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FLASH GENE
Symbol CD14 contributors: shn/mct - updated : 07-04-2020
HGNC name CD14 molecule
HGNC id 1628
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 11 leucine rich repeats
  • a region spanning amino acids 57-64 critical for interacting with TLR2 and enhancing TLR2-mediated peptidoglycan signaling
    • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to Cd14, Mus musculus
    ortholog to Cd14, Rattus norvegicus
    Homologene
    FAMILY
    CATEGORY antigen , receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic,granule
    text attached to the membrane by a GPI-anchor
    basic FUNCTION
  • functional receptor for peptidoglycan
  • receptor for bacterial liposaccharides, recruiting LPS to TLR proteins and inducing a liposaccharide signaling pathway
  • involved in the clearance of apoptotic cells
  • regulator of IgE levels
  • enhancing Toll-like receptor 2 (TLR2)-mediated signaling in response to peptidoglycan
  • plays a major role in the inflammatory response of monocytes to lipopolysaccharide (LPS)
  • critical regulator of the microglial inflammatory response that acts to modulate betta-amyloid deposition
  • CD14 modulates adipose tissue inflammatory activity and insulin resistance 1)
  • is a monocytic differentiation antigen that regulates innate immune responses to pathogens
  • stimulation of a local CD14-independent chemokine induction pathway without triggering a systemic CD14-dependent chemokine pathway can protect against severe E. coli infections
  • plays a very important role in transferring LPS from LPS-binding protein to TLR4, which was regarded as the initiation of TLR4 signaling
  • is a key organizer of microglial responses to CNS infection and injury
  • function of the innate immune response by CD14 is crucial during biliary infection and stricture formation
  • new roles for CD14 and IL1B linking inflammatory dendritic cells to IL17A production in memory CD4+ T cells
  • is a key mediator of both lysophosphatidic acid and lipopolysaccharide induction of foam cell formation
  • cell surface glycoprotein, which plays an important role in the occurrence and development of tumors
  • is a monocyte/macrophage pattern-recognition receptor that modulates innate inflammatory signaling
  • CD14 expression on macrophages is necessary for airway inflammation but not for viral pathogenesis in allergic hosts
  • CD14 might play an important role in self-remission of gout
    • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    text innate immunity
    PATHWAY
    metabolism
    signaling signal transduction
    MAP kinase and NF-kappa B pathway
    a component component of a complex with TLR4 and LY96 binding LPS and trafficking to Golgi apparatus to plasma membrane
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Mac-2-binding protein, Mac-2-BP
  • Toll-like receptor 2, TLR2
  • lactoferrin, LTF
  • ceramide, CD55, Fcgamma-receptors CD32, CD64 and the pentaspan CD47
  • lipopolysaccharide, LPS and lipopolysaccharide binding protein, LBP
  • in gastric cancer CD14 promoted tumor cell epithelial-mesenchymal transition (EMT) and invasion through TNF
  • CD14 mediates binding of high doses of LPS but is dispensable for TNF production
  • CD14 is an endogenous ligand for CD33 and ligation of CD33 with CD14 modulates with the presentation of LPS from CD14 to TLR4, leading to down-regulation of TLR4-mediated signaling
  • CD14 is a co-receptor of TLR4 in the S100A9-induced cytokine response
  • LGALS4 could bind to CD14 on monocytes and induce their differentiation into macrophage-like cells through the MAPK signaling pathway
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in preterm infants with Early-onset sepsis (EOS) compared with uninfected infants
    tumoral     --other  
    dysfunction in the CD14/TLR4 antagonism may contribute to normal epithelial transition to colonic carcinogenesis
    Susceptibility
  • severe chronic periodontitis
  • to Crohn disease (in association with CARD15)
  • to IgA nephropathy in progression
  • to laryngeal cancer
  • to non-alcoholic fatty liver disease (NAFLD)
    • Variant & Polymorphism
  • 159 TT allele and1359G:/T increases this risk of Crohn disease
  • T159C associated to IgA nephropathy in progression
  • genetic variation of CD14, rs5744455, is related to the susceptibility to laryngeal cancer
  • CD14 C (-159) T gene polymorphism, a co-receptor of TLR4, have an increased risk of NAFLD development
    • Candidate gene
    Marker
  • presepsin could be a useful biomarker for the early diagnosis of sepsis, also for pediatric sepsis
  • plasma soluble CD14 level might be a potential biomarker in prediction of asthma severity in adults
  • presepsin could be a useful biomarker of sepsis secondary to fungal infections
  • is a valuable biomarker to detect patients with acute pyelonephritis
    • Therapy target
    ANIMAL & CELL MODELS
  • CD14-deficient miceare highly resistant to shock induced by either live Gram-negative bacteria or LPS and show dramatically reduced levels of bacteremia
  • Bone marrow-derived macrophages (BMDMs) from CD14-/- mice exhibited impaired responses to polyinosine-polycytidylic acid (pIpC) and reduced production of inflammatory cytokines
  • mice lacking CD14 exhibited reduced insoluble, but not soluble, levels of betta-amyloid at 7 months of age and have a significant change in the inflammatory environment of the brain