InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RIPK1

Summary

InnateDB Protein

IDBP-57328.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RIPK1

Protein Name

receptor (TNFRSF)-interacting serine-threonine kinase 1

Synonyms

RIP; RIP1;

Species

Homo sapiens

Ensembl Protein

ENSP00000369773

InnateDB Gene

IDBG-57326 (RIPK1)

Protein Structure

UniProt Annotation

Function

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. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. 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. 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. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex. {ECO:0000269PubMed:11101870, ECO:0000269PubMed:17389591, ECO:0000269PubMed:19524512, ECO:0000269PubMed:19524513}.

Subcellular Localization

Cytoplasm. Cell membrane {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 148 experimentally validated interaction(s) in this database.
They are also associated with 30 interaction(s) predicted by orthology.

Experimentally validated
Total	148 [view]
Protein-Protein	148 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	30 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005123	death receptor binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0031625	ubiquitin protein ligase binding
GO:0032403	protein complex binding
GO:0042802	identical protein binding
GO:0070513	death domain binding

Biological Process

GO:0001934	positive regulation of protein phosphorylation
GO:0002224	toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007165	signal transduction
GO:0007257	activation of JUN kinase activity
GO:0032481	positive regulation of type I interferon production
GO:0032757	positive regulation of interleukin-8 production
GO:0032760	positive regulation of tumor necrosis factor production
GO:0033209	tumor necrosis factor-mediated signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034612	response to tumor necrosis factor
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0036289	peptidyl-serine autophosphorylation
GO:0043065	positive regulation of apoptotic process
GO:0043068	positive regulation of programmed cell death
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043124	negative regulation of I-kappaB kinase/NF-kappaB signaling
GO:0044257	cellular protein catabolic process
GO:0045087	innate immune response (InnateDB)
GO:0045651	positive regulation of macrophage differentiation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046330	positive regulation of JNK cascade
GO:0046777	protein autophosphorylation
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051260	protein homooligomerization
GO:0051291	protein heterooligomerization
GO:0060545	positive regulation of necroptotic process
GO:0070231	T cell apoptotic process
GO:0070266	necroptotic process
GO:0070926	regulation of ATP:ADP antiporter activity
GO:0071356	cellular response to tumor necrosis factor
GO:0097190	apoptotic signaling pathway
GO:0097191	extrinsic apoptotic signaling pathway
GO:0097343	ripoptosome assembly
GO:0097527	necroptotic signaling pathway
GO:1990000	amyloid fibril formation
GO:2000379	positive regulation of reactive oxygen species metabolic process
GO:2001237	negative regulation of extrinsic apoptotic signaling pathway
GO:2001238	positive regulation of extrinsic apoptotic signaling pathway
GO:2001239	regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component

GO:0005739	mitochondrion
GO:0005829	cytosol
GO:0031264	death-inducing signaling complex
GO:0043235	receptor complex
GO:0097342	ripoptosome

Protein Structure and Domains

PDB ID

InterPro

IPR000488 Death domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011029 Death-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00531
PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00005
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt