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RIPK2

  • Official Full Name

    receptor-interacting serine-threonine kinase 2

  • Overview

    This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein contains a C-terminal caspase activation and recruitment domain (CARD), and is a component of signaling complexes in both the innate and adaptive immune pathways. It is a potent activator of NF-kappaB and inducer of apoptosis in response to various stimuli. [provided by RefSeq, Jul 2008]
  • Synonyms

    RIPK2; receptor-interacting serine-threonine kinase 2; CCK; RICK; RIP2; CARD3; GIG30; CARDIAK; receptor-interacting serine/threonine-protein kinase 2; RIP-2; CARD-carrying kinase; growth-inhibiting gene 30; tyrosine-protein kinase RIPK2; receptor-interacting protein 2; CARD-containing IL-1 beta ICE-kinase; CARD-containing interleukin-1 beta-converting enzyme (ICE)-associated kinase; receptor-interacting protein (RIP)-like interacting caspase-like apoptosis regulatory protein (CLARP) kinase;

  • Recombinant Proteins
  • Cell & Tissue Lysates
  • Protein Pre-coupled Magnetic Beads
  • Chicken
  • Human
  • Mouse
  • Rat
  • Zebrafish
  • E.coli
  • HEK293
  • HEK293T
  • In Vitro Cell Free System
  • Insect Cell
  • Mamanlian cells
  • Mammalian Cell
  • Sf9 Insect Cell
  • Wheat Germ
  • Flag
  • GST
  • His
  • Fc
  • Avi
  • T7
  • Myc
  • DDK
  • Non
Species Cat.# Product name Source (Host) Tag Protein Length Price
Human RIPK2-419H Active Recombinant Human RIPK2, His-tagged Insect Cell His amino acids 1-299
Human RIPK2-1479H Active Recombinant Human RIPK2, GST-tagged Sf9 Insect Cell GST 1-299 aa
Human RIPK2-29983TH Recombinant Human RIPK2 Non 1-299
Human RIPK2-532H Recombinant Full Length Human RIPK2, MYC/DDK-tagged HEK293 Myc&DDK
Human RIPK2-711H Recombinant Human RIPK2, GST-His Sf9 Insect Cell GST M1-E299
Human RIPK2-418H Recombinant Human RIPK2, GST-tagged, Active Sf9 Insect Cell GST 1-299
Human RIPK2-932H Recombinant Human RIPK2 protein, His-tagged E.coli His Gln432~Met540
Human RIPK2-2333HCL Recombinant Human RIPK2 293 Cell Lysate HEK293 Non
Human RIPK2-5269HFL Recombinant Full Length Human RIPK2, Flag-tagged Mamanlian cells Flag
Human RIPK2-5565H Recombinant Human RIPK2, GST-tagged Wheat Germ GST 1-540 a.a.
Human RIPK2-6505H Recombinant Human RIPK2 Protein, Myc/DDK-tagged, C13 and N15-labeled HEK293T Myc&DDK
Human RIPK2-5564H Recombinant Full Length Human RIPK2 Protein, His-tagged E.coli His 1-540 aa
Human RIPK2-6795HF Recombinant Full Length Human RIPK2 Protein, GST-tagged In Vitro Cell Free System GST 540 amino acids
Human RIPK2-3761H Recombinant Human RIPK2 protein, His-tagged E.coli His 221-524 aa
Human RIPK2-6660H Recombinant Human RIPK2 Protein (Gln432-Met540), N-GST tagged E.coli GST Gln432-Met540
Human RIPK2-645H Recombinant Human RIPK2 protein, His-tagged E.coli His 1-540aa
Human RIPK2-755H Recombinant Human RIPK2 protein, GST-tagged E.coli GST 1-540aa
Mouse Ripk2-1795M Recombinant Mouse Ripk2 protein, His & T7-tagged E.coli His&T7 Met1~Leu294
Mouse RIPK2-14244M Recombinant Mouse RIPK2 Protein Mammalian Cell His
Mouse Ripk2-5522M Recombinant Mouse Ripk2 Protein, Myc/DDK-tagged HEK293T Myc&DDK
Mouse RIPK2-7616M Recombinant Mouse RIPK2 Protein, His (Fc)-Avi-tagged HEK293 His&Fc&Avi
Mouse RIPK2-7616M-B Recombinant Mouse RIPK2 Protein Pre-coupled Magnetic Beads HEK293
Rat Ripk2-1796R Recombinant Rat Ripk2 protein, His & T7-tagged E.coli His&T7 Met1~Leu294
Zebrafish RIPK2-9761Z Recombinant Zebrafish RIPK2 Mammalian Cell His
Chicken RIPK2-2632C Recombinant Chicken RIPK2 Mammalian Cell His
  • Background
  • Quality Guarantee
  • Case Study
  • Involved Pathway
  • Protein Function
  • Interacting Protein
  • RIPK2 Related Signal Pathway

What is RIPK2 protein?

RIPK2 (receptor interacting serine/threonine kinase 2) gene is a protein coding gene which situated on the long arm of chromosome 8 at locus 8q21. This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein contains a C-terminal caspase activation and recruitment domain (CARD), and is a component of signaling complexes in both the innate and adaptive immune pathways. It is a potent activator of NF-kappaB and inducer of apoptosis in response to various stimuli. The RIPK2 protein is consisted of 540 amino acids and its molecular mass is approximately 61.2 kDa.

What is the function of RIPK2 protein?

RIPK2 plays a role in a variety of cellular processes, including immune response, cell proliferation, and cell death. It consists of several key domains, including a kinase domain (KD), an intermediate domain (INTD), and a hemipascaspase activation and recruitment domain (CARD). The activation of RIPK2 can occur in a variety of ways, including autophosphorylation and ubiquitination, which leads to the activation of downstream signaling pathways, such as the NF-κB and MAPK pathways, which trigger the production and release of inflammatory cytokines.

RIPK2 Related Signaling Pathway

RIPK2 has a role in both classical and non-classical NF-κB activation pathways and is involved in the regulation of inflammatory responses and anti-apoptotic processes. As a member of the NOD-like receptor family, RIPK2 is able to bind to NLRP1 and activate downstream inflammatory responses, thereby promoting caspase-1 activation and the maturation and release of pro-inflammatory cytokines such as IL-1β. Studies have shown that RIPK2 plays a role in regulating TNF-induced apoptosis and programmed necrosis, and may interact with other proteins such as RIPK1 and MLKL. As part of innate immunity, RIPK2 is also involved in recognizing pathogen-associated molecular patterns (PAMPs) and DAMPs (damage associated molecular patterns), which in turn activate downstream signaling cascades.

Mechanism of NOD2 Signaling Blockade by RIP2 Kinase Inhibitors and XIAP BIR2 Antagonists.jpg

Fig1. Mechanism of NOD2 Signaling Blockade by RIP2 Kinase Inhibitors and XIAP BIR2 Antagonists. (Shiyu Xia, 2018)

RIPK2 Related Diseases

Abnormal RIPK2 function has been linked to a variety of diseases, including: autoimmune diseases such as rheumatoid arthritis (RA), in which RIPK2 may play a key role in regulating inflammation and joint damage. Inflammatory bowel diseases include Crohn's disease and ulcerative colitis. Due to its role in the immune system, RIPK2 is also important in responding to bacterial, viral, and other pathogen infections. Certain types of tumors are associated with alterations in the expression or function of RIPK2, which may affect cell survival and proliferation. There are also cardiovascular diseases, metabolic diseases and so on.

Bioapplications of RIPK2

Small molecule inhibitors targeting RIPK2 and PROTACs (protein degradation targeting chimeras) have shown potential in the treatment of inflammatory diseases. These molecules are able to inhibit the activity of RIPK2 or promote its degradation, thereby reducing the inflammatory response and improving disease symptoms.

High Purity

SDS-PAGE (RIPK2-214H).jpg

Fig1. SDS-PAGE (RIPK2-214H)

High Bioactivity

Activity Data (RIPK2-214H).jpg

Fig2. Activity Data (RIPK2-214H)

Case Study 1: Xiao-Liang Wang, 2022

This study aimed to investigate the role of receptor-interacting protein 2 (RIP2) in regulation of stemness of glioma cells and chemotherapy resistance. Plasmid transfection was used to overexpress RIP2. Chemical inhibitors were used to inhibit RIP2 or NF-κB activity. Cancer stemness of glioma cells was investigated by sphere formation assays, clone formation assays, and xenograft tumor formation assays. The expression of RIP2, p-NF-κB, IκBα, CD133, or SOX-2 was detected by Western blotting and immunofluorescence. Apoptosis was detected by flow cytometry. Immunohistochemical staining was used to detect the expression of RIP2, CD133, and SOX-2 in xenograft tumor tissue. Transfection with RIP2 plasmid enhanced the sphere formation capability of U251 cells, clone formation capability, and xenograft tumor formation capability. RIP2 could mediate TMZ resistance by upregulating the expression of CD133 and SOX-2 by activating the NF-κB pathway. Both RIP2 inhibitor GSK583 and the NF-κB inhibitor SC75741 could reverse the resistance of U251 cells to TMZ.

Different glioma cells were treated with gradient concentrations of rRIP2.jpg

Fig1. Different glioma cells were treated with gradient concentrations of rRIP2 for 24 h and then TMZ was added for 72 h, and cell viability was detected by CCK-8 assay.

U251 cells were treated with rRIP2.jpg

Fig2. U251 cells were treated with 100, 200, and 400 ng/mL rRIP2 for 24 h, and the expressions of CD133 and SOX-2 were detected by Western blotting.

Case Study 2: Yiwu Yan, 2022

Despite progress in prostate cancer (PC) therapeutics, distant metastasis remains a major cause of morbidity and mortality from PC. Thus, there is growing recognition that preventing or delaying PC metastasis holds great potential for substantially improving patient outcomes. This study shows receptor-interacting protein kinase 2 (RIPK2) is a clinically actionable target for inhibiting PC metastasis. RIPK2 is amplified/gained in ~65% of lethal metastatic castration-resistant PC. Its overexpression is associated with disease progression and poor prognosis, and its genetic knockout substantially reduces PC metastasis. Multi-level proteomics analyses reveal that RIPK2 strongly regulates the stability and activity of c-Myc (a driver of metastasis), largely via binding to and activating mitogen-activated protein kinase kinase 7 (MKK7), which we identify as a direct c-Myc-S62 kinase. RIPK2 inhibition by preclinical and clinical drugs inactivates the noncanonical RIPK2/MKK7/c-Myc pathway and effectively impairs PC metastatic outgrowth.

Comparison of RIPK2 protein levels in six commonly used prostate cell line models.jpg

Fig3. Comparison of RIPK2 protein levels in six commonly used prostate cell line models.

Representative images of Co-IP analysis detecting the association of RIPK2 and MKK7.jpg

Fig4. Representative images of Co-IP analysis detecting the association of RIPK2 and MKK7 ectopically expressed in RIPK2/MKK7-DKO HEK293T cells.

RIPK2 involved in several pathways and played different roles in them. We selected most pathways RIPK2 participated on our site, such as NOD-like receptor signaling pathway, Neurotrophin signaling pathway, Shigellosis, which may be useful for your reference. Also, other proteins which involved in the same pathway with RIPK2 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

Pathway Name Pathway Related Protein
NOD-like receptor signaling pathwayNAIP7;NLRC4;PYDC1;NAIP1;IL-8;Ccl12;IL18;NFKBIAA;CASP1
Neurotrophin signaling pathwayMAPK13;MAP3K1;BAD;RAF1;CALML5;PIK3CD;RHOA;NGFR;IRAK2
ShigellosisRHOG;U2AF1;ELMO3;VCL;RELA;CDC42;PFN3;MAPK13;MAPK10
TuberculosisRFXANK;ATP6V1H;FCGR2C;CAMK2D;PMAP-36;BID;ITGB2L;ATP6V0A1;IL18

RIPK2 has several biochemical functions, for example, ATP binding, CARD domain binding, LIM domain binding. Some of the functions are cooperated with other proteins, some of the functions could acted by RIPK2 itself. We selected most functions RIPK2 had, and list some proteins which have the same functions with RIPK2. You can find most of the proteins on our site.

Function Related Protein
ATP bindingKIF17;MKNK2A;MLKL;FARSA;TTLL10;TSSK4;ROR2;CKBB;STK10
CARD domain bindingRIPK2;MAVS;CARD9;CARD11;NOD1;C9orf89;CARD14
LIM domain bindingACTN2;LDB2B;LDB2A;LDB1B;TLN1;LDB1A;CSRP2BP;LDB2;LDB1
non-membrane spanning protein tyrosine kinase activityFES;PTK6;FRK;STYK1;LCK;FYNA;PTK2;SRC;MATK
protein bindingCSF2RB;SQSTM1;XCL2;FAM158A;FAM98A;HIST1H4L;PFDN2;WDR24;ERBB4
protein homodimerization activityGLA;SIAH1A;MECOM;SLC9A7;HPGD;ADD2;APOA4;CEBPE;TGFB1
protein serine/threonine kinase activitySRPK2;SBK1;ADCK4;BMPR1AA;TTK;TSSK5;STK3;MYLK4;PLK4
receptor bindingGUSB;ACOT2;SMARCD3;CRAT;GSTK1;ANXA1;SSFA2;PECI;ANGPTL1
signal transducer activityGPR34A;V2RX1;MRGPRB5;TAAR10B;OLFR488;GPR158;GNA12;PLCG2;PTK2BB

RIPK2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with RIPK2 here. Most of them are supplied by our site. Hope this information will be useful for your research of RIPK2.

XIAP; NOD2; TRAF3; BIRC3; BIRC2; TRAF2

  • Reviews
  • Q&As

Customer Reviews (3)

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Reviews
12/13/2019

    Precise mass spectrometry analysis, key for our proteomics investigations.

    04/07/2019

      Dependable protein purification, consistently delivers high yield and purity.

      11/23/2018

        Great antibody validation, enhances our immunoprecipitation success.

        Q&As (7)

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        What role does RIPK2 play in the inflammatory response, particularly in the context of autoimmune diseases? 06/11/2020

        RIPK2 plays a significant role in driving inflammatory responses, implicated in autoimmune disease mechanisms.

        How does RIPK2 mediate signal transduction in the NOD1 and NOD2 pathways involved in innate immunity? 04/30/2020

        RIPK2 is crucial in NOD1/NOD2 signaling, activating innate immune responses against microbial intrusions.

        How do alterations in RIPK2 expression or signaling affect cancer development and progression? 12/29/2019

        Changes in RIPK2 signaling can impact cancer development, influencing tumor cell survival and immune interactions.

        How does RIPK2 contribute to the regulation of NF-κB activation and cytokine production? 02/04/2019

        RIPK2 regulates NF-κB activation and cytokine production, crucial for immune response and inflammation.

        What are the mechanisms by which RIPK2 modulates the host defense against bacterial pathogens? 03/30/2018

        RIPK2 modulates defense mechanisms against bacterial pathogens, coordinating immune signaling and responses.

        How does RIPK2 influence cell survival and apoptosis, especially under conditions of stress or infection? 03/24/2018

        RIPK2 influences cell survival and apoptosis decisions, particularly in response to stress or microbial infection.

        What is the impact of RIPK2 dysregulation on the development and progression of inflammatory bowel disease (IBD)? 02/21/2018

        Dysregulation of RIPK2 is linked to IBD, affecting intestinal inflammation and immune responses.

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