InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RIPK2

Summary

InnateDB Protein

IDBP-27943.6

Last Modified

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

Gene Symbol

RIPK2

Protein Name

receptor-interacting serine-threonine kinase 2

Synonyms

CARD3; CARDIAK; CCK; GIG30; RICK; RIP2;

Species

Homo sapiens

Ensembl Protein

ENSP00000220751

InnateDB Gene

IDBG-27941 (RIPK2)

Protein Structure

UniProt Annotation

Function

Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation. {ECO:0000269PubMed:14638696, ECO:0000269PubMed:17054981, ECO:0000269PubMed:18079694, ECO:0000269PubMed:21123652, ECO:0000269PubMed:21887730}.

Subcellular Localization

Cytoplasm {ECO:0000305}.

Disease Associations

Tissue Specificity

Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas and lymph node.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 86 experimentally validated interaction(s) in this database.
They are also associated with 10 interaction(s) predicted by orthology.

Experimentally validated
Total	86 [view]
Protein-Protein	84 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	10 [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:0004715	non-membrane spanning protein tyrosine kinase activity
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0030274	LIM domain binding
GO:0042803	protein homodimerization activity
GO:0050700	CARD domain binding

Biological Process

GO:0000187	activation of MAPK activity
GO:0001961	positive regulation of cytokine-mediated signaling pathway
GO:0002224	toll-like receptor signaling pathway
GO:0002250	adaptive immune response
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0002827	positive regulation of T-helper 1 type immune response
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0007254	JNK cascade
GO:0010800	positive regulation of peptidyl-threonine phosphorylation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0031398	positive regulation of protein ubiquitination
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0032722	positive regulation of chemokine production
GO:0032727	positive regulation of interferon-alpha production
GO:0032728	positive regulation of interferon-beta production
GO:0032729	positive regulation of interferon-gamma production
GO:0032735	positive regulation of interleukin-12 production
GO:0032743	positive regulation of interleukin-2 production
GO:0032755	positive regulation of interleukin-6 production
GO:0032760	positive regulation of tumor necrosis factor production
GO:0032874	positive regulation of stress-activated MAPK cascade
GO:0033091	positive regulation of immature T cell proliferation
GO:0033138	positive regulation of peptidyl-serine phosphorylation
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0042098	T cell proliferation
GO:0042981	regulation of apoptotic process
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043330	response to exogenous dsRNA
GO:0045087	innate immune response (InnateDB)
GO:0045627	positive regulation of T-helper 1 cell differentiation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046330	positive regulation of JNK cascade
GO:0046641	positive regulation of alpha-beta T cell proliferation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation
GO:0050830	defense response to Gram-positive bacterium
GO:0050852	T cell receptor signaling pathway
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051403	stress-activated MAPK cascade
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0070423	nucleotide-binding oligomerization domain containing signaling pathway
GO:0070427	nucleotide-binding oligomerization domain containing 1 signaling pathway
GO:0070431	nucleotide-binding oligomerization domain containing 2 signaling pathway
GO:0070555	response to interleukin-1
GO:0070671	response to interleukin-12
GO:0070673	response to interleukin-18
GO:0071222	cellular response to lipopolysaccharide
GO:0071223	cellular response to lipoteichoic acid
GO:0071224	cellular response to peptidoglycan
GO:0071225	cellular response to muramyl dipeptide

Cellular Component

GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005856	cytoskeleton
GO:0031982	vesicle
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR001315 CARD domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011029 Death-like domain
IPR017322 Receptor-interacting serine/threonine-protein kinase 2
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF00619

PRINTS

PR00109

PIRSF

PIRSF037921

SMART

SM00114
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References