Tchem RIPK1 Receptor-interacting serine/threonine-protein kinase 1

Protein Summary

Description

Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage (PubMed:11101870, PubMed:17389591, PubMed:19524512, PubMed:19524513). Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor (PubMed:11101870, PubMed:17389591, PubMed:19524512, PubMed:19524513). Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (PubMed:17389591). Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules (PubMed:15258597). Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death (PubMed:15258597). RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex (PubMed:19524513, PubMed:19524512). 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]

Uniprot Accession IDs

• Q13546
• A0AV89
• B2RAG1
• B4E3F9
• Q13180
• Q59H33

Gene Name

• RIPK1

Ensembl ID

• ENST00000259808
• ENSP00000259808
• ENSG00000137275
• ENST00000380409
• ENSP00000369773

Symbol

• RIP
• RIP1
• RIP
• RIP1
• IMD57
• RIP-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	0.99
molecular function	0.99
virus perturbation	0.98
protein domain	0.92

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tkl Group / Ripk Family / Receptor-interacting Serine/threonine-protein Kinase 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 702.07   (req: < 5)

Gene RIFs: 248   (req: <= 3)

Antibodies: 543   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 702.07   (req: >= 5)

Gene RIFs: 248   (req: > 3)

Antibodies: 543   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 59

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 153

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1