the following molecular dynamics simulations showed that the receptor protein's backbone remained stable after the introduction of ligands. PMID: 30088101
  3. Results showed that the expressions of RIP2 and BclxL were positively correlated with the malignant grade of astrocytoma. RIP2 promoted human glioblastoma cell proliferation by inducing expression of BclxL. PMID: 29693188
  4. Together, these data show that RIP2 promotes survival of breast cancer cells through NF-kappaB activation and that targeting RIP2 may be therapeutically beneficial for treatment of TNBC. PMID: 29421659
  5. RIP2 kinase auto-phosphorylation is intimately coupled to dimerization. PMID: 28545134
  6. study provides structural and dynamic insights into the NOD1-RIP2 oligomer formation, which will be crucial in understanding the molecular basis of NOD1-mediated CARD-CARD interaction in higher and lower eukaryotes PMID: 28114344
  7. a new function of PAX5 in regulating RIP1 and RIP2 activation, which is at least involved in chemotherapeutic drug resistance in B-lymphoproliferative disorders, is reported. PMID: 27122187
  8. this study reveals that LRRK2 is a new positive regulator of Rip2 and promotes inflammatory cytokine induction through the Nod1/2-Rip2 pathway. PMID: 27830463
  9. Data indicate that receptor-interacting protein 2 (Rip2) polymorphisms are associated with increased risk of subclinical atherosclerosis (SA) and with some clinical and metabolic parameters. PMID: 27939575
  10. Together, the data demonstrate that the NOD2-RIP2 pathway is activated in murine and human visceral leishmaniasis and plays a role in shaping adaptive immunity toward a Th1 profile. PMID: 27651416
  11. RIP2 and RhoGDI bind to p75(NTR) death domain at partially overlapping epitopes with over 100-fold difference in affinity, revealing the mechanism by which RIP2 recruitment displaces RhoGDI upon ligand binding. PMID: 26646181
  12. that Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia PMID: 26130752
  13. up-regulated in failing hearts PMID: 26463597
  14. NOD2 downregulates colonic inflammation by IRF4-mediated inhibition of K63-linked polyubiquitination of RICK and TRAF6. PMID: 24670424
  15. RIP2 protein, human is involved in human colon tumorigenesis and could be a predictive marker for colon carcinoma progression PMID: 25374171
  16. Data indicate that receptor-interacting protein kinase 2 (RIP2) is an activator of the NF-kappa B and c-Jun N-terminal kinase pathways. PMID: 24642040
  17. NOD1 and RIP2 interact with bacterial peptidoglycan on endosomes to promote autophagy and inflammatory signaling. PMID: 24746552
  18. the NOD1-RIP2 signaling axis is more complex than previously assumed, that simple engagement of RIP2 is insufficient to mediate signaling PMID: 24958724
  19. Receptor interacting protein-2 plays a critical role in human lung epithelial cells survival in response to Fas-induced cell-death. PMID: 24658576
  20. The Nod1/2-Rip2 axis was critical to induce optimal cytokine and chemokine responses to A. baumannii infection. PMID: 24366254
  21. LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations. PMID: 24015287
  22. Our findings identify RIP2 as a substrate for Pellino3 and Pellino3 as an important mediator in the Nod2 pathway and regulator of intestinal inflammation. PMID: 23892723
  23. In an attempt to explore TRAF3 binding partners that may be involved in TRAF3-regulated signaling, a yeast two-hybrid screen of a human spleen cDNA library was undertaken. RIP2 was identified as a TRAF3 binding partner. PMID: 23333941
  24. inositol phosphatase SHIP-1 inhibits NOD2-induced NF-kappaB activation by disturbing the interaction of XIAP with RIP2 PMID: 22815893
  25. RIPK2 might play an important role in hepatic cell migration. These findings could shed new light on carcinogenesis and on liver regeneration. PMID: 22993319
  26. Association has been found between RIPK2 (rs42490) and cancer risk. PMID: 22504414
  27. regulates reduced prostaglandin E2 production in chronic periodontitis PMID: 22828789
  28. RIP2 tyrosine kinase activity is not only required for NOD2-dependent autophagy but plays a dual role in this process. PMID: 22665475
  29. These findings mechanisms whereby HBeAg modulates intracellular signaling pathways by targeting RIPK2, supporting the concept that HBeAg could impair both innate and adaptive immune responses to promote chronic HBV infection. PMID: 22615316
  30. IL-4 failed to up-regulate expression of RP105 at the cell surface. In conclusion, the anti-inflammatory actions of IL-4 occur independently of IL-10, RP105, and the kinase activity of RIPK2 PMID: 22484241
  31. RIP2 gene polymorphisms may be associated with susceptibility to systemic lupus erythematosus in the Chinese population. PMID: 22075569
  32. GEF-H1 mediated the activation of Rip2 during signaling by NOD2, but not in the presence of the 3020insC variant of NOD2 associated with Crohn's disease. GEF-H1 functioned downstream of NOD2 as part of Rip2-containing signaling complexes. PMID: 21887730
  33. the CARD of procaspase-1 is differently involved in the formation of procaspase-1 activating platforms and procaspase-1-mediated, RIP2-dependent NF-kappaB activation. PMID: 21862576
  34. Tri-DAP interacts directly with the LRR domain of NOD1 and consequently increases RICK/NOD1 association and RICK phosphorylation activity PMID: 21757725
  35. RIP2 polymorphisms are not associated with inflammatory bowel diseases. PMID: 20645315
  36. RIP2 undergoes autophosphorylation on Tyr 474 and this event is necessary for effective NOD2 signaling PMID: 21123652
  37. MS80 inhibits CD40-NF-kappaB pathway via targeting RIP2. PMID: 19911254
  38. detected on all female reproductive tract tissues PMID: 19406482
  39. Data suggest that inhibition of rip2 upregulation after wounding might contribute to the reduced and delayed wound re-epithelialization phenotype seen in glucocorticoid-treated patients. PMID: 20025869
  40. Elevated RIP-2 protein levels promote NF-kappaB function via interaction with IKK gamma PMID: 19693652
  41. the NOD2/RIP2 pathway has a role in recognition of Yersinia, but caspase-12 does not modulate innate host defense against Y. pestis PMID: 19721713
  42. Involvement of receptor-interacting protein 2 in innate and adaptive immune responses PMID: 11894097
  43. These results implicate RIP2 in a previously unrecognized role: a checkpoint for myogenic proliferation and differentiation. PMID: 12138198
  44. equilibrium and kinetic folding of a unique protein domain, caspase recruitment domain (CARD), of the RIP-like interacting CLARP kinase (RICK) (RICK-CARD), which adopts a alpha-helical Greek key fold PMID: 12755636
  45. role in CARD6 modulation of NF-kappa B activation PMID: 12775719
  46. Rip2 has an important role in TCR-induced NF-kappaB activation and T-cell function PMID: 14638696
  47. NOD2-dependent ubiquitinylation of NEMO (a key component of the NF-kB signaling complex) is dependent on the scaffolding protein kinase RIP2. PMID: 15620648
  48. Caspase-1-mediated cell death is regulated, at least in part, by the balance of Rip2 and Cop; alterations of this balance may contribute to aberrant caspase-1-mediated pathogenesis in Huntington's disease. PMID: 16354923
  49. CARD6 is a regulator of NF-kappaB activation that modulates the functions of RICK protein PMID: 16418290
  50. NOD2-S interacts with both, NOD2 and receptor-interacting protein kinase 2 and inhibits the "nodosome" assembly by interfering with the oligomerization of NOD2 PMID: 16492792

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Subcellular Location
Cytoplasm.
Protein Families
Protein kinase superfamily, TKL Ser/Thr protein kinase family
Tissue Specificity
Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas and lymph node.
Database Links

HGNC: 10020

OMIM: 603455

KEGG: hsa:8767

STRING: 9606.ENSP00000220751

UniGene: Hs.103755

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