InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RIPK3

Summary

InnateDB Protein

IDBP-3904.6

Last Modified

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

Gene Symbol

RIPK3

Protein Name

receptor-interacting serine-threonine kinase 3

Synonyms

RIP3;

Species

Homo sapiens

Ensembl Protein

ENSP00000216274

InnateDB Gene

IDBG-3902 (RIPK3)

Protein Structure

UniProt Annotation

Function

Essential for necroptosis, a programmed cell death process in response to death-inducing TNF-alpha family members. Upon induction of necrosis, RIPK3 interacts with, and phosphorylates RIPK1 and MLKL to form a necrosis-inducing complex. RIPK3 binds to and enhances the activity of three metabolic enzymes: GLUL, GLUD1, and PYGL. These metabolic enzymes may eventually stimulate the tricarboxylic acid cycle and oxidative phosphorylation, which could result in enhanced ROS production. {ECO:0000269PubMed:19498109, ECO:0000269PubMed:19524512, ECO:0000269PubMed:19524513, ECO:0000269PubMed:22265413, ECO:0000269PubMed:22265414, ECO:0000269PubMed:22421439}.

Subcellular Localization

Cytoplasm, cytosol {ECO:0000269PubMed:22265413}. Cell membrane {ECO:0000250}. Mitochondrion {ECO:0000305}.

Disease Associations

Tissue Specificity

Highly expressed in the pancreas. Detected at lower levels in heart, placenta, lung and kidney. Isoform 3 is significantly increased in colon and lung cancers. {ECO:0000269PubMed:15896315}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 28 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	28 [view]
Protein-Protein	28 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003713	transcription coactivator activity
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004704	NF-kappaB-inducing kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0032403	protein complex binding
GO:0042802	identical protein binding

Biological Process

GO:0001914	regulation of T cell mediated cytotoxicity
GO:0002224	toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0002819	regulation of adaptive immune response
GO:0006464	cellular protein modification process
GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0010922	positive regulation of phosphatase activity
GO:0032147	activation of protein kinase activity
GO:0032481	positive regulation of type I interferon production
GO:0032649	regulation of interferon-gamma production
GO:0033077	T cell differentiation in thymus
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0038061	NIK/NF-kappaB signaling
GO:0043029	T cell homeostasis
GO:0045087	innate immune response (InnateDB)
GO:0046006	regulation of activated T cell proliferation
GO:0046777	protein autophosphorylation
GO:0048535	lymph node development
GO:0048536	spleen development
GO:0048538	thymus development
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051260	protein homooligomerization
GO:0051291	protein heterooligomerization
GO:0051347	positive regulation of transferase activity
GO:0051351	positive regulation of ligase activity
GO:0051353	positive regulation of oxidoreductase activity
GO:0060545	positive regulation of necroptotic process
GO:0070235	regulation of activation-induced cell death of T cells
GO:0070266	necroptotic process
GO:0090312	positive regulation of protein deacetylation
GO:0097190	apoptotic signaling pathway
GO:1990000	amyloid fibril formation
GO:2000377	regulation of reactive oxygen species metabolic process
GO:2000379	positive regulation of reactive oxygen species metabolic process
GO:2000452	regulation of CD8-positive, alpha-beta cytotoxic T cell extravasation
GO:2001244	positive regulation of intrinsic apoptotic signaling pathway

Cellular Component

GO:0005622	intracellular
GO:0005739	mitochondrion
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0097342	ripoptosome

Protein Structure and Domains

PDB ID

InterPro

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
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt