protein S100-A8; S100 Ca+2-binding protein A8; calgranulin-A; migration inhibitory factor-related protein 8; MRP-8; p8; Cystic fibrosis antigen; CFAG; Leukocyte L1 complex light chain; calprotectin L1L subunit; urinary stone protein band A (S100A8, CAGA, CFAG, MRP8)

Function

• Ca+2-binding protein
• antimicrobial activity towards bacteria & fungi
• important for resistance to invasion by pathogenic bacteria
• up-regulates transcription of genes that are under the control of NF-kappa-B
• promotes tubulin polymerization
• promotes phagocyte migration & infiltration of granulocytes at sites of wounding
• plays a role as pro-inflammatory mediator in acute & chronic inflammation & up-regulates release of IL8 & cell-surface expression of ICAM1
• antimicrobial & proapoptotic activity is inhibited by Zn+2
• homodimer; heterotetramer with S100A9
• component of the heterotetrameric calprotectin complex
• interacts with AGER & with the heterodimeric complex formed by TLR4 & LY96
• interacts with CEACAM3 & tubulin filaments (Ca+2-dependent)
• may interact with components of the intermediate filaments in monocytes & epithelial cells
• binds two Ca+2 per molecule with an affinity similar to that of the S100 proteins

Structure

• belongs to the S-100 family
• contains 2 EF-hand domains

Compartment

• secreted, cytoplasm, cytoskeleton
• cell membrane; peripheral membrane protein
• associates with tubulin filaments in activated monocytes targeted to the cell surface upon Ca+2 influx

Expression

• expressed by macrophages in chronic inflammation
• also expressed in epithelial cells constitutively or induced during dermatoses
• expressed in granulocytes & restricted set of normal stratified squamous epithelia, excluding pancreas, lungs & skin where cystic fibrosis defect is manifested

Pathology

• released from blood leukocytes upon exposure to CSF2/GM-CSF, bacterial lipopolysaccharide (LPS) & during inflammatory processes
• plays a role in the development of endotoxic shock in response to bacterial lipopolysaccharide (LPS) (putative)
• serum levels are high in patients suffering from chronic inflammation

Laboratory

• serum S100A8/A9 may be useful as a marker of inflammation & in the diagnosis of acute appendicitis

More general terms

• calgranulin (MIF-related protein, cystic fibrosis antigen)
• S100 Ca+2-binding protein A

Additional terms

• S100A8/A9 in serum (calprotectin in serum)

Component of

• calprotectin complex (S100A8/A9)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=6279
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6279
• OMIM: https://mirror.omim.org/entry/123885
• UniProt: http://www.uniprot.org/uniprot/P05109.html