Product Details

Purity

Greater than 90% as determined by SDS-PAGE.

Target Names

RIPK3

Uniprot No.

Q9Y572

Research Area

Cell Biology

Alternative Names

Receptor interacting protein 3; Receptor interacting serine threonine kinase 3; Receptor interacting serine/threonine protein kinase 3; Receptor-interacting protein 3; Receptor-interacting serine/threonine-protein kinase 3; RIP 3; RIP like protein kinase 3; RIP-3; RIP-like protein kinase 3; RIPK 3; RIPK3; RIPK3_HUMAN

Species

Homo sapiens (Human)

Source

E.coli

Expression Region

1-518aa

Target Protein Sequence

MSCVKLWPSGAPAPLVSIEELENQELVGKGGFGTVFRAQHRKWGYDVAVKIVNSKAISREVKAMASLDNEFVLRLEGVIEKVNWDQDPKPALVTKFMENGSLSGLLQSQCPRPWPLLCRLLKEVVLGMFYLHDQNPVLLHRDLKPSNVLLDPELHVKLADFGLSTFQGGSQSGTGSGEPGGTLGYLAPELFVNVNRKASTASDVYSFGILMWAVLAGREVELPTEPSLVYEAVCNRQNRPSLAELPQAGPETPGLEGLKELMQLCWSSEPKDRPSFQECLPKTDEVFQMVENNMNAAVSTVKDFLSQLRSSNRRFSIPESGQGGTEMDGFRRTIENQHSRNDVMVSEWLNKLNLEEPPSSVPKKCPSLTKRSRAQEEQVPQAWTAGTSSDSMAQPPQTPETSTFRNQMPSPTSTGTPSPGPRGNQGAERQGMNWSCRTPEPNPVTGRPLVNIYNCSGVQVGDNNYLTMQQTTALPTWGLAPSGKGRGLQHPPPVGSQEGPKDPEAWSRPQGWYNHSGK
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

72.9kDa

Protein Length

Full Length

Tag Info

N-terminal 6xHis-SUMO-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

The region for expressing recombinant Human RIPK3 contains amino acids 1-518. The theoretical molecular weight of the RIPK3 protein is 72.9 kDa. This RIPK3 protein is produced using e.coli expression system. The N-terminal 6xHis-SUMO tag was fused into the coding gene segment of RIPK3, making it easier to detect and purify the RIPK3 recombinant protein in the later stages of expression and purification.

The human receptor-interacting serine/threonine-protein kinase 3 (RIPK3) is a member of the RIP kinase family and is involved in regulating programmed cell death, particularly necroptosis, a form of regulated necrosis. RIPK3 plays a crucial role in immune responses, inflammation, and tissue homeostasis. Upon activation, RIPK3 forms a complex with other proteins, leading to the phosphorylation of downstream effectors and ultimately triggering necroptosis. Additionally, RIPK3 has been implicated in other cellular processes, including the regulation of inflammatory signaling pathways. Research on RIPK3 aims to understand its intricate functions in cell death and inflammation, offering insights into potential therapeutic strategies for various diseases, including inflammatory disorders and certain cancers.

Target Background

Function

Serine/threonine-protein kinase that activates necroptosis and apoptosis, two parallel forms of cell death. Necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members, is triggered by RIPK3 following activation by ZBP1. Activated RIPK3 forms a necrosis-inducing complex and mediates phosphorylation of MLKL, promoting MLKL localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage. In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol. Also regulates apoptosis: apoptosis depends on RIPK1, FADD and CASP8, and is independent of MLKL and RIPK3 kinase activity. Phosphorylates RIPK1: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. In some cell types, also able to restrict viral replication by promoting cell death-independent responses. In response to Zika virus infection in neurons, promotes a cell death-independent pathway that restricts viral replication: together with ZBP1, promotes a death-independent transcriptional program that modifies the cellular metabolism via up-regulation expression of the enzyme ACOD1/IRG1 and production of the metabolite itaconate. Itaconate inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production.; (Microbial infection) In case of herpes simplex virus 1/HHV-1 infection, forms heteromeric amyloid structures with HHV-1 protein RIR1/ICP6 which may inhibit RIPK3-mediated necroptosis, thereby preventing host cell death pathway and allowing viral evasion.

Gene References into Functions

The major function of RIP1 kinase activity in TNF-induced necroptosis is to autophosphorylate serine 161. This specific phosphorylation then enables RIP1 to recruit RIP3 and form a functional necrosome, a central controller of necroptosis. PMID: 28176780
RIPK3-dependent cell death and inflammasome activation in FLT3-internal-tandem-duplication-expressing leukemia-initiating cells PMID: 27517160
The necroptosis-inducing kinase RIPK3 reduces adipose tissue inflammation and glucose intolerance. PMID: 27323669
We showed that RIP3 spontaneously drives a necroptosis-induced inflammation in established intestinal cell lines and in ileal/colonic samples from IBD patients. PMID: 28844856
These data demonstrate that caspase-8 functions in synovial antigen-presenting cells to regulate the response to inflammatory stimuli by controlling RIPK3 action, and this delicate balance maintains homeostasis within the joint. PMID: 28978351
The induced expression of RIP3 by UHRF1 RNAi depends on the presence of Sp1. Remarkably, the ectopic expression of RIP3 in RIP3-null cancer cells results in a decrease in tumor growth in mice. Therefore, our findings offer insights into RIP3 expression control in cancer cells and suggest an inhibitory effect of RIP3 on tumorigenesis. PMID: 28981102
2-hydroxyglutarate bound to DNMT1 and stimulated its association with the RIP3 promoter, inducing hypermethylation that reduces RIP3 protein and consequently impaired RIP3-dependent necroptosis. PMID: 28564603
the in vivo effects were diametrically reversed with RIP3 deletion or RIP1 blockade, resulting in marked tumor protection. The dichotomy between the in vivo and in vitro results suggests that the microenvironmental milieu resulting from RIP1/RIP3 signaling is likely responsible for its protumorigenic effects PMID: 27932417
Shikonin induces glioma cell necroptosis in vitro by reactive oxygen species overproduction and promoting RIP1/RIP3 necrosome formation. PMID: 28816233
In critically ill trauma patients, plasma levels of the necroptosis mediator RIP3 at 48 h were associated with AKI stage and RBC transfusions. PMID: 26925809
our results reveal that the necroptosis adaptor RIPK3 has key anti-inflammatory and anti-tumoral functions in the intestine, and define RIPK3 as a novel colon tumor suppressor PMID: 27344176
adhesion-induced eosinophil cytolysis takes place through RIPK3-MLKL-dependent necroptosis, which can be counterregulated by autophagy PMID: 28412393
Renal clear cell carcinoma cells cells express increased amounts of RIPK1 and RIPK3 and are poised to undergo necroptosis in response to TNFR1 signaling. PMID: 27362805
The results highlight a new role of TSC2 in protecting glioblastoma against photodynamic therapy-induced cell death, and TSC2 and YWHAZ as new RIP3 partners. PMID: 27984090
inactivation of RIP1/RIP3 resulted in reduction of SOCS1 protein levels and partial differentiation of AML cells. AML cells with inactivated RIP1/RIP3 signaling show increased sensitivity to IFN-gamma-induced differentiation. PMID: 27748372
results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases. PMID: 27756058
Necroptosis signaling is modulated by the kinase RIPK1 and requires the kinase RIPK3 and the pseudokinase MLKL. (Review) PMID: 26865533
Results demonstrate that RIPK3 restricts malignant myeloproliferation by activating the inflammasome, which promotes differentiation and cell death, and that loss of RIPK3 increases leukemic burden in mice. Reduced RIPK3 expression is observed across several human acute myeloid leukemia subtypes. PMID: 27411587
Data identify RIPK3 and the inflammasome as key tumor suppressors in acute myeloid leukemia (AML). PMID: 27411587
The main route of cell death induced by shikonin is RIP1K-RIP3K-mediated necroptosis. PMID: 26496737
Results suggest that impaired hepatic proteasome function by alcohol exposure may contribute to hepatic accumulation of RIP3 resulting in necroptosis and steatosis while RIP1 kinase activity is important for alcohol-induced inflammation. PMID: 26769846
The expression level of RIP3K was significantly lower in the malignant tumors. PMID: 26749282
CNOT3 suppression promotes necroptosis by stabilizing mRNAs for cell death-inducing proteins, Ripk1 and Ripk3. PMID: 26437789
RIPK3 expression may allow unmasking the necroptotic signalling machinery in melanoma and points to reactivation of this pathway as a treatment option for metastatic melanoma. PMID: 26355347
Additionally, later in infection, RIP3 is cleaved by the coxsackievirus B3-encoded cysteine protease 3C(pro), which serves to abrogate RIP3-mediated necrotic signaling and induce a nonnecrotic form of cell death. PMID: 26269957
although JNK activation and RIP3 expression are induced by FS, neither contributes to the liver injury. PMID: 25423287
The RIP3 expression is reduced in tumors compared to normal tissue in 85% of breast cancer patients, suggesting that RIP3 deficiency is positively selected during tumor growth/development. PMID: 25952668
Data implicate the infiltrating macrophages as a source of damaging inflammasomes after photoreceptor detachment in a RIP3-dependent manner and suggest a novel therapeutic target for treatment of retinal diseases. PMID: 25906154
PolyIC stimulation of cervical cancer cells induced necroptotic cell death, which was strictly dependent on the expression of the receptor-interacting protein kinase RIPK3. PMID: 25888634
Data suggest that neoalbaconol-induced necroptosis include receptor interacting serine/threonine kinase 1-dependent expression of tumor necrosis factor alpha and receptor interacting serine/threonine kinase 3-dependent generation of reactive oxygen species. PMID: 25575821
Herpes simplex virus 1- and 2 ICP6 and ICP10 proteins prevent necroptosis in human cells by inhibiting the interaction between receptor-interacting protein kinase 1 (RIP1) and RIP3, a key step in tumor necrosis factor (TNF)-induced necroptosis. PMID: 25674983
High expression of RIP3 in keratinocytes from toxic epidermal necrolysis patients potentiates MLKL phosphorylation/activation and necrotic cell death. PMID: 25748555
RIP3 silencing in leukemia cells results in suppression of the complex regulation of the apoptosis/necroptosis switch and NF-kappaB activity. PMID: 25144719
Suppression of RIP3-dependent necroptosis by human cytomegalovirus PMID: 25778401
RIP3 activation following the induction of necroptosis requires the activity of an HSP90 and CDC37 cochaperone complex. PMID: 25852146
The results of this study showed that cerebral ischemia activates transcriptional changes that lead to an increase in the endogenous RIP3 protein level. PMID: 24746856
Enhanced RIP3 signaling in aneurysmal tissues contributes to abdominal aortic aneursym progression by causing smooth muscle cell necroptosis, as well as stimulating vascular inflammation. PMID: 25563840
RIP3-dependent necroptosis mediates non-alcoholic steatohepatitis-induced liver fibrosis via activation of JNK, MCP-1-mediated recruitment of monocytes, and an expansion of intrahepatic biliary/progenitor cells. PMID: 24963148
RIPK3 serves as a negative regulator of selective autophagy by regulating regulates p62-LC3 complex formation via the caspase-8-dependent cleavage of p62 PMID: 25450619
RIP3 holds both necroptosis and apoptosis in balance through a Ripoptosome-like platform. PMID: 25459880
an alanine residue substitution for Ser(89) enhanced RIP1 kinase activity and TNF-induced programmed necrosis without affecting RIP1-RIP3 necrosome formation. PMID: 24059293
targeting the RIP kinase signalling pathway could be an effective therapeutic intervention in retinal degeneration patients. PMID: 24413151
RIP3-mediated MLKL phosphorylation, though important for downstream signaling, is dispensable for stable complex formation between RIP3 and MLKL. PMID: 24095729
Report role of MLKL/RIP3 pathway in necrotic membrane disruption. PMID: 24703947
RIP3 protein expression is significantly increased in the inflamed tissue of inflammatory boowel disease pediatric patients. PMID: 24322838
The protein levels of crucial modulators of necroptosis, RIP1 and RIP3, are increased by shikonin treatment in primary tumor tissues. PMID: 24314238
the importance of the RIP3-MLKL interaction in the formation of functional necrosomes and suggest that translocation of necrosomes to mitochondria-associated membranes is essential for necroptosis signaling. PMID: 23612963
procaspase-8 activity is essential for cell survival by inhibiting both apoptotic and nonapoptotic cell death dependent on receptor-interacting protein kinase 1 (RIP1) and RIP3 PMID: 23071110
Study shows that RIP1 and RIP3 form an amyloid structure through their RIP homotypic interaction motifs and that this heterodimeric amyloid structure is a functional signaling complex that mediates programmed necrosis. PMID: 22817896
study suggests that MLKL is a key RIP3 downstream component of TNF-induced necrotic cell death PMID: 22421439

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Subcellular Location

Cytoplasm, cytosol. Nucleus.

Protein Families

Protein kinase superfamily, TKL Ser/Thr protein kinase family

Tissue Specificity

Highly expressed in the pancreas. Detected at lower levels in heart, placenta, lung and kidney.; [Isoform 3]: Expression is significantly increased in colon and lung cancers.

Database Links

HGNC: 10021

OMIM: 605817

KEGG: hsa:11035

STRING: 9606.ENSP00000216274

UniGene: Hs.268551

Code	CSB-EP897497HU
Abbreviation	Recombinant Human RIPK3 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 3 (RIPK3)

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