RIPK1

Receptor (TNFRSF)-interacting serine-threonine kinase 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4ITH, 4ITI, 4ITJ, 4NEU
Identifiers
Symbols	RIPK1 ; RIP; RIP1
External IDs	OMIM: 603453 MGI: 108212 HomoloGene: 2820 IUPHAR: 2189 ChEMBL: 5464 GeneCards: RIPK1 Gene
EC number	2.7.11.1
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • death receptor binding • protein binding • ATP binding • ubiquitin protein ligase binding • protein complex binding • identical protein binding • death domain binding Cellular component • mitochondrion • cytosol • death-inducing signaling complex • receptor complex • membrane raft • ripoptosome Biological process • positive regulation of protein phosphorylation • toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • apoptotic process • activation of cysteine-type endopeptidase activity involved in apoptotic process • activation of JUN kinase activity • positive regulation of type I interferon production • positive regulation of interleukin-8 production • positive regulation of tumor necrosis factor production • tumor necrosis factor-mediated signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • response to tumor necrosis factor • TRIF-dependent toll-like receptor signaling pathway • peptidyl-serine autophosphorylation • positive regulation of apoptotic process • positive regulation of programmed cell death • positive regulation of I-kappaB kinase/NF-kappaB signaling • negative regulation of I-kappaB kinase/NF-kappaB signaling • cellular protein catabolic process • innate immune response • positive regulation of macrophage differentiation • positive regulation of transcription from RNA polymerase II promoter • positive regulation of JNK cascade • protein autophosphorylation • positive regulation of NF-kappaB transcription factor activity • protein homooligomerization • protein heterooligomerization • positive regulation of necroptotic process • T cell apoptotic process • necroptotic process • regulation of ATP:ADP antiporter activity • cellular response to tumor necrosis factor • apoptotic signaling pathway • extrinsic apoptotic signaling pathway • ripoptosome assembly • necroptotic signaling pathway • amyloid fibril formation • positive regulation of reactive oxygen species metabolic process • negative regulation of extrinsic apoptotic signaling pathway • positive regulation of extrinsic apoptotic signaling pathway • regulation of extrinsic apoptotic signaling pathway in absence of ligand • negative regulation of intrinsic apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8737	19766
Ensembl	ENSG00000137275	ENSMUSG00000021408
UniProt	Q13546	Q60855
RefSeq (mRNA)	NM_003804	NM_009068
RefSeq (protein)	NP_003795	NP_033094
Location (UCSC)	Chr 6: 3.06 – 3.12 Mb	Chr 13: 34 – 34.04 Mb
PubMed search

Receptor-interacting serine/threonine-protein kinase 1 is an enzyme that in humans is encoded by the RIPK1 gene.^[1][2][3] RIPK1 is known to have function in a variety of cellular pathways including the NF-κB pathway and programmed necrotic cell death (necroptosis).

Function

Although, RIPK1 has been primarily studied in the context of TNFR signaling, RIPk1 is also activated in response to diverse stimuli.^[4]

The kinase domain, while important for necroptotic (programmed necrotic) functions, it appears dispensable for pro-survival roles. Kinase activity of RIPK1 is also required for RIPK1-dependent apoptosis in conditions of IAP1/2 depletion, TAK1inhibition/depletion, RIPK3 depletion or MLKL depletion.^[5][6] Also, proteolytic processing of RIPk1, through both caspase-dependent and -independent mechanisms, triggers lethality that is dependent on the generation of one or more specific C-terminal cleavage product(s) of RIPk1 upon stress.

Interactions

RIPK1 has been shown to interact with:

• BIRC2,^[7]
• BIRC3,^[7]
• CA11,^[8]
• CASP8,^[7][9][10]
• CFLAR,^[9][11]
• CRADD,^[12][13]
• RIPK3,^[14][15]
• RNF11,^[16]
• RNF216,^[17]
• SQSTM1,^[18]
• TNFRSF1A,^{[2][12][19][20][21][22]}
• TRADD,^[2]
• TRAF2,^{[2][23][24][25]} and
• UBC.^{[7][8][21][22][26]}

References

Further reading