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Symbol RIPK3 contributors: mct/npt/pgu - updated : 23-12-2016
HGNC name receptor-interacting serine-threonine kinase 3
HGNC id 10021
TYPE functioning gene
STRUCTURE 4.02 kb     10 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site
MAPPING cloned Y linked N status provisional
Physical map
LOC90668 14q11.2 hypothetical protein BC008134 CPNE6 14q11.2 copine VI (neuronal) NRL 14q11.1-q11.2 neural retina leucine zipper PCK2 14q11.2-q12 phosphoenolpyruvate carboxykinase 2 (mitochondrial) WDR23 14q11.2 WD repeat domain 23 LOC161247 14q11.2 similar to 1110028A07Rik protein PSME1 14q11.2 proteasome (prosome, macropain) activator subunit 1 (PA28 alpha) C14orf122 14q11.2 chromosome 14 open reading frame 122 PSME2 14q11.2 proteasome (prosome, macropain) activator subunit 2 (PA28 beta) RNF31 14q11.2 ring finger protein 31 ISGF3G 14q11.2 interferon-stimulated transcription factor 3, gamma 48kDa REC8L1 14q11.2-q12 REC8-like 1 (yeast) IPO4 14q11.2 importin 4 TM9SF1 14q11.2 transmembrane 9 superfamily member 1 C14orf20 14q11.2 chromosome 14 open reading frame 20 C14orf123 14q11.2 chromosome 14 open reading frame 123 MGC5987 14q11.2 hypothetical protein MGC5987 NEDD8 14q11.2 neural precursor cell expressed, developmentally down-regulated 8 GMPR2 14q11.2 guanosine monophosphate reductase 2 TINF2 14q11.2 TERF1 (TRF1)-interacting nuclear factor 2 TGM1 14q11.2 transglutaminase 1 (K polypeptide epidermal type I, protein-glutamine-gamma-glutamyltransferase) RABGGTA 14q11.2 Rab geranylgeranyltransferase, alpha subunit DHRS1 14q11.2 dehydrogenase/reductase (SDR family) member 1 C14orf21 14q11.2 chromosome 14 open reading frame 21 CIDEB 14q11.2 cell death-inducing DFFA-like effector b LTB4R2 14q11.2-q12 leukotriene B4 receptor 2 LTB4R 14q11.2-q12 leukotriene B4 receptor ADCY4 14q11.2 adenylate cyclase 4 RIPK3 14q11.2 receptor-interacting serine-threonine kinase 3 NFATC4 14q11.2 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 KIAA1305 14q11.2 KIAA1305 HCDI
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
10 - 1940 - 518 - 2009 19524512
   expressed in (based on citations)
cell lineage
cell lines
  • an N-terminal kinase domain similar to that found in RIPK1, RIPK2, and RIPK4 , followed by an RHIM domain, through which it interacts with RIPK1 , and a Ser/Thr kinase domains (KDs)
  • a unique homotypic interaction motif at the C terminus of both RIPK1 and RIPK3 that is required for their association
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • crucial modulator of epidermal differentiation, and important and unique functions in keratinocytes of normal and wounded skin
  • crucial activator for programmed necrosis induced by TNF and during virus infection
  • regulates necrosis-specific RIPK1 phosphorylation
  • controls programmed necrosis by initiating the pronecrotic kinase cascade, and this is necessary for the inflammatory response against virus infections
  • By activating key enzymes of metabolic pathways, RIP3 regulates TNF-induced reactive oxygen species production, which partially accounts for RIP3 ability to promote necrosis
  • RIPK1 and RIPK3 are key signaling molecules in necrosis and are regulated by caspases and ubiquitination
  • key signaling molecule in the programmed necrosis (necroptosis) pathway
  • RIPK1, RIPK3 are central players in TNF-induced programmed necrosis
  • participates in caspase-8 activation by acting downstream of the cytosolic death complex assembly, possibly via reactive oxygen species generation
  • critical regulator of programmed necrosis/necroptosis, an inflammatory form of cell death with important functions in pathogen-induced and sterile inflammation
  • necroptosis is controlled by the action of two serine/threonine kinases, RIPK1 and RIPK3
  • is an essential upstream kinase in necroptosis
  • RIPK1 and RIPK3 directly regulate inflammatory signaling, which complicates interpretation of their function but might alter their therapeutic utility
    a component
  • pronecrotic RIPK1-RIPK3 complex is induced during vaccinia virus infection
  • 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
  • RIPK1 and RIPK3 play a critical role in mediating progressive axonal degeneration
    small molecule
  • binds RIPK1 through its unique C-terminal segment to inhibit RIP- and TNF receptor-1-mediated NF-kappaB activation
  • ZBP1 recruits RIPK1 and RIPK3 through RIP homotypic interaction motifs to activate NF-kappaB
  • BIRC2, BIRC3 are direct E3 ubiquitin ligases for all four RIP proteins and that BIRC2 is capable of conjugating the RIPs with diverse types of ubiquitin chains, including linear chains
  • 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
  • CASP8 control of death receptor and TLR necrotic death signaling depends on basal catalytic activity that suppresses the RIPK3 kinase pathway
  • pseudokinase MLKL functions as a substrate of RIPK3 to mediate downstream signaling
  • MLKL is a key RIPK3 downstream component of tumour necrosis factor (TNF)-induced necroptosis
  • RIPK1 blocks early postnatal lethality mediated by CASP8 and RIPK3
  • XIAP controls RIPK3-dependent cell death and IL1B secretion in response to TNF, which might contribute to hyperinflammation in patients with XLP2
  • RIPK1 intrinsically suppresses spontaneous RIPK3 activation in the cytosol by controlling RIPK3 oligomerization
  • RIPK1 regulates hematopoiesis and prevents inflammation by suppressing RIPK3 activation
  • RIPK3 is an unexpected positive regulator of CASP8 activity that promotes IL1B maturation in bone marrow-derived dendritic cells (BMDCs)
  • HSP90AA1 and CDC37 cochaperone complex-mediated protein folding is thus an important part of the RIPK3 activation process during necroptosis.
  • PGAM5 is a mitochondrial phosphatase that has been reported to function downstream of RIPK3 to promote necroptosis and IL1B secretion
  • RHIM motif of RIPK1 is critical for preventing ZBP1/RIPK3/MLKL-dependent necroptosis during development
  • RIPK3 interacts with MAVS to regulate type I IFN-mediated immunity to Influenza A virus infection
  • cell & other
    Other FADD prevents RIPK3-mediated epithelial cell necrosis and chronic intestinal inflammation
    corresponding disease(s)
    Variant & Polymorphism
    Candidate gene potential drug target for necrosis-related diseases (PMID :
    Therapy target
    RIPK3(-/-) mice exhibited severely impaired virus-induced tissue necrosis, inflammation, and control of viral replication