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Aliases for RIPK2 Gene

Aliases for RIPK2 Gene

  • Receptor Interacting Serine/Threonine Kinase 2 2 3 5
  • Receptor-Interacting Serine-Threonine Kinase 2 2 3
  • CARD-Containing IL-1 Beta ICE-Kinase 3 4
  • Receptor-Interacting Protein 2 3 4
  • Tyrosine-Protein Kinase RIPK2 3 4
  • EC 2.7.11.1 4 63
  • CARDIAK 3 4
  • RIP-2 3 4
  • RIP2 3 4
  • RICK 3 4
  • Receptor-Interacting Protein (RIP)-Like Interacting Caspase-Like Apoptosis Regulatory Protein (CLARP) Kinase 3
  • CARD-Containing Interleukin-1 Beta-Converting Enzyme (ICE)-Associated Kinase 3
  • CARD-Containing Interleukin-1 Beta-Converting Enzyme-Associated Kinase 4
  • RIP-Like-Interacting CLARP Kinase 4
  • Growth-Inhibiting Gene 30 3
  • CARD-Carrying Kinase 3
  • EC 2.7.10.2 4
  • EC 2.7.11 63
  • CARD3 3
  • GIG30 3
  • CCK 3

External Ids for RIPK2 Gene

Previous GeneCards Identifiers for RIPK2 Gene

  • GC08P089201
  • GC08P090502
  • GC08P090726
  • GC08P090839
  • GC08P085980
  • GC08P090769

Summaries for RIPK2 Gene

Entrez Gene Summary for RIPK2 Gene

  • This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein contains a C-terminal caspase activation and recruitment domain (CARD), and is a component of signaling complexes in both the innate and adaptive immune pathways. It is a potent activator of NF-kappaB and inducer of apoptosis in response to various stimuli. [provided by RefSeq, Jul 2008]

GeneCards Summary for RIPK2 Gene

RIPK2 (Receptor Interacting Serine/Threonine Kinase 2) is a Protein Coding gene. Among its related pathways are Signaling by GPCR and Immune System. GO annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is RIPK3.

UniProtKB/Swiss-Prot for RIPK2 Gene

  • 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.

Gene Wiki entry for RIPK2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RIPK2 Gene

Genomics for RIPK2 Gene

Regulatory Elements for RIPK2 Gene

Promoters for RIPK2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around RIPK2 on UCSC Golden Path with GeneCards custom track

Genomic Location for RIPK2 Gene

Chromosome:
8
Start:
89,757,733 bp from pter
End:
89,791,064 bp from pter
Size:
33,332 bases
Orientation:
Plus strand

Genomic View for RIPK2 Gene

Genes around RIPK2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RIPK2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RIPK2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RIPK2 Gene

Proteins for RIPK2 Gene

  • Protein details for RIPK2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43353-RIPK2_HUMAN
    Recommended name:
    Receptor-interacting serine/threonine-protein kinase 2
    Protein Accession:
    O43353
    Secondary Accessions:
    • B7Z748
    • Q6UWF0

    Protein attributes for RIPK2 Gene

    Size:
    540 amino acids
    Molecular mass:
    61195 Da
    Quaternary structure:
    • Found in a signaling complex consisting of at least ARHGEF2, NOD2 and RIPK2. Interacts with ARHGEF2; the interaction mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK. Binds to CFLAR/CLARP and CASP1 via their CARD domains. Binds to BIRC3/c-IAP1 and BIRC2/c-IAP2, TRAF1, TRAF2, TRAF5 and TRAF6. May be a component of both the TNFRSF1A and TNRFSF5/CD40 receptor complex. Interacts with NOD1. Interacts (via CARD domain) with NOD2 (via CARD domain). Interacts with MAP3K4; this interaction sequesters RIPK2 from the NOD2 signaling pathway. Interacts with IKBKG/NEMO. The polyubiquitinated protein interacts with MAP3K7/TAK1. Interacts with XIAP/BIRC4. Interacts with NLRP10. Interacts with CARD9.

    Three dimensional structures from OCA and Proteopedia for RIPK2 Gene

    Alternative splice isoforms for RIPK2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RIPK2 Gene

Proteomics data for RIPK2 Gene at MOPED

Selected DME Specific Peptides for RIPK2 Gene

Post-translational modifications for RIPK2 Gene

  • Autophosphorylated. Autophosphorylation at Tyr-474 is necessary for effective NOD2 signaling. Phosphorylated. Phosphorylation at Tyr-381 by Src kinase CSK occurs in a ARHGEF2-dependent manner and is required for NOD2-dependent innate immune activation.
  • Ubiquitinated on Lys-209; undergoes Lys-63-linked polyubiquitination catalyzed by ITCH. Polyubiquitinated with Lys-48 and Lys-63-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B. Also undergoes Met-1-linked polyubiquitination; the head-to-tail linear polyubiquitination is mediated by the LUBAC complex in response to NOD2 stimulation. Linear polyubiquitination is restricted by FAM105B/otulin, probably to limit NOD2-dependent proinflammatory signaling activation of NF-kappa-B.
  • Ubiquitination at Lys 209
  • Modification sites at PhosphoSitePlus

Other Protein References for RIPK2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for RIPK2 (RIPK2)

Domains & Families for RIPK2 Gene

Suggested Antigen Peptide Sequences for RIPK2 Gene

Graphical View of Domain Structure for InterPro Entry

O43353

UniProtKB/Swiss-Prot:

RIPK2_HUMAN :
  • Contains an N-terminal kinase domain and a C-terminal caspase activation and recruitment domain (CARD) that mediates the recruitment of CARD-containing proteins.
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Domain:
  • Contains an N-terminal kinase domain and a C-terminal caspase activation and recruitment domain (CARD) that mediates the recruitment of CARD-containing proteins.
  • Contains 1 CARD domain.
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
genes like me logo Genes that share domains with RIPK2: view

Function for RIPK2 Gene

Molecular function for RIPK2 Gene

GENATLAS Biochemistry:
receptor interacting serine-threonine kinase 2,widely expressed with two transcripts due to differential polyadenylation,regulator of TNFRSF6 (CD95)-mediated
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for RIPK2 Gene

genes like me logo Genes that share phenotypes with RIPK2: view

Animal Models for RIPK2 Gene

MGI Knock Outs for RIPK2:

Animal Model Products

CRISPR Products

miRNA for RIPK2 Gene

miRTarBase miRNAs that target RIPK2

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Gene Ontology (GO) - Molecular Function , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RIPK2 Gene

Localization for RIPK2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RIPK2 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for RIPK2 Gene COMPARTMENTS Subcellular localization image for RIPK2 gene
Compartment Confidence
cytoskeleton 5
cytosol 5
nucleus 3

No data available for Gene Ontology (GO) - Cellular Components for RIPK2 Gene

Pathways & Interactions for RIPK2 Gene

SuperPathways for RIPK2 Gene

Superpath Contained pathways
1 MyD88 cascade initiated on plasma membrane
2 Interleukin-3, 5 and GM-CSF signaling
3 Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
4 Signaling by GPCR
5 Immune System
genes like me logo Genes that share pathways with RIPK2: view

SIGNOR curated interactions for RIPK2 Gene

Activates:
Other effect:

Gene Ontology (GO) - Biological Process for RIPK2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000187 activation of MAPK activity TAS --
GO:0001961 positive regulation of cytokine-mediated signaling pathway IEA --
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002250 adaptive immune response IEA,ISS --
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with RIPK2: view

Drugs & Compounds for RIPK2 Gene

(6) Drugs for RIPK2 Gene - From: HMDB, Novoseek, and DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
SRC KINASE INHIBITOR I Pharma 0

(1) Additional Compounds for RIPK2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
genes like me logo Genes that share compounds with RIPK2: view

Transcripts for RIPK2 Gene

Unigene Clusters for RIPK2 Gene

Receptor-interacting serine-threonine kinase 2:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for RIPK2 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b
SP1: -
SP2: - - -
SP3:

Relevant External Links for RIPK2 Gene

GeneLoc Exon Structure for
RIPK2
ECgene alternative splicing isoforms for
RIPK2

Expression for RIPK2 Gene

mRNA expression in normal human tissues for RIPK2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for RIPK2 Gene

This gene is overexpressed in Plasma (24.0), Peripheral blood mononuclear cells (10.1), Placenta (6.5), and Islet of Langerhans (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for RIPK2 Gene



SOURCE GeneReport for Unigene cluster for RIPK2 Gene Hs.103755

mRNA Expression by UniProt/SwissProt for RIPK2 Gene

O43353-RIPK2_HUMAN
Tissue specificity: Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas and lymph node.
genes like me logo Genes that share expression patterns with RIPK2: view

Protein tissue co-expression partners for RIPK2 Gene

- Elite partner

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for RIPK2 Gene

Orthologs for RIPK2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for RIPK2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RIPK2 35
  • 99.69 (n)
  • 99.44 (a)
RIPK2 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia RIPK2 36
  • 81 (a)
OneToOne
RIPK2 35
  • 89.08 (n)
  • 87.52 (a)
dog
(Canis familiaris)
Mammalia RIPK2 35
  • 89.78 (n)
  • 86.99 (a)
RIPK2 36
  • 87 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Ripk2 16
Ripk2 35
  • 85.16 (n)
  • 84.42 (a)
Ripk2 36
  • 84 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia RIPK2 36
  • 75 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 78 (a)
OneToMany
-- 36
  • 64 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Ripk2 35
  • 84.85 (n)
  • 85.16 (a)
chicken
(Gallus gallus)
Aves RIPK2 35
  • 70.42 (n)
  • 69.32 (a)
RIPK2 36
  • 65 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RIPK2 36
  • 62 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ripk2 35
  • 62.02 (n)
  • 59.19 (a)
zebrafish
(Danio rerio)
Actinopterygii ripk2 36
  • 48 (a)
OneToOne
ripk2 35
  • 56.31 (n)
  • 53.6 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 24 (a)
ManyToMany
Species with no ortholog for RIPK2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for RIPK2 Gene

ENSEMBL:
Gene Tree for RIPK2 (if available)
TreeFam:
Gene Tree for RIPK2 (if available)

Paralogs for RIPK2 Gene

Paralogs for RIPK2 Gene

genes like me logo Genes that share paralogs with RIPK2: view

Variants for RIPK2 Gene

Sequence variations from dbSNP and Humsavar for RIPK2 Gene

SNP ID Clin Chr 08 pos Sequence Context AA Info Type
rs2230801 - 89,772,751(+) TGATA(C/T)ACCTC reference, missense
rs35004667 - 89,772,777(+) TCTCT(C/G/T)TAATA reference, missense
rs35395048 - 89,780,160(+) ACAAA(C/G/T)GTAAG reference, missense
rs39503 -- 89,767,579(+) TAGAA(A/G)TACCT intron-variant
rs39507 -- 89,781,580(+) TTTTT(A/T)AAAAA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RIPK2 Gene

Variant ID Type Subtype PubMed ID
nsv891180 CNV Loss 21882294
nsv891181 CNV Loss 21882294
nsv891182 CNV Gain 21882294

Variation tolerance for RIPK2 Gene

Residual Variation Intolerance Score: 44.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.09; 69.02% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for RIPK2 Gene

HapMap Linkage Disequilibrium report
RIPK2
Human Gene Mutation Database (HGMD)
RIPK2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RIPK2 Gene

Disorders for RIPK2 Gene

Relevant External Links for RIPK2

Genetic Association Database (GAD)
RIPK2
Human Genome Epidemiology (HuGE) Navigator
RIPK2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
RIPK2

No disorders were found for RIPK2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for RIPK2 Gene

Publications for RIPK2 Gene

  1. RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. (PMID: 9575181) Inohara N. … Nunez G. (J. Biol. Chem. 1998) 2 3 4 23 67
  2. Identification of CARDIAK, a RIP-like kinase that associates with caspase-1. (PMID: 9705938) Thome M. … Tschopp J. (Curr. Biol. 1998) 2 3 23
  3. Induction of RIP-2 kinase by proinflammatory cytokines is mediated via NF-kappaB signaling pathways and involves a novel feed-forward regulatory mechanism. (PMID: 19693652) Yin X. … Csizmadia V. (Mol. Cell. Biochem. 2010) 3 23
  4. MS80, a novel sulfated polysaccharide, inhibits CD40-NF-kappaB pathway via targeting RIP2. (PMID: 19911254) Du X. … Jiang H. (Mol. Cell. Biochem. 2010) 3 23
  5. RIP2: a novel player in the regulation of keratinocyte proliferation and cutaneous wound repair? (PMID: 20025869) Adams S. … Munz B. (Exp. Cell Res. 2010) 3 23

Products for RIPK2 Gene

Sources for RIPK2 Gene

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