Protein S100-A8
Details
- Name
- Protein S100-A8
- Synonyms
- CAGA
- Calgranulin-A
- Calprotectin L1L subunit
- CFAG
- Cystic fibrosis antigen
- Leukocyte L1 complex light chain
- Migration inhibitory factor-related protein 8
- MRP-8
- MRP8
- p8
- S100 calcium-binding protein A8
- Urinary stone protein band A
- Gene Name
- S100A8
- Organism
- Humans
- Amino acid sequence
>lcl|BSEQ0049626|Protein S100-A8 MLTELEKALNSIIDVYHKYSLIKGNFHAVYRDDLKKLLETECPQYIRKKGADVWFKELDI NTDGAVNFQEFLILVIKMGVAAHKKSHEESHKE
- Number of residues
- 93
- Molecular Weight
- 10834.43
- Theoretical pI
- Not Available
- GO Classification
- Functionsarachidonic acid binding / calcium ion binding / microtubule binding / RAGE receptor binding / Toll-like receptor 4 binding / zinc ion bindingProcessesactivation of cysteine-type endopeptidase activity involved in apoptotic process / acute inflammatory response / antimicrobial humoral response / apoptotic process / astrocyte development / autophagy / chemokine production / chronic inflammatory response / cytokine production / defense response to bacterium / defense response to fungus / inflammatory response / innate immune response / leukocyte migration involved in inflammatory response / neutrophil aggregation / neutrophil chemotaxis / neutrophil degranulation / peptidyl-cysteine S-nitrosylation / positive regulation of cell growth / positive regulation of inflammatory response / positive regulation of intrinsic apoptotic signaling pathway / positive regulation of NF-kappaB transcription factor activity / positive regulation of peptide secretion / regulation of cytoskeleton organization / response to ethanol / response to lipopolysaccharide / response to zinc ion / sequestering of zinc ion / toll-like receptor signaling pathway / wound healingComponentscytoskeleton / cytosol / extracellular exosome / extracellular region / extracellular space / intermediate filament cytoskeleton / nucleus / plasma membrane / secretory granule lumen
- General 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. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. The iNOS-S100A8/A9 transnitrosylase complex directs selective inflammatory stimulus-dependent S-nitrosylation of GAPDH and probably multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif; S100A8 seems to contribute to S-nitrosylation site selectivity.
- Specific Function
- Arachidonic acid binding
- Pfam Domain Function
- S_100 (PF01023)
- Transmembrane Regions
- Not Available
- Cellular Location
- Secreted
- Gene sequence
>lcl|BSEQ0049627|Protein S100-A8 (S100A8) ATGTTGACCGAGCTGGAGAAAGCCTTGAACTCTATCATCGACGTCTACCACAAGTACTCC CTGATAAAGGGGAATTTCCATGCCGTCTACAGGGATGACCTGAAGAAATTGCTAGAGACC GAGTGTCCTCAGTATATCAGGAAAAAGGGTGCAGACGTCTGGTTCAAAGAGTTGGATATC AACACTGATGGTGCAGTTAACTTCCAGGAGTTCCTCATTCTGGTGATAAAGATGGGCGTG GCAGCCCACAAAAAAAGCCATGAAGAAAGCCACAAAGAGTAG
- Chromosome Location
- 1
- Locus
- 1q21.3
- External Identifiers
Resource Link UniProtKB ID P05109 UniProtKB Entry Name S10A8_HUMAN HGNC ID HGNC:10498 - General References
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Drug Relations
- Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details DB09130 Copper approved, investigational unknown Details DB01373 Calcium nutraceutical unknown Details DB01593 Zinc approved, investigational unknown Details DB14487 Zinc acetate approved, investigational unknown Details DB14533 Zinc chloride approved, investigational unknown regulator Details DB14548 Zinc sulfate, unspecified form approved, experimental unknown regulator Details