| URN | urn:agi-llid:8737 |
|---|---|
| Total Entities | 0 |
| Connectivity | 507 |
| Name | Ripk1 |
| Description | receptor (TNFRSF)-interacting serine-threonine kinase 1 (predicted) |
| Notes | Activation of IKK by TNF-alpha requires site-specific ubiquitination of RIP1. Activation of IKK by TNF-alpha requires site-specific ubiquitination of RIP1. FAK overexpression in human tumors provides a survival signal function by binding to RIP and inhibiting its interaction with the death receptor complex. RIP is one of the critical components involved in mediating DNA damage-induced, p53-independent cell death. RIP may serve as a general activator of IRF7, responding to and transmitting the signals from various stimuli, and that ubiquitination may be a general mechanism for enhancing the activity of IRF7. TAK1 is recruited to the TNF-R1 complex via RIP and likely cooperates with MEKK3 to activate NF-kappaB in TNF-alpha signaling. TNF-induced TRAF2-RIP1-AIP1-ASK1 complex formation and for the activation of ASK1-JNK/p38 apoptotic signaling. The expression of receptor-interacting protein 1 (RIP1) in peripheral blood mononuclear cells was significantly decreased in SLE patients. This study provides the first genetic evidence that the ubiquitination of RIP is required for TNFalpha-induced NF-kappaB activation. We describe how RIP1 acts as a key integrator of signalling pathways initiated by stimulation of death receptors, bacterial or viral infection, genotoxic stress and T-cell homeostasis. Cells pre-stimulated through TNFR-2 prior to subsequent activation of TNFR-1, showed enhanced cell death and recruitment of RIP to the TNFR-1 complex; deficiency of RIP rescued the infected cells from TNF-induced cytotoxicity. Findings show ubiquitination of RIP1 inhibits TNF-induced apoptosis first through an NF-kappaB-independent mechanism, then through an NF-kappaB-dependent mechanism; in absence of ubiquitination, RIP1 serves as a proapoptotic signaling molecule. |
| Ariadne Ontology | TNFRAP |
|---|---|
| Secreted proteins |
| GO Molecular Function | death receptor binding |
|---|---|
| death domain binding | |
| nucleotide binding | |
| ATP binding | |
| transferase activity | |
| transferase activity, transferring phosphorus-containing groups | |
| kinase activity | |
| protein kinase activity | |
| protein serine-threonine kinase activity |
| GO Cellular Component | membrane |
|---|---|
| endosome membrane | |
| membrane raft | |
| death-inducing signaling complex | |
| protein complex | |
| receptor complex | |
| plasma membrane | |
| cytoplasm | |
| mitochondrion | |
| cytosol |
| GO Biological Process | virus-host interaction |
|---|---|
| negative regulation of intrinsic apoptotic signaling pathway | |
| negative regulation of extrinsic apoptotic signaling pathway | |
| positive regulation of I-kappaB kinase-NF-kappaB cascade | |
| positive regulation of extrinsic apoptotic signaling pathway | |
| activation of JUN kinase activity | |
| signal transduction | |
| apoptotic signaling pathway | |
| toll-like receptor 3 signaling pathway | |
| toll-like receptor 4 signaling pathway | |
| MyD88-independent toll-like receptor signaling pathway | |
| TRIF-dependent toll-like receptor signaling pathway | |
| Toll signaling pathway | |
| tumor necrosis factor-mediated signaling pathway | |
| positive regulation of reactive oxygen species metabolic process | |
| positive regulation of transcription from RNA polymerase II promoter | |
| positive regulation of phosphorylation | |
| positive regulation of NF-kappaB transcription factor activity | |
| positive regulation of necrotic cell death | |
| positive regulation of programmed cell death | |
| positive regulation of necroptosis | |
| induction of necroptosis by extracellular signals | |
| positive regulation of apoptotic process | |
| induction of apoptosis | |
| activation of cysteine-type endopeptidase activity involved in apoptotic process | |
| regulation of ATP:ADP antiporter activity | |
| protein phosphorylation | |
| protein autophosphorylation | |
| phosphorylation | |
| apoptotic process | |
| innate immune response | |
| response to tumor necrosis factor | |
| positive regulation of interleukin-8 production | |
| positive regulation of tumor necrosis factor production | |
| positive regulation of type I interferon production | |
| protein heterooligomerization | |
| protein homooligomerization |
| Pathway | Apoptosis |
|---|---|
| Toll-like receptor signaling pathway | |
| tumor necrosis factor signaling pathway | |
| tumor necrosis factor mediated signaling pathway | |
| ripk2-Xiap | |
| tumor necrosis factor signaling pathway | |
| tumor necrosis factor mediated signaling pathway |
| Group | TNFRAP |
|---|---|
| virus-host interaction | |
| negative regulation of intrinsic apoptotic signaling pathway | |
| negative regulation of extrinsic apoptotic signaling pathway | |
| positive regulation of I-kappaB kinase-NF-kappaB cascade | |
| positive regulation of extrinsic apoptotic signaling pathway | |
| activation of JUN kinase activity | |
| signal transduction | |
| apoptotic signaling pathway | |
| toll-like receptor 3 signaling pathway | |
| toll-like receptor 4 signaling pathway | |
| MyD88-independent toll-like receptor signaling pathway | |
| TRIF-dependent toll-like receptor signaling pathway | |
| Toll signaling pathway | |
| tumor necrosis factor-mediated signaling pathway | |
| positive regulation of reactive oxygen species metabolic process | |
| positive regulation of transcription from RNA polymerase II promoter | |
| positive regulation of phosphorylation | |
| positive regulation of NF-kappaB transcription factor activity | |
| positive regulation of necrotic cell death | |
| positive regulation of programmed cell death | |
| positive regulation of necroptosis | |
| induction of necroptosis by extracellular signals | |
| positive regulation of apoptotic process | |
| induction of apoptosis | |
| activation of cysteine-type endopeptidase activity involved in apoptotic process | |
| regulation of ATP:ADP antiporter activity | |
| protein phosphorylation | |
| protein autophosphorylation | |
| phosphorylation | |
| apoptotic process | |
| innate immune response | |
| response to tumor necrosis factor | |
| positive regulation of interleukin-8 production | |
| positive regulation of tumor necrosis factor production | |
| positive regulation of type I interferon production | |
| protein heterooligomerization | |
| protein homooligomerization | |
| death receptor binding | |
| death domain binding | |
| nucleotide binding | |
| ATP binding | |
| transferase activity | |
| transferase activity, transferring phosphorus-containing groups | |
| kinase activity | |
| protein kinase activity | |
| protein serine-threonine kinase activity | |
| membrane | |
| endosome membrane | |
| membrane raft | |
| death-inducing signaling complex | |
| protein complex | |
| receptor complex | |
| plasma membrane | |
| cytoplasm | |
| mitochondrion | |
| cytosol | |
| Secreted proteins |
| Source | Curated |
|---|---|
| ResNet |
| MedScan ID | 8737 |
|---|
| Hugo ID | 10019 |
|---|
| Human chromosome position | 6p25.2 |
|---|
| LocusLink ID | 8737 |
|---|---|
| 19766 | |
| 306886 | |
| 328217 | |
| 504727 | |
| 567460 |
| Alias | RIP |
|---|---|
| RIP1 | |
| receptor-interacting serine/threonine-protein kinase 1 | |
| RIP-1 | |
| cell death protein RIP | |
| receptor interacting protein | |
| receptor-interacting protein 1 | |
| serine/threonine-protein kinase RIP | |
| Rinp | |
| D330015H01Rik | |
| TNFRSF interacting protein | |
| Ripk I | |
| Serine/threonine protein kinase RIP | |
| receptor (TNFRSF)-interacting serine-threonine kinase 1 | |
| TNFRSF-interacting protein | |
| Ripk1 | |
| receptor (TNFRSF)-interactive serine-threonine kinase I | |
| receptor (TNFRSF)-interacting serine-threonine kinase I | |
| OTTHUMP00000039163 | |
| OTTHUMP00000015955 | |
| FLJ39204 | |
| D330015H01 | |
| receptor (TNFRSF)-interactive serine-threonine kinase 1 | |
| Cell death protein RIP | |
| RIKEN cDNA D330015H01 gene | |
| receptor (TNFRSF)-interacting serine-threonine kinase 1 (predicted) | |
| chromosome | |
| receptor-interacting 1 | |
| scaffold | |
| si:ch211-241e1.1 |
| Organism | Homo sapiens |
|---|---|
| Mus musculus | |
| Rattus norvegicus | |
| Bos taurus | |
| Danio rerio |
| OMIM ID | 603453 |
|---|
| Unigene ID | Hs.519842 |
|---|---|
| Mm.374799 | |
| Rn.7572 | |
| Hs.576620 | |
| Bt.6302 | |
| Dr.103967 |
| KEGG ID | hsa:8737 |
|---|---|
| mmu:19766 | |
| rno:306886 |
| Swiss-Prot Accession | Q13546 |
|---|---|
| Q60855 | |
| D3ZYL0 | |
| A0AV89 | |
| B2RAG1 | |
| B4E3F9 | |
| Q13180 | |
| Q59H33 | |
| Q3U0J3 | |
| Q8CD90 |
| EC Number | 2.7.11.1 |
|---|
| GO ID | 0005524 |
|---|---|
| 0070513 | |
| 0005123 | |
| 0004672 | |
| 0004674 | |
| 0002756 | |
| 0035666 | |
| 0008063 | |
| 0007257 | |
| 0006919 | |
| 0008633 | |
| 0006915 | |
| 0006917 | |
| 0060555 | |
| 0045087 | |
| 2001237 | |
| 2001243 | |
| 0043123 | |
| 0051092 | |
| 0043065 | |
| 2001238 | |
| 0032757 | |
| 0060545 | |
| 0010940 | |
| 0043068 | |
| 2000379 | |
| 0045944 | |
| 0032760 | |
| 0032481 | |
| 0046777 | |
| 0051260 | |
| 0070926 | |
| 0034612 | |
| 0007165 | |
| 0034138 | |
| 0034142 | |
| 0033209 | |
| 0005737 | |
| 0005829 | |
| 0031264 | |
| 0010008 | |
| 0045121 | |
| 0005739 | |
| 0043235 | |
| 0016301 | |
| 0000166 | |
| 0016740 | |
| 0016772 | |
| 0016310 | |
| 0042327 | |
| 0051291 | |
| 0006468 | |
| 0019048 | |
| 0016020 | |
| 0005886 | |
| 0043234 | |
| 0008624 | |
| 0045768 | |
| 0007249 | |
| 0080010 | |
| 0004872 | |
| 0005515 | |
| 0004713 | |
| 0004871 |
| PIR ID | T09479 |
|---|---|
| I49299 |
| Swiss-Prot ID | RIPK1_HUMAN |
|---|---|
| RIPK1_MOUSE |
| Cell Localization | Cytoplasm |
|---|---|
| Cell membrane |
| IPI ID | IPI00013773 |
|---|---|
| IPI00939198 | |
| IPI00121472 | |
| IPI00366094 |
| Mouse chromosome position | 13 13.9 cM |
|---|
| Rat chromosome position | 17p12 |
|---|
| Homologene ID | 2820 |
|---|
| MGI ID | 108212 |
|---|---|
| 2442778 |
| RGD ID | 1310158 |
|---|
| Primary Cell Localization | Cytoplasm |
|---|
| Homo sapiens Chromosome position | 6p25.2 |
|---|
| Microarray ID | 97091_at |
|---|---|
| 1419508_at | |
| 1439273_at | |
| 1449485_at |
| FunctionalClass | ATP binding |
|---|---|
| nucleotide binding | |
| protein binding | |
| protein serine/threonine kinase | |
| protein-tyrosine kinase | |
| signal transducer | |
| transferase | |
| kinase | |
| protein kinase | |
| receptor |
| Mus musculus Chromosome position | 13 13.9 cM |
|---|---|
| 13 A3.3 |
| KEGG pathway | Apoptosis |
|---|
| Rattus norvegicus Chromosome position | 17p12 |
|---|
| Bos taurus Chromosome position | 23 |
|---|