产品描述
*The optimal dilutions should be determined by the end user.
*Tips:
WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.
引用格式: Affinity Biosciences Cat# AF2398, RRID:AB_2845412.
展开/折叠
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;
抗原和靶标
- Q13546 RIPK1_HUMAN:
- Protein BLAST With
- NCBI/
- ExPASy/
- Uniprot
MQPDMSLNVIKMKSSDFLESAELDSGGFGKVSLCFHRTQGLMIMKTVYKGPNCIEHNEALLEEAKMMNRLRHSRVVKLLGVIIEEGKYSLVMEYMEKGNLMHVLKAEMSTPLSVKGRIILEIIEGMCYLHGKGVIHKDLKPENILVDNDFHIKIADLGLASFKMWSKLNNEEHNELREVDGTAKKNGGTLYYMAPEHLNDVNAKPTEKSDVYSFAVVLWAIFANKEPYENAICEQQLIMCIKSGNRPDVDDITEYCPREIISLMKLCWEANPEARPTFPGIEEKFRPFYLSQLEESVEEDVKSLKKEYSNENAVVKRMQSLQLDCVAVPSSRSNSATEQPGSLHSSQGLGMGPVEESWFAPSLEHPQEENEPSLQSKLQDEANYHLYGSRMDRQTKQQPRQNVAYNREEERRRRVSHDPFAQQRPYENFQNTEGKGTAYSSAASHGNAVHQPSGLTSQPQVLYQNNGLYSSHGFGTRPLDPGTAGPRVWYRPIPSHMPSLHNIPVPETNYLGNTPTMPFSSLPPTDESIKYTIYNSTGIQIGAYNYMEIGGTSSSLLDSTNTNFKEEPAAKYQAIFDNTTSLTDKHLDPIRENLGKHWKNCARKLGFTQSQIDEIDHDYERDGLKEKVYQMLQKWVMREGIKGATVGKLAQALHQCSRIDLLSSLIYVSQN
翻译修饰 - Q13546 作为底物
Site | PTM Type | Enzyme | Source |
---|---|---|---|
Phosphorylation | Uniprot | ||
S6 | Phosphorylation | Uniprot | |
K13 | Ubiquitination | Uniprot | |
S14 | Phosphorylation | Q13546 (RIPK1) | Uniprot |
S15 | Phosphorylation | Q13546 (RIPK1) | Uniprot |
S20 | Phosphorylation | Q13546 (RIPK1) | Uniprot |
S25 | Phosphorylation | Uniprot | |
S32 | Phosphorylation | Uniprot | |
T38 | Phosphorylation | Uniprot | |
K49 | Ubiquitination | Uniprot | |
K105 | Ubiquitination | Uniprot | |
K115 | Ubiquitination | Uniprot | |
K137 | Ubiquitination | Uniprot | |
K140 | Ubiquitination | Uniprot | |
K153 | Ubiquitination | Uniprot | |
S161 | Phosphorylation | Q13546 (RIPK1) | Uniprot |
K163 | Ubiquitination | Uniprot | |
S166 | Phosphorylation | Q13546 (RIPK1) | Uniprot |
K167 | Ubiquitination | Uniprot | |
K184 | Ubiquitination | Uniprot | |
K185 | Ubiquitination | Uniprot | |
K284 | Ubiquitination | Uniprot | |
S296 | Phosphorylation | Uniprot | |
K302 | Ubiquitination | Uniprot | |
S303 | Phosphorylation | Uniprot | |
K306 | Ubiquitination | Uniprot | |
S309 | Phosphorylation | Uniprot | |
K316 | Ubiquitination | Uniprot | |
S320 | Phosphorylation | Uniprot | |
S330 | Phosphorylation | Uniprot | |
S331 | Phosphorylation | Uniprot | |
S333 | Phosphorylation | Uniprot | |
T337 | Phosphorylation | Uniprot | |
S346 | Phosphorylation | Uniprot | |
K377 | Ubiquitination | Uniprot | |
Y384 | Phosphorylation | Uniprot | |
Y387 | Phosphorylation | Uniprot | |
S389 | Phosphorylation | Uniprot | |
S416 | Phosphorylation | Uniprot | |
Y426 | Phosphorylation | Uniprot | |
Y463 | Phosphorylation | Uniprot | |
Y469 | Phosphorylation | Uniprot | |
S470 | Phosphorylation | Uniprot | |
S471 | Phosphorylation | Uniprot | |
R477 | Methylation | Uniprot | |
T483 | Phosphorylation | Uniprot | |
R487 | Methylation | Uniprot | |
Y490 | Phosphorylation | Uniprot | |
K530 | Acetylation | Uniprot | |
K571 | Ubiquitination | Uniprot | |
K585 | Ubiquitination | Uniprot | |
K596 | Ubiquitination | Uniprot | |
K604 | Ubiquitination | Uniprot | |
S610 | Phosphorylation | Uniprot | |
K627 | Ubiquitination | Uniprot | |
K642 | Acetylation | Uniprot | |
K642 | Ubiquitination | Uniprot | |
K648 | Acetylation | Uniprot | |
S664 | Phosphorylation | Uniprot |
翻译修饰 - Q13546 作为激酶
研究背景
Serine-threonine kinase which is a key regulator of both cell death and cell survival. Exhibits kinase activity-dependent functions that trigger cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival. Initiates ripoptocide which describes cell death that is dependent on RIPK1, be it apoptosis or necroptosis. 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-kB pathway (By similarity). Specific conditions can however activate RIPK1, and its kinase activity then regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8) and the complex IIb (RIPK1-RIPK3-MLKL) and these complexes respectively drive apoptosis or necroptosis, a regulated form of necrosis. During embryonic development suppresses apoptosis and necroptosis and prevents the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (By similarity). Phosphorylates DAB2IP at 'Ser-728' in a TNF- alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Required for ZBP1-induced NF-kappaB activation and activation of NF-kappaB by DNA damage and IR (By similarity).
Proteolytically cleaved by CASP8 at Asp-324. Cleavage is crucial for limiting apoptosis and necroptosis during embryonic development (By similarity). Cleavage abolishes NF-kappa-B activation and enhances the interaction of TRADD with FADD.
RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylation of Ser-161 by RIPK3 is necessary for the formation of the necroptosis-inducing complex. Phosphorylation at Ser-25 represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. 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 Ref.33). Polyubiquitination with 'Lys-63'-linked chains by TRAF2 induces association with the IKK complex. 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 NFkappa-B signaling. 'Lys-48'-linked polyubiquitination by RFFL or RNF34 also promotes proteasomal degradation and negatively regulates TNF-alpha-induced NF-kappa-B signaling Ref.33). Linear polyubiquitinated; the head-to-tail linear polyubiquitination ('Met-1'-linked) is mediated by the LUBAC complex and decreases protein kinase activity. 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. Ubiquitinated with 'Lys-63'-linked chains by PELI1. 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).
Cytoplasm. Cell membrane.
Homodimer. Interacts (via RIP homotypic interaction motif) with RIPK3 (via RIP homotypic interaction motif); this interaction induces RIPK1 phosphorylation and formation of a RIPK1-RIPK3 necroptosis-inducing complex. Upon TNF-induced necrosis, the RIPK1-RIPK3 dimer further interacts with PGAM5 and MLKL; the formation of this complex leads to PGAM5 phosphorylation and increase in PGAM5 phosphatase activity. Interacts (via the death domain) with TNFRSF6 (via the death domain) and TRADD (via the death domain). Is recruited by TRADD to TNFRSF1A in a TNF-dependent process. Binds RNF216, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3. Interacts with BNLF1. Interacts with SQSTM1 upon TNF-alpha stimulation. May interact with MAVS/IPS1. Interacts with ZFAND5. Interacts with RBCK1. Interacts with ZBP1 (By similarity). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts (via kinase domain) with DAB2IP (via Ras-GAP domain); the interaction occurs in a TNF-alpha-dependent manner. Interacts with ARHGEF2. Interacts (via protein kinase domain) with RFFL; involved in RIPK1 ubiquitination. Interacts with RNF34; involved in RIPK1 ubiquitination (Ref.33). Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1. Interacts with PELI1. Interacts (via death domain) with CRADD (via death domain); the interaction is direct. Component of complex IIa composed of at least RIPK1, FADD and CASP8 (By similarity). Interacts with MAP3K7, CFLAR, CASP8, FADD and NEMO (By similarity).
(Microbial infection) Interacts with mumps virus protein SH; this interaction inhibits downstream NF-kappa-B pathway activation.
(Microbial infection) Interacts with Murid herpesvirus 1 protein RIR1.
The death domain mediates dimerization and activation of its kinase activity during necroptosis and apoptosis (PubMed:29440439). It engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling (PubMed:10356400).
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
研究领域
· Cellular Processes > Cell growth and death > Apoptosis. (View pathway)
· Cellular Processes > Cell growth and death > Necroptosis. (View pathway)
· Environmental Information Processing > Signal transduction > NF-kappa B signaling pathway. (View pathway)
· Environmental Information Processing > Signal transduction > TNF signaling pathway. (View pathway)
· Human Diseases > Infectious diseases: Viral > Hepatitis C.
· Human Diseases > Infectious diseases: Viral > Epstein-Barr virus infection.
· Organismal Systems > Immune system > Toll-like receptor signaling pathway. (View pathway)
· Organismal Systems > Immune system > NOD-like receptor signaling pathway. (View pathway)
· Organismal Systems > Immune system > RIG-I-like receptor signaling pathway. (View pathway)
· Organismal Systems > Immune system > Cytosolic DNA-sensing pathway. (View pathway)
文献引用
Application: WB Species: Mouse Sample: skin tissues
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