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FLASH GENE
Symbol RIPK1 contributors: mct/shn - updated : 01-11-2012
HGNC name receptor (TNFRSF)-interacting serine-threonine kinase 1
HGNC id 10019
Location 6p25.2      Physical location : 3.077.057 - 3.115.419
Synonym name
  • receptor interacting protein
  • death domain kinase
  • RIP1 kinase
  • cell death protein RIP
    • Synonym symbol(s) FLJ39204, RIP, RIP1
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 38.42 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D6S1600 - D6S344 - RIPK1 - D6S1617 - D6S1617 - cen
    Physical map
    LOC285770 6p25.2 similar to FLJ00254 protein C6orf195 6p25.2 chromosome 6 open reading frame 195 LOC340156 6p25.2 hypothetical protein LOC340156 WRNIP1 6p24.3 Werner helicase interacting protein 1 SERPINB1 6p25 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 1 SERPINB9 6p25 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 9 SERPINB6 6p25 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 6 NQO2 6p25-p24.3 NAD(P)H dehydrogenase, quinone 2 LOC391864 6 similar to HIV TAT specific factor 1; cofactor required for Tat activation of HIV-1 transcription LOC221754 6p25.2 similar to dJ40E16.3 (novel gene similar to D. melanogaster CG5327 ) RIPK1 6p25.3-p24.1 receptor (TNFRSF)-interacting serine-threonine kinase 1 BPHL 6p25 biphenyl hydrolase-like (serine hydrolase; breast epithelial mucin-associated antigen) TUBB 6p21.3 tubulin, beta polypeptide MGC8685 6p25 tubulin, beta polypeptide paralog LOC389362 6 LOC389362 C6orf85 6p25.2 chromosome 6 open reading frame 85 DKFZP434F011 6p25.2-p25.1 ion transporter protein C6orf145 6p25.1 chromosome 6 open reading frame 145 D6S2654E 6pter DNA segment on chromosome 6(unique) 2654 expressed sequence LOC389363 6 hypothetical gene supported by AF118652; NM_006541 PRPF4B 6p24.2 PRP4 pre-mRNA processing factor 4 homolog B (yeast) C6orf146 6p25.1 chromosome 6 open reading frame 146 PECI 6p24.3 peroxisomal D3,D2-enoyl-CoA isomerase
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3864 - 671 - 2007 17235653
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     intestinesmall intestine   
    Nervousbrain    
    Reproductivemale systemtestis   
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal region with homology to protein kinases, and a Ser/Thr kinase domains (KDs)
  • an intermediate domain of RIPK1 harbors an anti-apoptotic function, with a RHIM domain
  • a C terminal region containing a DEATH domain, and a unique homotypic interaction motif at the C terminus of both RIPK1 and RIPK3 that is required for their association , and also for recruitment to the TNF receptor signaling complex
    • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to Ripk1, Mus musculus
    ortholog to Ripk1, Rattus norvegicus
    ortholog to RIPK1, Pan troglodytes
    Homologene
    FAMILY
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text present both in the cytoplasm and in the nucleus
    basic FUNCTION
  • dual-function molecule that can be either prosurvival or prodeath depending on its ubiquitination state, and this serves as an NF-kappaB-independent cell-death switch early in TNF signaling
  • playing an important role for DNA damage-induced, TP53-independent cell death
  • one of the critical components involved in mediating DNA damage-induced, TP53-independent cell death
  • one of the major components of the tumor necrosis factor receptor 1 complex and plays an essential role in tumor necrosis factor-mediated nuclear factor kappaB activation (
  • plays a critical role in tumor necrosis factor-alpha (TNF)-induced IkappaB kinase (IKK) activation and subsequent activation of transcription factor NF-kappaB
  • inhibiting the expression of the epidermal growth factor receptor (EGFR)
  • crucial modulator of epidermal differentiation, and important and unique functions in keratinocytes of normal and wounded skin
  • specifically recruited to the TNFalpha receptor in the activation of necroptosis
  • critical mediator of inflammation and stress-induced NF-kappaB activation, regulates the expression of the epidermal growth factor receptor (EGFR)
  • downregulates EGFR expression by interfering with the function of Sp1, which is a key activator of EGFR transcription
  • required for death receptor agonists to activate necrosis
  • RIPK1 and RIPK3 are key signaling molecules in necrosis and are regulated by caspases and ubiquitination
  • required for CD40 ligand-induced caspase-8 activation and tumor cell killing
  • RIPK1 and caspase-8 were recruited to the DDX58 complex after viral infection and served antagonistic regulatory roles
  • regulates embryogenesis and lymphocyte responses (
  • a IKBKG- and RIPK1-based switch mechanism involving TNF-TNFR1 feedforward signaling that mediates ATM-induced cytokine secretion and caspase activation selectively in the context of severe DNA damage
  • is a central kinase in TNFR1 signaling participating in NFKB activation, necroptosis, and apoptosis
  • functions as a platform mediating survival signals and as an active kinase during necroptosis and apoptosis in the presence of Smac mimetics
  • RIPK1, RIPK3 are central players in TNF-induced programmed necrosis
  • key switch of cell fate regulation
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    interacting with IKBKG and modulatory NF-kappa B activation and apoptosis
    a component
  • RIPK1 and RIPK3 form an amyloid structure through their RHIMs and that this heterodimeric amyloid structure is a functional signaling complex that mediates programmed necrosis
    • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
    • protein
  • Fas/APO-1 (CD95) (
  • TNFRSF1A-associated via death domain, TRADD (
  • FADD/MORT1 (
  • Death receptor 4, DR4 and Death receptor 5, DR5 (
  • TNFRSF1A
  • aPKC-binding protein, p62 (
  • heat shock protein 90, Hsp90 (
  • NEMO (IKKgamma) (
  • epidermal growth factor receptor, EGFR (
  • IKBKG and modulatory NF6kappa B activation and apoptosis
  • RIPK3
  • zinc finger protein inhibiting NF-kappa B (
  • Focal adhesion kinase, FAK (
  • RNF216 (E3 ubiquitin-protein ligase to RIPK1 and Hsp90 and RNF216 cooperatively maintain the homeostasis of RIPK1
  • cylindromatosis (turban tumor syndrome), CYLD (
  • CSNK1A1
  • TAK1 kinase (
  • ZBP1 recruits RIPK1 and RIPK3 through RIP homotypic interaction motifs to activate NF-kappaB
  • ubiquitin specific peptidase 21, USP21
  • links the immunoregulatory CD40 receptor to apoptotic signaling in carcinomas
  • RIPK1
  • CD40 (
  • interacting with ATM (in the context of excessive DNA damage, ATM employs IKBKG and RIPK1 through autocrine TNF signaling to switch on cytokine production and caspase activation)
  • FCMR regulates the balance between apoptotic and nonapoptotic death receptor signaling by facilitating RIPK1 ubiquitination
  • PGAM5 is a kinase substrate of RIPK1/RIPK3
  • necroptosis depends on the kinases RIPK1 and RIPK3, which interact through their RHIM domains to form the necrosome
  • recruitment of IKBKG to ubiquitinated RIPK1 is a key step in the TNFR1 signaling pathway that determines whether RIPK1 triggers a necrotic death response
    • cell & other
    REGULATION
    Other regulated by TRADD
    negatively regulated by RNF11 (
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in glomerulus and tubule of class III and IV lupus nephritis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • RIP-deficient mice appear normal at birth but fail to thrive, displaying extensive apoptosis in both the lymphoid and adipose tissue and dying at 1-3 days of age (
  • RIP1 deficiency allowed normal embryogenesis of Fadd(-/-) mice and the developmental defect of Rip1(-/-) lymphocytes was partially corrected by FADD deletion (
  • Fadd(-/-)Rip1(-/-) double-knockout T cells are resistant to death induced by Fas or TNF-&
    • 945; and show reduced NF-&
    954;B activity (