Product Details

Purity

Greater than 90% as determined by SDS-PAGE.

Target Names

RIPK2

Uniprot No.

O43353

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 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

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.

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

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.

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

Two Single-Nucleotide Polymorphisms associated with susceptibility to develop dengue in NOD1 or RIPK2 genes were observed Children from Colombia. PMID: 30332343
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
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
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
RIP2 kinase auto-phosphorylation is intimately coupled to dimerization. PMID: 28545134
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
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
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
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
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
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
that Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia PMID: 26130752
up-regulated in failing hearts PMID: 26463597
NOD2 downregulates colonic inflammation by IRF4-mediated inhibition of K63-linked polyubiquitination of RICK and TRAF6. PMID: 24670424
RIP2 protein, human is involved in human colon tumorigenesis and could be a predictive marker for colon carcinoma progression PMID: 25374171
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
NOD1 and RIP2 interact with bacterial peptidoglycan on endosomes to promote autophagy and inflammatory signaling. PMID: 24746552
the NOD1-RIP2 signaling axis is more complex than previously assumed, that simple engagement of RIP2 is insufficient to mediate signaling PMID: 24958724
Receptor interacting protein-2 plays a critical role in human lung epithelial cells survival in response to Fas-induced cell-death. PMID: 24658576
The Nod1/2-Rip2 axis was critical to induce optimal cytokine and chemokine responses to A. baumannii infection. PMID: 24366254
LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations. PMID: 24015287
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
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
inositol phosphatase SHIP-1 inhibits NOD2-induced NF-kappaB activation by disturbing the interaction of XIAP with RIP2 PMID: 22815893
RIPK2 might play an important role in hepatic cell migration. These findings could shed new light on carcinogenesis and on liver regeneration. PMID: 22993319
Association has been found between RIPK2 (rs42490) and cancer risk. PMID: 22504414
regulates reduced prostaglandin E2 production in chronic periodontitis PMID: 22828789
RIP2 tyrosine kinase activity is not only required for NOD2-dependent autophagy but plays a dual role in this process. PMID: 22665475
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
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
RIP2 gene polymorphisms may be associated with susceptibility to systemic lupus erythematosus in the Chinese population. PMID: 22075569
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
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
Tri-DAP interacts directly with the LRR domain of NOD1 and consequently increases RICK/NOD1 association and RICK phosphorylation activity PMID: 21757725
RIP2 polymorphisms are not associated with inflammatory bowel diseases. PMID: 20645315
RIP2 undergoes autophosphorylation on Tyr 474 and this event is necessary for effective NOD2 signaling PMID: 21123652
MS80 inhibits CD40-NF-kappaB pathway via targeting RIP2. PMID: 19911254
detected on all female reproductive tract tissues PMID: 19406482
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
Elevated RIP-2 protein levels promote NF-kappaB function via interaction with IKK gamma PMID: 19693652
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
Involvement of receptor-interacting protein 2 in innate and adaptive immune responses PMID: 11894097
These results implicate RIP2 in a previously unrecognized role: a checkpoint for myogenic proliferation and differentiation. PMID: 12138198
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
role in CARD6 modulation of NF-kappa B activation PMID: 12775719
Rip2 has an important role in TCR-induced NF-kappaB activation and T-cell function PMID: 14638696
NOD2-dependent ubiquitinylation of NEMO (a key component of the NF-kB signaling complex) is dependent on the scaffolding protein kinase RIP2. PMID: 15620648
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
CARD6 is a regulator of NF-kappaB activation that modulates the functions of RICK protein PMID: 16418290
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

Code	CSB-EP019736HU
Abbreviation	Recombinant Human RIPK2 protein
MSDS	MSDS Datasheet
Size	$224
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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 Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)

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