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FLASH GENE
Symbol S100A8 contributors: mct - updated : 23-02-2015
HGNC name S100 calcium binding protein A8 (calgranulin A)
HGNC id 10498
Location 1q21.3      Physical location : 153.362.508 - 153.363.549
Genatlas name calprotectin
Synonym name
  • cystic fibrosis associated antigen
  • S100 calcium binding protein A8 (calgranulin A)
  • calprotectin L1L subunit
  • leukocyte L1 complex light chain
  • migration inhibitory factor-related protein 8
  • urinary stone protein band A
  • calgranulin A
  • Synonym symbol(s) CAGA, CFAG, MRP8, MIF, NIF, P8, S108, 60B8AG, CGLA, CP-10, L1Ag, MA387
    DNA
    TYPE breakpoint
    SPECIAL FEATURE component of a cluster
    STRUCTURE 1.16 kb     2 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    SPRL2A 1q21.3 small proline rich-like (epidermal differentiation complex) 2A LEP1 1q21.3 late envelope protein 1 MCSP 1q21 mitochondrial capsule selenoprotein IVL 1q21 involucrin SPRR4 1q21.3 small proline rich protein 4 SPRR1A 1q21 small proline-rich protein 1A SPRR3 1q21 small proline-rich protein 3 SPRR1B 1q21 small proline-rich protein 1B (cornifin) SPRR2A 1q21 small proline-rich protein 2A SPRR2B 1q21 small proline-rich protein 2B SPRR2C 1q21 small proline-rich protein 2C LOC149018 1q22 hypothetical LOC149018 LOC391102 1 similar to 60S acidic ribosomal protein P0 (L10E) LOR 1q21 loricrin PGLYRPIalpha 1q21 peptidoglycan recognition protein-I-alpha precursor PGLYRPIbeta 1q21 peptidoglycan recognition protein-I-beta precursor S100A9 1q21 S100 calcium binding protein A9 (calgranulin B) S100A12 1q21 S100 calcium binding protein A12 (calgranulin C) LOC391103 1 similar to lysosomal-associated transmembrane protein 4 beta; putative integral membrane transporter S100A8 1q21 S100 calcium binding protein A8 (calgranulin A) S100A15 1q22 S100 calcium binding protein A15 S100A7L2 1q22 S100 calcium binding protein A7-like 2 S100A7 1q21 S100 calcium binding protein A7 (psoriasin 1) S100A6 1q21 S100 calcium binding protein A6 (calcyclin) S100A5 1q21 S100 calcium binding protein A5 S100A4 1q21 S100 calcium binding protein A4 (calcium protein, calvasculin, metastasin, murine placental homolog) LOC388700 1 hypothetical gene supported by BT006955; NM_002960 S100A2 1q21 S100 calcium binding protein A2 S100A1 1q21 S100 calcium binding protein A1 DKFZP547E1010 1q22 DKFZP547E1010 protein SNAPAP 1q22 SNAP-associated protein ILF2 1q21.1 interleukin enhancer binding factor 2, 45kDa NPR1 1q21.1 natriuretic peptide receptor A/guanylate cyclase A (atrionatriuretic peptide receptor A) FLJ21919 1q22 hypothetical protein FLJ21919 SLC27A3 1q21.1 solute carrier family 27 (fatty acid transporter), member 3 LOC343052 1q22 similar to putative neuronal cell adhesion molecule P66beta 1q22 transcription repressor p66 beta component of the MeCP1 complex
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 538 11 93 - 2002 12084065
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Cardiovascularheart   highly
    Respiratorylung   highly
    Skin/Tegumentskin     Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Epithelialbarrier liningepidermis   Homo sapiens
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte Homo sapiens
    Blood/Hematopoieticneutrophil Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    Skin/Tegumentkeratinocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two calcium binding domains with an EF-hand motif
  • one S100 specific N terminus
  • one classical C terminus
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine S100a8
    Homologene
    FAMILY
  • S100A8 protein family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton
    basic FUNCTION
  • involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation (epidermal differentiation)
  • involved in the development of epithelial skin tumors
  • playing a role in the inflammatory response to lipopolysaccharide by inducing the release of neutrophils from the bone marrow and directing their migration to the inflammatory site
  • playing a pivotal role during sepsis
  • S100A8/S100A9 levels are likely to be maintained in conditions where IL10 is raised, and these proteins may contribute to viral persistence in patients infected by some RNA viruses
  • bacterial flagellin induces the upregulation of S100A8/S100A9 via a TLR5-dependent mechanism in epidermal keratinocytes (PMID/
  • cytokine-induced potentiated S100A8 and S100A9 expression under conditions, is able to aggravate proinflammatory conditions via activation of the AGER pathway
  • is a potent chemoattractant and also an anti-oxidant, and both roles may be important in the developing placenta
  • pivotal roles of S100A8 and S100A9 in the propagation of inflammation and keratinocyte proliferation in psoriasis
  • S100A8 and S100A9 themselves function as pro-angiogenic and chemotactic factors, generating a psoriatic milieu in skin
  • S100A8 and/or S100A9 promote endothelial cell proliferation, survival, and angiogenesis both directly and by inducing keratinocytes to produce pro-angiogenic cytokines
  • S100A8 and S100A9 are Ca(2+)-binding proteins that are associated with acute and chronic inflammation and cancer
  • S100A8/A9 (calprotectin) negatively regulates G2/M cell cycle progression and growth of squamous cell carcinoma
  • role for S100A8 and S100A9 in redox-sensitive biological responses, including pro-inflammatory cytokine secretion
  • S100A8/A9 (calprotectin) and S100A12 proinflammatory mediators are found at inflammatory sites and in the serum of patients with inflammatory or autoimmune diseases
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • constituent of epidermal differentiation complex
  • heterodimerizing with S100A9 for NADPH oxidase activation in neutrophils
  • S100A8/S100A9-heterodimers are formed in the absence of calcium, tetramerization is strictly calcium-dependent
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • interacting with S100A9 (S100A8-S100A9 complexes amplify the endotoxin-triggered inflammatory responses of phagocytes)
  • interacts with the TLR4-MD2 complex, thus representing an endogenous ligand of TLR4
  • S100A8 and S100A9 interact non-covalently, and that they function coordinately and/or independently as homodimers or heterodimers, depending on the microenvironment
  • functional partner for NADPH oxidase activation contrary to S100A9, however, the loading with calcium and a combination with phosphorylated S100A9 are essential
  • S100A12, S100A8, S100A9 has no direct effect on cholesterol efflux in macrophages, but rather promotes the secretion of IL22, which then directly reduces cholesterol efflux in macrophages by decreasing the expression of ABCG1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in psoriasis and in epithelial skin tumors
    constitutional     --over  
    in numerous inflammatory diseases, such as sepsis, rheumatoid arthritis, inflammatory bowel disease, vasculitis and cancer
    constitutional     --low  
    in placentas of preeclampsia and HELLP syndrome (Buimer 2008)
    tumoral     --over  
    elevated levels of S100A8 or A9 in the ductal fluid, a near absence of pancreatic enzymes, and high levels of mucins were found to have significantly worse prognosis in pancreatic cancer
    constitutional     --over  
    overexpression of S100A8-S100A9 in neurons is an early step in oncogenic KRAS-induced gliosis
    Susceptibility to rheumatoid arthritis
    Variant & Polymorphism
    Candidate gene for lipodystrophy and diabetes
    Marker
  • S100A8 and S100A9 may serve as biomarkers for the detection of renal cell carcinoma
  • potential marker of disease activity in patients with psoriatic arthritis
  • Therapy target
    SystemTypeDisorderPubmed
    dermatologyskin 
    inhibiting S100A8 and/or S100A9 may be a novel therapy targeting various molecular events involved in the initiation of psoriasis
    cancerurinary 
    attractive anticancer target for therapeutic intervention in kidney cancer
    ANIMAL & CELL MODELS
  • S100a8 (-/-) condition is embryonic lethal