Product Details

Purity

Greater than 85% as determined by SDS-PAGE.

Target Names

RIPK1

Uniprot No.

Q13546

Research Area

Cell Biology

Alternative Names

Cell death protein RIP; FLJ39204; OTTHUMP00000039163; Receptor (TNFRSF) interacting serine threonine kinase 1; receptor interacting protein 1; Receptor interacting protein; Receptor interacting protein kinase 1; Receptor interacting serine threonine protein kinase 1; Receptor TNFRSF interacting serine threonine kinase 1; Receptor-interacting protein 1; Receptor-interacting serine/threonine-protein kinase 1; Rinp; RIP 1; RIP; Rip-1; RIP1; RIPK 1; Ripk1; RIPK1_HUMAN; Serine threonine protein kinase RIP; Serine/threonine-protein kinase RIP

Species

Homo sapiens (Human)

Source

E.coli

Expression Region

1-375aa

Target Protein Sequence

MQPDMSLNVIKMKSSDFLESAELDSGGFGKVSLCFHRTQGLMIMKTVYKGPNCIEHNEALLEEAKMMNRLRHSRVVKLLGVIIEEGKYSLVMEYMEKGNLMHVLKAEMSTPLSVKGRIILEIIEGMCYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFKMWSKLNNEEHNELREVDGTAKKNGGTLYYMAPEHLNDVNAKPTEKSDVYSFAVVLWAIFANKEPYENAICEQQLIMCIKSGNRPDVDDITEYCPREIISLMKLCWEANPEARPTFPGIEEKFRPFYLSQLEESVEEDVKSLKKEYSNENAVVKRMQSLQLDCVAVPSSRSNSATEQPGSLHSSQGLGMGPVEESWFAPSLEHPQEENEPSLQ
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

49.4 kDa

Protein Length

Partial

Tag Info

N-terminal 10xHis-tagged and C-terminal Myc-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 expression region of this recombinant Human RIPK1 covers amino acids 1-375. The expected molecular weight for the RIPK1 protein is calculated to be 49.4 kDa. The RIPK1 protein was expressed in e.coli. Fusion of the N-terminal 10xHis tag and C-terminal Myc tag into the RIPK1 encoding gene fragment was conducted, allowing for easier detection and purification of the RIPK1 protein in subsequent stages.

Human receptor-interacting Serine/Threonine-Protein kinase 1 (RIPK1) is a pivotal regulator of cell survival and inflammation. Acting as a signaling node in death receptor pathways, RIPK1 controls cell fate decisions by modulating apoptosis, necroptosis, and inflammation. In immunology research, RIPK1 is essential for immune response modulation. Dysregulation of RIPK1 is implicated in inflammatory and autoimmune diseases. In cancer research, its role in cell death pathways makes RIPK1 a potential target for therapeutic intervention. Furthermore, RIPK1 is involved in neurodegenerative disorders. Investigating RIPK1 provides insights into diverse physiological processes, offering avenues for developing treatments targeting cell death, inflammation, and related diseases.

Target Background

Function

Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways. Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival. Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway. Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis. RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis. In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1. Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis. Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8. In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6). Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Required for ZBP1-induced NF-kappa-B activation in response to DNA damage.

Gene References into Functions

The caspase 8 mediated RIPK1 cleavage product has a pro-apoptotic function, and further cleavage of this pro-apoptotic cleavage product by human rhinovirus 3C protease may provide a mechanism by which human rhinovirus limits apoptosis. PMID: 29371673
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
In lesional psoriatic epidermis, RIPK1-expression was decreased compared with that in normal epidermis. RIPK1-knockdown enhanced TRAIL-mediated expression of psoriasis-relating cytokines in normal human epidermal keratinocytes. PMID: 29661487
RIPK1 plays a critical role in the human immune system. PMID: 30026316
Elevated A20 promotes TNF-induced and RIPK1-dependent intestinal epithelial cell death PMID: 30209212
RIPK1-DD has a role in mediating RIPK1 dimerization and activation of its kinase activity during necroptosis and RIPK1-dependent apoptosis PMID: 29440439
We further identified this underlying mechanism also involved a PPARgamma-induced ANXA1-dependent autoubiquitination of cIAP1, the direct E3 ligase of RIP1, shifting cIAP1 toward proteosomal degradation..our study provides first insight for the suitability of using drug-induced expression of ANXA1 as a new player in RIP1-induced death machinery in triple-negative breast cancer PMID: 29021293
data suggest that artesunate could induce RIP1-dependent cell death in human renal carcinoma. PMID: 28466458
RIP1 has a role in CD40-mediated activation of caspase-8, which in turn leads to induction of apoptosis PMID: 28610909
High RIPK1 expression is associated with Alzheimer's disease. PMID: 28904096
These data represent the first report of decreased RIPK1 expression in neutrophils of Systemic Lupus Erythematosus patients and imply that RIPK1 may be involved in neutrophil death and neutrophil extracellular traps formation. PMID: 29550813
Data indicate that receptor (TNFRSF)-interacting serine-threonine kinase 1 (RIPK1) polymorphism is a prognostic biomarker for tumor development and survival of hepatocellular carcinoma (HCC) patients after hepatectomy. PMID: 28759952
Existence of a kinase-independent role of nuclear RIPK1 in the regulation of PARP1. PMID: 28993228
Study identify and quantify over 8,000 phosphorylated peptides, among which are numerous known sites in the TNF-RSC, NFkappaB, and MAP kinase signaling systems. Functional analysis of S320 phosphorylation in RIPK1 demonstrates a role for this event in suppressing its kinase activity, association with CASPASE-8 and FADD proteins, and subsequent necrotic cell death during inflammatory TNFalpha stimulation. PMID: 28539327
New potent RIPK1 inhibitors are reported (GSK2606414 and GSK2656157). PMID: 28452996
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
the cytoplasmic retinoic acid receptor gamma (RARgamma) controls receptor-interacting protein kinase 1 (RIP1)-initiated cell death when cellular inhibitor of apoptosis (cIAP) activity is blocked. PMID: 28871172
SIRT2 and RIPK1 were localized to the syncytiotrophoblast, villous leukocytes and vasculature in all preterm placentas. A significant reduction in SIRT2 protein expression in both preeclampsia and fetal growth restricted placentas was identified. RIPK1 mRNA expression was significantly increased in preeclampsia placentas. Immunofluorescence identified both SIRT2 and RIPK1 in the cytotrophoblast cytoplasm. PMID: 28292463
Results show that downregulation of RIP1 results in increased resistance to SN38, implying a requirement for RIP1 in mediating cytotoxicity through the TNF/TNFR signaling pathway. PMID: 28087739
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
Data suggest that pro-death signals through TIR-domain-containing adapter-inducing interferon-beta (TRIF) are regulated by autophagy and propose that pro-apoptotic signalling through TRIF/RIPK1/caspase-8 occurs in fibrillary platforms. PMID: 28453927
UL45 promoted the UL48-RIP1 interaction and re-localization of RIP1 to the UL48-containing virion assembly complex. PMID: 28570668
we provide evidence that p62 is implicated in the activation of NF-kappaB signaling that is partly dependent on RIP1 PMID: 28498503
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
Data show that pan-caspase inhibitors facilitated 5-fluorouracil (5-FU)-induced necroptosis mediated by secretion of tumor necrosis factor alpha (TNF-alpha) driven by nuclear factor kappaB (NF-kappaB) and required RIP1 kinase. PMID: 26522725
RIPK1 kinase activity is a pertinent therapeutic target to protect liver against excessive cell death in liver diseases. PMID: 27831558
Ripk1 is directly involved in apoptosis/necroptosis. In osteosarcoma cells( OS) , small interfering RNA against Ripk1 prevented cell death induced by the sequestration of miR-155-5p. Collectively, we show that miR-148a-3p and miR-155-5p are species-conserved deregulated miRNA in OS PMID: 27041566
RIPK1 collaborates with TRAF2 to inhibit murine and human hepatocarcinogenesis. PMID: 28017612
Necroptosis signaling is modulated by the kinase RIPK1 and requires the kinase RIPK3 and the pseudokinase MLKL. (Review) PMID: 26865533
CYLD Promotes TNF-alpha-Induced Cell Necrosis Mediated by RIP-1 in Human Lung Cancer Cells PMID: 27738385
TRAIL can enhance RIP1 and c-FLIPL expression in HepG2 cells. PMID: 28270653
Data indicate that RIP-1 promote the growth and invasion of gastric cancer in vitro and in vivo, additionally providing evidence that targeting RIP-1 may be useful in the treatment of gastric cancer. PMID: 27035122
High expression of RIP1 is associated with hepatocellular carcinoma. PMID: 27699664
The main route of cell death induced by shikonin is RIP1K-RIP3K-mediated necroptosis. PMID: 26496737
Upregulated expression of RIP1 is associated with triple-negative breast cancer. PMID: 27476169
Innate immune signaling through differential RIPK1 expression promote tumor progression in head and neck squamous cell carcinoma. PMID: 26992898
Positive significant correlation was found for RIP1K expression. PMID: 26749282
Hyperglycemic Conditions Prime Cells for RIP1-dependent Necroptosis. PMID: 27129772
In contrast, both necrostatin-1, a RIP1 kinase inhibitor, and Enbrel, a TNFalpha-blocking antibody, do not interfere with BV6/Drozitumab-induced apoptosis, demonstrating that apoptosis occurs independently of RIP1 kinase activity or an autocrine TNFalpha loop. PMID: 25880091
Report role of RIP1 in Smac mimetic mediated chemosensitization of neuroblastoma cells. PMID: 26575016
By promoting both inflammation and cell death, RIPK1 may be a common mediator of axonal pathology in amyotrophic lateral sclerosis. PMID: 27493188
Down-regulating RIP1 promotes oxaliplatin induced Tca8113 cells apoptosis PMID: 26460489
RIPK1 and RIPK2 are targets of HIV-1 Protease activity during infection, and their inactivation may contribute to modulation of cell death and host defense pathways by HIV-1 PMID: 26297639
These results identify upregulation of RIPK1 as an important resistance mechanism of melanoma cells to tunicamycin- or thapsigargin-induced endoplasmic reticulum stress. PMID: 26018731
CD40 ligand induces RIP1-dependent, necroptosis-like cell death in low-grade serous but not serous borderline ovarian tumor cells. PMID: 26313915
Data show that toll-like receptor 3/TRIF protein signalling regulates cytokines IL-32 and IFN-beta secretion by activation of receptor-interacting protein-1 (RIP-1) and tumour necrosis factor receptor-associated factor 6 (TRAF6) in cornea epithelial cells. PMID: 25754842
in the absence of caspase-8 activity, 24(S)-Hydroxycholesterol induces a necroptosis-like cell death which is RIPK1-dependent but MLKL-independent. PMID: 25697054
These data demonstrate that RIP1 is essential for the regulation of death receptor mediated autophagy and apoptosis. PMID: 25583602
a novel non-enzymatic function of AChE-R is to stimulate RIPK1/MLKL-dependent regulated necrosis (necroptosis). The latter complements a cholinergic system in the ovary, which determines life and death of ovarian cells. PMID: 25766324

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Subcellular Location

Cytoplasm. Cell membrane.

Protein Families

Protein kinase superfamily, TKL Ser/Thr protein kinase family

Database Links

HGNC: 10019

OMIM: 603453

KEGG: hsa:8737

STRING: 9606.ENSP00000259808

UniGene: Hs.519842

Code	CSB-EP618785HU2
Abbreviation	Recombinant Human RIPK1 protein, partial
MSDS	MSDS Datasheet
Size	$388
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Recombinant Human Receptor-interacting serine/threonine-protein kinase 1 (RIPK1), partial

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