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FLASH GENE
Symbol RIPK4 contributors: mct - updated : 03-10-2023
HGNC name receptor-interacting serine-threonine kinase 4
HGNC id 496
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 3890 - 784 - 2000 10948194
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Reproductivefemale systembreastmammary gland  
Respiratoryrespiratory tractlarynx   
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier liningepidermis   Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal, twelve subdomains conserved in all protein kinases, serine/threonine kinase domain
  • catalytic kinase domain
  • a potential nuclear localization signal (NLS)
  • a kinase domain as well as unique accessory domains that likely dictate subcellular localization and substrate preferences
  • C-terminal putative regulatory domain containing eleven ankyrin repeats
  • HOMOLOGY
    interspecies ortholog to murine Ripk4
    intraspecies homolog to DAP
    Homologene
    FAMILY
  • serine/threonine family of protein kinase
  • receptor-interacting protein (RIP) kinase family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • protein serine/threonine kinase activity
  • may function in both a kinase-dependent as well as a kinase-independent manner to activate NFkappaB
  • crucial modulator of epidermal differentiation, and important and unique functions in keratinocytes of normal and wounded skin
  • potentially functioning in the epidermis through PKC-specific signaling pathways to regulate differentiation and inflammation
  • important regulator of epidermal morphogenesis during embryonic development
  • RIPK4 requires IKBKB for the induction of the canonical NFKB pathway
  • RIPK4 and CHUK might function via closely related pathways to promote keratinocyte differentiation and epithelial growth
  • with RIPK4, ZBTB21 has potential role in the pathogenesis of Congenital heart defect (CHD) in Down syndrome (DS)
  • RIPK4 and IRF6 function as a cell-intrinsic signaling axis to regulate keratinocyte differentiation
  • is a key regulator of keratinocyte differentiation
  • potential role for RIPK4 in the regulation of keratinocyte cornification
  • key regulator of keratinocyte differentiation, cutaneous inflammation, and cutaneous wound repair
  • RIPK4 can play a dual role as both a tumor promoter and a tumor suppressor in different tumor types
  • RIPK4 is associated with tumor metastasis and implicated in the regulation of the WNT signaling pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • likely RIPK4-IRF6 signaling axis plays a multifaceted role in barrier epithelial homeostasis through its regulation of both keratinocyte inflammation and differentiation
  • a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
    ATP binding
    protein
  • PRKCD
  • interacts with protein kinase C (PKC) isoforms and is implicated in PKC-dependent signaling pathways
  • interacting with BIRC2 (Lys51 and Lys145 of RIPK4 are two critical AAs for BIRC2-mediated ubiquitination and NFKB activation)
  • direct transcriptional target of the protein TP63, a master regulator of stratified epithelial development, which acts as a nodal point in the cascade of molecular events that prevent pterygium syndromes
  • RIPK4 promotes keratinocyte differentiation in part by phosphorylating and thereby activating the IRF6 transcription factor
  • regulatory relationship between RIPK4 and ELF3, an ETS family transcription factor
  • RIPK4 promotes keratinocyte differentiation, in part, by inducing IRF6 transactivator function through the phosphorylation of its C-terminal domain at Ser413 and Ser424
  • cell & other
    REGULATION
    Other its expression is regulated in a complex manner, which might have therapeutic implications
    ASSOCIATED DISORDERS
    corresponding disease(s) PPS2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in cutaneous wound repair, which might be initiated by a broad variety of growth factors and cytokines
    tumoral     --over  
    in ovarian cancer with poor prognosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • can act as a potential prognostic molecular marker for poor survival in Ovarian carcinoma
  • Therapy target
    ANIMAL & CELL MODELS
    Ripk4-null mice exhibiting severe epidermal adhesions that phenocopy Bartsocas-Papas syndrome