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FLASH GENE
Symbol RIPK2 contributors: mct/npt/pgu - updated : 10-04-2013
HGNC name receptor-interacting serine-threonine kinase 2
HGNC id 10020
Location 8q21.3      Physical location : 90.769.974 - 90.803.291
Synonym name
  • RIP-like interacting CLARP kinase (CASP8 related)
  • card-containing ice-associated kinase
  • (ICE)-associated kinase
  • CARD-containing interleukin-1 beta-converting
  • enzyme-associated kinase
  • growth-inhibiting gene 30
  • Synonym symbol(s) CARDIAK, RICK, RIP2, CARD3, GIG30, CCK
    EC.number 2.7.11.1/2.7.10.2
    DNA
    TYPE functioning gene
    STRUCTURE 33.32 kb     11 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D8S273 - NBS1 - RIPK2 ,CALB1 - D8S270 - qter
    Authors GeneMap (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 polyA site 2588 60.3 540 - 2009 19667203
    - - - - - - 2009 19667203
  • also called RIP2beta
  • comprised of only a portion of the N-terminal kinase domain and lacking the intermediate region and C-terminal CARD
  • associated with a loss of activation with respect to NF-kappaB and MAPK activation, IL-1beta secretion, and caspase-8-mediated apoptosis
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
    Lymphoid/Immunelymph node    
    Nervousbrain    
    Reproductivemale systemprostate   
     male systemtestis   
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a serine/threonine catalytic kinase domain in the N terminal region
  • a C terminal caspase recruitment domain (CARD)
  • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    text localizes at the plasma membrane in the THP1 cell line and NOD2 is potentially responsible for the membrane recruitment of RIPK2 to induce a regulated NF-kappaB signaling and production of proinflammatory cytokines
    basic FUNCTION
  • regulator of TNFRSF6 (CD95/FAS)-mediated apoptosis
  • transducing signals from receptors of both innate and adaptative unity
  • required for optimal TCR signaling and NF-kappaB activation
  • crucial modulator of epidermal differentiation, and important and unique functions in keratinocytes of normal and wounded skin
  • its polyubiquitination links MAP3K7 to IKK complexes, a critical step in NOD1/NOD2-mediated NF-kappaB activation
  • promotes NF-kappaB activation as well as activation of the MAPKs JNK, ERK1/2 and MAPK14, thereby playing an emergent role in the innate immune response and NOD signaling
  • contributor to NOD signaling, which interacts with NOD1 and NOD2 via CARD-CARD interactions
  • important player in the regulation of keratinocyte proliferation
  • importance of RIPK2 for NOD-dependent induction of innate and adaptive immunity
  • serine/threonine kinase that is involved in multiple nuclear factor-KappaB (NFKB1) activation pathways, including Toll-like receptors
  • is potentially a key regulator of cellular lipid metabolism and cardiovascular disease
  • its tyrosine kinase activity is not only required for NOD2-dependent autophagy but plays a dual role in this process
  • might play an important role in hepatic cell migration
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interading with CARD4, CARD15
  • with CASP1(stress-inducible upstream modulator of procaspase 1 apoptotic activation)
  • interacting with BCL10 and inducing its phosphorylation
  • determines its stability and consequently NOD1- and NOD2-mediated immune responses
  • interacts with XIAP via its BIR2 domain, which could be disrupted by XIAP antagonists SMAC and SMAC-mimicking compounds
  • interaction with XIAP (playing a role in regulating innate immune responses by interacting with NOD1 and NOD2)
  • target of activated receptors of the tumor necrosis factor receptor (TNFR) type, in myogenic differentiation and regeneration
  • XIAP ubiquitylates RIPK2 and recruits the linear ubiquitin chain assembly complex (LUBAC) to NOD2
  • NOD2 stimulates autophagy in a process dependent on RIPK2 tyrosine kinase activity
  • INPP5D C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIPK2 in order to decrease NFKB1 signaling
  • NOD1 CARD binds ubiquitin (Ub), in addition to directly binding its downstream targets receptor-interacting protein kinase 2 (RIPK2) and autophagy-related protein 16-1 (ATG16L1)
  • interaction between TRAF3 and RIPK2 (TRAF3 could inhibit RIPK2-induced NFKB1 activation)
  • RIPK2 is a substrate for PELI3 and PELI3 is an important mediator in the NOD2 pathway and regulator of intestinal inflammation
  • cell & other
    REGULATION
    Other recruited to TLR2 signaling after ligand stimulation
    directly polyubiquitinated by ITCH
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • murine RiP2-/- exhibit a profound decreased ability to defend against infection by the intracellular pathogene Listeria monocytogenes
  • lipid accumulation and inflammation are dissociated in the vessel wall in mice with Ripk2(-/-) macrophages