Rabbit Anti-RIPK1 Recombinant Antibody (D94C12) (CBMAB-R2723-CN)

Rabbit

Human, Mouse, Rat, Hamster, Monkey

D94C12

WB, IP, IF, FC

Human, Mouse, Rat, Hamster, Monkey

Monoclonal

The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Receptor Interacting Serine/Threonine Kinase 1

This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein plays a role in inflammation and cell death in response to tissue damage, pathogen recognition, and as part of developmental regulation. RIPK1/RIPK3 kinase-mediated necrosis is referred to as necroptosis. Genetic disruption of this gene in mice results in death shortly after birth. [provided by RefSeq, Aug 2017]

Receptor Interacting Serine/Threonine Kinase 1; Receptor (TNFRSF)-Interacting Serine-Threonine Kinase 1; Receptor-Interacting Protein Kinase 1; Serine/Threonine-Protein Kinase RIP; Receptor-Interacting Protein 1; Cell Death Protein RIP;

Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways (PubMed:32657447, PubMed:31827280, PubMed:31827281).
Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:11101870, PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283).
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 (By similarity).
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 (By similarity).
RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis (By similarity).
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 (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283).
Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283).
Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (By similarity).
In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) (PubMed:31827280, PubMed:31827281).
Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (PubMed:19524513).
Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (PubMed:17389591, PubMed:15310755).
Required for ZBP1-induced NF-kappa-B activation in response to DNA damage (By similarity).

Biological Process amyloid fibril formationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cell deathManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cellular response to growth factor stimulusIEA:Ensembl
Biological Process cellular response to hydrogen peroxideISS:ARUK-UCL
Biological Process cellular response to tumor necrosis factorManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process inflammatory responseIEA:UniProtKB-KW
Biological Process necroptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process necroptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of apoptotic processISS:UniProtKB
Biological Process negative regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of extrinsic apoptotic signaling pathway in absence of ligandIEA:Ensembl
Biological Process negative regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of necroptotic processISS:UniProtKB
Biological Process peptidyl-serine autophosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of hydrogen peroxide-induced cell deathManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of inflammatory responseManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of interleukin-6-mediated signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of interleukin-8 productionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of JNK cascadeManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of macrophage differentiationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of miRNA maturationManual Assertion Based On ExperimentIDA:ARUK-UCL
Biological Process positive regulation of necroptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of necrotic cell deathManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of programmed cell deathManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of protein phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process positive regulation of reactive oxygen species metabolic processManual Assertion Based On ExperimentTAS:BHF-UCL
Biological Process positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of tumor necrosis factor-mediated signaling pathwayIEA:Ensembl
Biological Process programmed necrotic cell deathISS:ARUK-UCL
Biological Process protein autophosphorylationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process protein catabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of ATP:ADP antiporter activityManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process response to tumor necrosis factorManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process ripoptosome assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process ripoptosome assembly involved in necroptotic processIEA:Ensembl
Biological Process T cell apoptotic processISS:UniProtKB
Biological Process tumor necrosis factor-mediated signaling pathway1 PublicationIC:BHF-UCL

Cytoplasm
Cell membrane

(Microbial infection) Proteolytically cleaved by S.flexneri OspD3 within the RIP homotypic interaction motif (RHIM), leading to its degradation and inhibition of necroptosis.
Proteolytically cleaved by CASP8 at Asp-324 (PubMed:10521396, PubMed:31827281, PubMed:31827280).
Cleavage is crucial for limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827281, PubMed:31827280).
Cleavage abolishes NF-kappa-B activation and enhances the interaction of TRADD with FADD (PubMed:10521396).
Proteolytically cleaved by CASP6 during intrinsic apoptosis (PubMed:22858542).
RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (PubMed:18408713, PubMed:19524513, PubMed:31827280).
Phosphorylation of Ser-161 by RIPK3 is necessary for the formation of the necroptosis-inducing complex (PubMed:18408713).
Phosphorylation at Ser-25 represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (PubMed:30988283).
Phosphorylated at Ser-320 by MAP3K7 which requires prior ubiquitination with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 (By similarity).
This phosphorylation positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity).
Ubiquitinated with 'Lys-11'-, 'Lys-48'-, 'Lys-63'- and linear-linked type ubiquitin (PubMed:15258597, PubMed:16603398, PubMed:18450452, PubMed:21455173, PubMed:21931591, PubMed:29883609, Ref.34). Polyubiquitination with 'Lys-63'-linked chains by TRAF2 induces association with the IKK complex (PubMed:15258597).
Deubiquitination of 'Lys-63'-linked chains and polyubiquitination with 'Lys-48'-linked chains by TNFAIP3 leads to RIPK1 proteasomal degradation and consequently down-regulates TNF-alpha-induced NF-kappa-B signaling (PubMed:15258597).
'Lys-48'-linked polyubiquitination by RFFL or RNF34 also promotes proteasomal degradation and negatively regulates TNF-alpha-induced NF-kappa-B signaling (PubMed:18450452, Ref.34). Linear polyubiquitinated; the head-to-tail linear polyubiquitination ('Met-1'-linked) is mediated by the LUBAC complex and decreases protein kinase activity (PubMed:21455173).
Deubiquitination of linear polyubiquitin by CYLD promotes the kinase activity (By similarity).
Polyubiquitinated with 'Lys-48' and 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B (PubMed:21931591).
Ubiquitinated with 'Lys-63'-linked chains by PELI1 (PubMed:29883609).
Ubiquitination at Lys-377 with 'Lys-63'-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2 is essential for its phosphorylation at Ser-320 mediated by MAP3K7 (By similarity).
This ubiquitination is required for NF-kB activation, suppresses RIPK1 kinase activity and plays a critical role in preventing cell death during embryonic development (By similarity).
(Microbial infection) Glycosylated at Arg-603 by enteropathogenic E.coli protein NleB1: arginine GlcNAcylation prevents homotypic/heterotypic death domain interactions.