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RIPK2 Gene

protein-coding   GIFtS: 73
GCID: GC08P090769

Receptor-Interacting Serine-Threonine Kinase 2

  Search for RIPK2
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Receptor-Interacting Serine-Threonine Kinase 21 2     GIG302
Receptor-Interacting Protein 22 3     CARD-Carrying Kinase2
Tyrosine-Protein Kinase RIPK22 3     CARD-Containing Interleukin-1 Beta-Converting Enzyme (ICE)-Associated
Kinase2
CARDIAK2 3     Growth-Inhibiting Gene 302
RICK2 3     Receptor-Interacting Protein (RIP)-Like Interacting Caspase-Like Apoptosis
Regulatory Protein (CLARP) Kinase2
RIP-22 3     Receptor-Interacting Serine/Threonine-Protein Kinase 22
RIP22 3     EC 2.7.10.23
CARD-Containing IL-1 Beta ICE-Kinase2 3     CARD-Containing Interleukin-1 Beta-Converting Enzyme-Associated Kinase3
EC 2.7.11.13 8     RIP-Like-Interacting CLARP Kinase3
CARD32     EC 2.7.118
CCK2     

External Ids:    HGNC: 100201   Entrez Gene: 87672   Ensembl: ENSG000001043127   OMIM: 6034555   UniProtKB: O433533   

Export aliases for RIPK2 gene to outside databases

Previous GC identifers: GC08P089201 GC08P090502 GC08P090726 GC08P090839 GC08P085980


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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. GO annotations related to this gene include protein homodimerization activity and signal transducer activity. An important paralog of this gene is RIPK3.

UniProtKB/Swiss-Prot: RIPK2_HUMAN, O43353
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

summary for RIPK2 Gene:
Cholecystokinin (CCK) is a neuropeptide and gut hormone that regulates pancreatic enzyme secretion and
gastrointestinal motility, and acts as a satiety signal. It is released simultaneously from intestinal cells
and neurons in response to a meal. The precursor molecule prepro-CCK can be cleaved to generate a variety of
biologically active forms of CCK including CCK-33, CCK-8 (CCK octapeptide), CCK-39 and CCK-58. Two CCK
receptor subtypes, CCK1 and CCK2, mediate the physiological actions of CCK and the related peptide gastrin.
The CCK1 receptor has a high affinity for sulfated CCK analogs, whereas the CCK2 receptor has similar
affinity for sulfated and non-sulfated forms.

Gene Wiki entry for RIPK2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000008.10  NT_008046.17  NC_018919.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the RIPK2 gene promoter:
         AML1a   AP-1   ATF-2   LCR-F1   NF-kappaB   RORalpha2   FOXL1   c-Jun   Msx-1   NF-kappaB1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidRIPK2 promoter sequence
   Search Chromatin IP Primers for RIPK2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat RIPK2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 8q21   Ensembl cytogenetic band:  8q21.3   HGNC cytogenetic band: 8q21

RIPK2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RIPK2 gene location

GeneLoc information about chromosome 8         GeneLoc Exon Structure

GeneLoc location for GC08P090769:  view genomic region     (about GC identifiers)

Start:
90,769,975 bp from pter      End:
90,803,292 bp from pter
Size:
33,318 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: RIPK2_HUMAN, O43353 (See protein sequence)
Recommended Name: Receptor-interacting serine/threonine-protein kinase 2  
Size: 540 amino acids; 61195 Da
Subunit: 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
1 PDB 3D structure from and Proteopedia for RIPK2:
4C8B (3D)    
Secondary accessions: B7Z748 Q6UWF0
Alternative splicing: 2 isoforms:  O43353-1   O43353-2   

Explore the universe of human proteins at neXtProt for RIPK2: NX_O43353

Explore proteomics data for RIPK2 at MOPED

Post-translational modifications: 

  • 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 activation1
  • 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-B1
  • Ubiquitination2 at Lys209
  • Modification sites at PhosphoSitePlus
  • 2 DME Specific Peptides for RIPK2 (O43353)
     YMPNGSL  WEVLSRKQPF 


    See RIPK2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_003812.1  
    ENSEMBL proteins: 
     ENSP00000220751   ENSP00000429271   ENSP00000427736   ENSP00000441623  
    Reactome Protein details: O43353

    RIPK2 Human Recombinant Protein Products:

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    Novus Biologicals RIPK2 Proteins
    Novus Biologicals RIPK2 Lysates
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    Browse Sino Biological Cell Lysates
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    Cloud-Clone Corp. Proteins for RIPK2

     
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    RIPK2 Antibody Products:

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    RIPK2 Assay Products:

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    Search eBioscience for ELISAs for RIPK2 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: receptor-interacting serine-threonine kinase 2
    Receptor interacting protein kinase (RIPK) family

    Selected InterPro protein domains (see all 6):
     IPR011029 DEATH-like_dom
     IPR011009 Kinase-like_dom
     IPR008271 Ser/Thr_kinase_AS
     IPR000719 Prot_kinase_dom
     IPR017322 Rcpt-int_Ser/Thr_kinase-2

    Graphical View of Domain Structure for InterPro Entry O43353

    ProtoNet protein and cluster: O43353

    UniProtKB/Swiss-Prot: RIPK2_HUMAN, O43353
    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
    Similarity: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family
    Similarity: Contains 1 CARD domain
    Similarity: Contains 1 protein kinase domain


    Find genes that share domains with RIPK2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: RIPK2_HUMAN, O43353
    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
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate

         Genatlas biochemistry entry for RIPK2:
    receptor interacting serine-threonine kinase 2,widely expressed with two transcripts due to differential
    polyadenylation,regulator of TNFRSF6 (CD95)-mediated

         Enzyme Numbers (IUBMB): EC 2.7.11.11 2 EC 2.7.112 EC 2.7.10.21

         Gene Ontology (GO): Selected molecular function terms (see all 11):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004674protein serine/threonine kinase activity IEA--
    GO:0004713protein tyrosine kinase activity ----
    GO:0004715non-membrane spanning protein tyrosine kinase activity IEA--
    GO:0004871signal transducer activity TAS9642260
         
    Find genes that share ontologies with RIPK2           About GenesLikeMe


    Phenotypes:
         4 GenomeRNAi human phenotypes for RIPK2:
     Decreased substrate adherent c  Gemcitabine induced cell-death  Increased cell death HMECs cel  Upregulation of Wnt/beta-caten 

         3 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Ripk2):
     digestive/alimentary  hematopoietic system  immune system 

    Find genes that share phenotypes with RIPK2           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for RIPK2: Ripk2tm1Flv Ripk2tm1Cfl Ripk2tm1Ghc

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for RIPK2
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for RIPK2

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for RIPK2
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for RIPK2

    miRNA
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    miRTarBase miRNAs that target RIPK2:
    hsa-mir-1 (MIRT024084), hsa-mir-98-5p (MIRT027839)

    Block miRNA regulation of human, mouse, rat RIPK2 using miScript Target Protectors
    5 qRT-PCR Assays for microRNAs that regulate RIPK2:
    hsa-miR-135b hsa-miR-200c hsa-miR-429 hsa-miR-200b hsa-miR-135a
    SwitchGear 3'UTR luciferase reporter plasmidRIPK2 3' UTR sequence
    Inhib. RNA
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    Sino Biological Human cDNA Clone for RIPK2
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    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat RIPK2
    Addgene plasmids for RIPK2 

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for RIPK2


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    RIPK2_HUMAN, O43353: Cytoplasm (Probable)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    nucleus2

    Gene Ontology (GO): Selected cellular component terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005622intracellular ----
    GO:0005737cytoplasm IDA--
    GO:0005829cytosol TAS--
    GO:0005856cytoskeleton IDA--
    GO:0031982vesicle IDA--

    Find genes that share ontologies with RIPK2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for RIPK2 About   (see all 28)  
    See pathways by source

    SuperPathContained pathways About
    1Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
    Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways0.68
    NOD-like receptor signaling pathway0.37
    NOD1/2 Signaling Pathway0.68
    NOD pathway0.33
    2Toll Like Receptor 7/8 (TLR7/8) Cascade
    Toll Like Receptor 9 (TLR9) Cascade0.93
    MyD88 dependent cascade initiated on endosome0.69
    TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation0.93
    MyD88-independent cascade0.69
    Toll Like Receptor 7/8 (TLR7/8) Cascade0.69
    Toll Like Receptor 3 (TLR3) Cascade0.69
    3p75 NTR receptor-mediated signalling
    p75 NTR receptor-mediated signalling0.74
    p75NTR signals via NF-kB0.00
    p75NTR recruits signalling complexes0.00
    4MAPK targets/ Nuclear events mediated by MAP kinases
    MAP kinase activation in TLR cascade0.61
    JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK10.00
    activated TAK1 mediates p38 MAPK activation0.00
    5TCR signaling (REACTOME)
    Downstream TCR signaling0.73
    TCR signaling0.73


    Find genes that share SuperPaths with RIPK2           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for RIPK2
        NOD-like Receptor Signaling Pathways

    3 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for RIPK2
        Caspase Cascade
    Toll-Like Receptors Pathway
    Fas Signaling

    2 Cell Signaling Technology (CST) Pathways for RIPK2
        Apoptosis and Autophagy
    NF-kappaB Signaling

    1 GeneGo (Thomson Reuters) Pathway for RIPK2
        Transcription NF-kB signaling pathway

    Selected BioSystems Pathways for RIPK2 (see all 7)
        NOD pathway
    FAS pathway and Stress induction of HSP regulation
    TNF-alpha/NF-kB Signaling Pathway
    TCR Signaling Pathway
    p75(NTR)-mediated signaling


    Selected Reactome Pathways for RIPK2 (see all 7)
        Interleukin-1 signaling
    p75NTR recruits signalling complexes
    activated TAK1 mediates p38 MAPK activation
    JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
    Downstream TCR signaling


    4 Kegg Pathways  (Kegg details for RIPK2):
        NOD-like receptor signaling pathway
    Neurotrophin signaling pathway
    Shigellosis
    Tuberculosis

        Pathway & Disease-focused RT2 Profiler PCR Arrays including RIPK2 (see all 10): 
              Toll-Like Receptor Signaling Pathway in human mouse rat
              Inflammasomes in human mouse rat
              Inflammatory Response & Autoimmunity in human mouse rat
              Apoptosis in human mouse rat
              T-cell & B-cell Activation in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for RIPK2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for RIPK2 (O433531, 2, 3 ENSP000002207514) via UniProtKB, MINT, STRING, and/or I2D (see all 134)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000183311P074372, 3MINT-49068 I2D: score=2 
    ENSG00000224156P074372, 3MINT-49068 I2D: score=2 
    ENSG00000227739P074372, 3MINT-49068 I2D: score=2 
    ENSG00000229684P074372, 3MINT-49068 I2D: score=2 
    ENSG00000232421P074372, 3MINT-49068 I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 65):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000187activation of MAPK activity TAS--
    GO:0001961positive regulation of cytokine-mediated signaling pathway IEA--
    GO:0002224toll-like receptor signaling pathway TAS--
    GO:0002250adaptive immune response ISS--
    GO:0002755MyD88-dependent toll-like receptor signaling pathway TAS--

    Find genes that share ontologies with RIPK2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Compounds for RIPK2 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    CCK Octapeptide, sulfated C-terminal octapeptide of CCK[25126-32-3]
    CCK Octapeptide, non-sulfated Non-sulfated form of CCK octapeptide[25679-24-7]
    Proglumide sodium saltNon-selective CCK antagonist; orally active[99247-33-3]

    2 HMDB Compounds for RIPK2    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    4 Novoseek inferred chemical compound relationships for RIPK2 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    threonine 55.8 12 15724446 (1), 15755681 (1), 16164210 (1), 16465024 (1) (see all 9)
    peptidoglycan 55 3 15289440 (1), 16582588 (1), 15691843 (1)
    serine 43.2 10 15755681 (1), 16164210 (1), 16465024 (1), 18606014 (1) (see all 8)
    sb 203580 40.8 4 15691843 (2), 15289440 (1), 15724446 (1)



    Find genes that share compounds with RIPK2           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for RIPK2 gene: 
    NM_003821.5  

    Unigene Cluster for RIPK2:

    Receptor-interacting serine-threonine kinase 2
    Hs.103755  [show with all ESTs]
    Unigene Representative Sequence: NM_003821
    5 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000220751(uc003yee.3 uc003yef.3) ENST00000522965 ENST00000517696
    ENST00000518673 ENST00000540020
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    Additional mRNA sequence: 

    AF027706.1 AF064824.1 AF078530.1 AK075213.1 AK301448.1 AY358813.1 AY358814.1 AY524045.1 
    BC004553.2 

    3 DOTS entries:

    DT.313934  DT.95279922  DT.121469798 

    Selected AceView cDNA sequences (see all 155):

    CR596906 AA765509 BQ773811 BQ670832 CB851847 BG393551 AA574167 BM469352 
    AI745575 BX280487 BM557041 AY562996 CR592019 AY358814 BQ010938 AA740822 
    BM855477 NM_003821 BG757422 AI475356 BQ008463 AA825196 BF754627 BM840808 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for RIPK2    About this scheme

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


    ECgene alternative splicing isoforms for RIPK2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    RIPK2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TAAGTGACTG
    RIPK2 Expression
    About this image


    RIPK2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Brain (Nervous System)    fully expand to see all 3 entries
             Cerebral Cortex
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
     
     Bone (Muscoskeletal System)
             Bone Marrow
    RIPK2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    RIPK2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.103755

    UniProtKB/Swiss-Prot: RIPK2_HUMAN, O43353
    Tissue specificity: Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis,
    prostate, pancreas and lymph node

        Pathway & Disease-focused RT2 Profiler PCR Arrays including RIPK2 (see all 10): 
              Toll-Like Receptor Signaling Pathway in human mouse rat
              Inflammasomes in human mouse rat
              Inflammatory Response & Autoimmunity in human mouse rat
              Apoptosis in human mouse rat
              T-cell & B-cell Activation in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for RIPK2 gene from Selected species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Ripk21 , 5 receptor (TNFRSF)-interacting serine-threonine kinase more1, 5 85.16(n)1
    84.42(a)1
      4 (6.70 cM)5
    1926561  NM_138952.31  NP_620402.11 
     161227335 
    chicken
    (Gallus gallus)
    Aves RIPK21 receptor-interacting serine-threonine kinase 2 70.42(n)
    69.32(a)
      420215  NM_001030943.1  NP_001026114.1 
    lizard
    (Anolis carolinensis)
    Reptilia RIPK26
    receptor-interacting serine-threonine kinase 2
    62(a)
    1 ↔ 1
    4(21554203-21580215)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia ripk21 receptor-interacting serine-threonine kinase 2 62.02(n)
    59.19(a)
      100496958  XM_002939155.2  XP_002939201.2 
    zebrafish
    (Danio rerio)
    Actinopterygii ripk22 receptor-interacting serine-threonine kinase 2 74.62(n)   373874  AF487540.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for RIPK2 gene
    RIPK32  RIPK42  RIPK12  ANKK12  

    Find genes that share paralogs with RIPK2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for RIPK2 (see all 790)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 8 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1417372461,2
    --90768268(+) GGACAA/GTGAGT 1 -- us2k10--------
    rs69811121,2
    C,F,A--90768362(+) cctacC/Tcaaat 1 -- us2k18Minor allele frequency- T:0.13NA WA CSA 132
    rs4057341,2
    C,F,A,H--90768439(+) cccacG/Atgatt 1 -- us2k114Minor allele frequency- A:0.31NA WA CSA EA 377
    rs1865096081,2
    --90768460(+) TTGCTC/TACCCA 1 -- us2k10--------
    rs1901276741,2
    --90768498(+) GACGCC/GCGTTA 1 -- us2k10--------
    rs4267791,2
    C,F,A,H--90768566(+) CCGGGG/CGCGGT 1 -- us2k17Minor allele frequency- C:0.36NA WA CSA 14
    rs1827087811,2
    --90768599(+) ACTTTA/GGGAGG 1 -- us2k10--------
    rs583306171,2
    C--90768642(+) GAGACC/TAGCTT 1 -- us2k10--------
    rs1869871591,2
    --90768713(+) GGGCGA/CCTGTA 1 -- us2k10--------
    rs562759011,2
    C--90768747(+) GGCAGA/GAGAAT 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for RIPK2 (90769975 - 90803292 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for RIPK2:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv891180CNV Loss21882294
    nsv891181CNV Loss21882294
    nsv891182CNV Gain21882294

    Human Gene Mutation Database (HGMD): RIPK2
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing RIPK2
    DNA2.0 Custom Variant and Variant Library Synthesis for RIPK2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 603455    OMIM disorders: --

    2 diseases from the University of Copenhagen DISEASES database for RIPK2:
    Taylor's syndrome     Crohn's disease

    Find genes that share disorders with RIPK2           About GenesLikeMe

    3 Novoseek inferred disease relationships for RIPK2 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    inflammation 37.3 3 18205922 (1), 16354923 (1), 18702009 (1)
    necrosis 24.2 6 17348859 (1), 10559258 (1), 10880512 (1), 11551959 (1) (see all 5)
    tumors 0 4 10559258 (1), 10880512 (1), 11551959 (1), 10329646 (1)

    Genetic Association Database (GAD): RIPK2
    Human Genome Epidemiology (HuGE) Navigator: RIPK2 (8 documents)

    Export disorders for RIPK2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for RIPK2 gene, integrated from 10 sources (see all 157):
    (articles sorted by number of sources associating them with RIPK2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. RICK, a novel protein kinase containing a caspase recruitment domain, interacts with CLARP and regulates CD95-mediated apoptosis. (PubMed id 9575181)1, 2, 3, 9 Inohara N.... Nunez G. (J. Biol. Chem. 1998)
    2. Identification of CARDIAK, a RIP-like kinase that associates with caspase-1. (PubMed id 9705938)1, 2, 3, 9 Thome M.... Tschopp J. (Curr. Biol. 1998)
    3. A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF- kappaB activation. (PubMed id 18079694)1, 2, 9 Hasegawa M....Inohara N. (EMBO J. 2008)
    4. RIP2 is a novel NF-kappaB-activating and cell death-inducing kinase. (PubMed id 9642260)1, 2, 9 McCarthy J.V.... Dixit V.M. (J. Biol. Chem. 1998)
    5. ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways. (PubMed id 19592251)1, 2, 9 Tao M....Abbott D.W. (Curr. Biol. 2009)
    6. Solution structure of NOD1 CARD and mutational analysis of its interaction with the CARD of downstream kinase RICK. (PubMed id 17054981)1, 2, 9 Manon F.... Cusack S. (J. Mol. Biol. 2007)
    7. Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1. (PubMed id 21887730)1, 2 Zhao Y....Reinecker H.C. (Inflamm. Bowel Dis. 2012)
    8. cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4). (PubMed id 21931591)1, 2 Bertrand M.J.... Vandenabeele P. (PLoS ONE 2011)
    9. Common genetic variation and performance on standardized cognitive tests. (PubMed id 20125193)1, 4 Cirulli E.T....Goldstein D.B. (Eur. J. Hum. Genet. 2010)
    10. Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study. (PubMed id 20800603)1, 4 Flachsbart F....Nebel A. (Mutat. Res. 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 8767 HGNC: 10020 AceView: RIPK2 Ensembl:ENSG00000104312 euGenes: HUgn8767
    ECgene: RIPK2 Kegg: 8767 H-InvDB: RIPK2

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for RIPK2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for RIPK2 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for RIPK2 gene:
    Search GeneIP for patents involving RIPK2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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