Version 5.4
Bos taurus Protein: S100A8
Summary
InnateDB Protein IDBP-684529.2
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol S100A8
Protein Name Protein S100-A8
Synonyms
Species Bos taurus
Ensembl Protein ENSBTAP00000016774
InnateDB Gene IDBG-632868 (S100A8)
Protein Structure
UniProt Annotation
Function S100A8 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis and adhesion. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH- oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve proinfammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its proinflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF- kappa-B signaling pathways resulting in the amplification of the proinflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants (By similarity). {ECO:0000250}.
Subcellular Localization Secreted {ECO:0000250}. Cytoplasm {ECO:0000250}. Cytoplasm, cytoskeleton {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=Predominantly localized in the cytoplasm. Upon elevation of the intracellular calcium level, translocated from the cytoplasm to the cytoskeleton and the cell membrane. Upon neutrophil activation or endothelial adhesion of monocytes, is secreted via a microtubule-mediated, alternative pathway (By similarity). {ECO:0000250}.
Disease Associations
Tissue Specificity Found essentially in phagocytic cells.
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
Gene Ontology

Molecular Function
Accession GO Term
GO:0005509 calcium ion binding
GO:0005515 protein binding
GO:0008017 microtubule binding
GO:0008270 zinc ion binding
GO:0016209 antioxidant activity
GO:0035662 Toll-like receptor 4 binding
GO:0046872 metal ion binding
GO:0050544 arachidonic acid binding
GO:0050786 RAGE receptor binding
Biological Process
GO:0002376 immune system process
GO:0002523 leukocyte migration involved in inflammatory response
GO:0006914 autophagy
GO:0006915 apoptotic process
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006935 chemotaxis
GO:0006954 inflammatory response
GO:0030593 neutrophil chemotaxis
GO:0045087 innate immune response
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0070488 neutrophil aggregation
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
Cellular Component
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0070062 extracellular vesicular exosome
Protein Structure and Domains
PDB ID
InterPro IPR002048 EF-hand domain
IPR013787 S100/CaBP-9k-type, calcium binding, subdomain
PFAM PF00036
PF13202
PF13405
PF01023
PRINTS
PIRSF
SMART SM00054
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt P28782
PhosphoSite PhosphoSite-
TrEMBL
UniProt Splice Variant
Entrez Gene 616818
UniGene
RefSeq NP_001107197
HUGO
OMIM
CCDS
HPRD
IMGT
EMBL BC111678
GenPept AAI11679

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

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Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca