Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol RIPK3 contributors: mct/npt/pgu - updated : 23-12-2016
HGNC name receptor-interacting serine-threonine kinase 3
HGNC id 10021
Location 14q12      Physical location : 24.805.227 - 24.809.242
Synonym name
  • RIP-like protein kinase 3
  • receptor interacting protein 3
  • Synonym symbol(s) RIP3, RIP-3
    EC.number 2.7.11.1
    DNA
    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
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 1940 - 518 - 2009 19524512
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
  • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • TKL Ser/Thr protein kinase family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic
    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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    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
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
  • unexpected roles for RIPK1 and RIPK3 kinases in the production of IFNB1 during the host inflammatory responses to bacterial infection, suggesting that the axis in which these kinases operate may represent a target for bacterial virulence factors
  • cell & other
    REGULATION
    Other FADD prevents RIPK3-mediated epithelial cell necrosis and chronic intestinal inflammation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene potential drug target for necrosis-related diseases (PMID :
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    RIPK3(-/-) mice exhibited severely impaired virus-induced tissue necrosis, inflammation, and control of viral replication