======= S100A8 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: S100A8
  * **<color #00a2e8>Official Name</color>**: S100 calcium binding protein A8
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6279|6279]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P05109|P05109]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=S100A8&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20S100A8|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/123885|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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 proinflammatory, 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. {ECO:0000269|PubMed:12626582, ECO:0000269|PubMed:15331440, ECO:0000269|PubMed:15598812, ECO:0000269|PubMed:15642721, ECO:0000269|PubMed:16258195, ECO:0000269|PubMed:19087201, ECO:0000269|PubMed:19122197, ECO:0000269|PubMed:19935772, ECO:0000269|PubMed:21487906, ECO:0000269|PubMed:22363402, ECO:0000269|PubMed:22808130, ECO:0000269|PubMed:25417112}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|S 100|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|neutrophil aggregation|
|sequestering of zinc ion|
|arachidonic acid binding|
|Toll-like receptor 4 binding|
|peptidyl-cysteine S-nitrosylation|
|protein nitrosylation|
|autocrine signaling|
|chemokine production|
|leukocyte aggregation|
|chronic inflammatory response|
|RAGE receptor binding|
|sequestering of metal ion|
|leukocyte migration involved in inflammatory response|
|cellular zinc ion homeostasis|
|astrocyte development|
|zinc ion homeostasis|
|defense response to fungus|
|peptidyl-cysteine modification|
|intermediate filament cytoskeleton|
|response to fungus|
|leukocyte cell-cell adhesion|
|astrocyte differentiation|
|response to zinc ion|
|positive regulation of intrinsic apoptotic signaling pathway|
|acute inflammatory response|
|neutrophil chemotaxis|
|activation of cysteine-type endopeptidase activity involved in apoptotic process|
|granulocyte chemotaxis|
|neutrophil migration|
|toll-like receptor signaling pathway|
|granulocyte migration|
|glial cell development|
|cellular transition metal ion homeostasis|
|antimicrobial humoral response|
|secretory granule lumen|
|response to ethanol|
|myeloid leukocyte migration|
|pattern recognition receptor signaling pathway|
|transition metal ion homeostasis|
|positive regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|positive regulation of inflammatory response|
|leukocyte chemotaxis|
|cytokine production|
|positive regulation of cysteine-type endopeptidase activity|
|positive regulation of NF-kappaB transcription factor activity|
|regulation of intrinsic apoptotic signaling pathway|
|maintenance of location|
|positive regulation of cell growth|
|glial cell differentiation|
|positive regulation of endopeptidase activity|
|positive regulation of apoptotic signaling pathway|
|positive regulation of peptidase activity|
|cell chemotaxis|
|gliogenesis|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|response to alcohol|
|innate immune response-activating signal transduction|
|microtubule binding|
|regulation of cysteine-type endopeptidase activity|
|activation of innate immune response|
|positive regulation of growth|
|autophagy|
|process utilizing autophagic mechanism|
|positive regulation of DNA-binding transcription factor activity|
|positive regulation of peptide secretion|
|response to antibiotic|
|response to lipopolysaccharide|
|response to molecule of bacterial origin|
|defense response to bacterium|
|regulation of inflammatory response|
|positive regulation of innate immune response|
|humoral immune response|
|positive regulation of proteolysis|
|positive regulation of response to biotic stimulus|
|collagen-containing extracellular matrix|
|cytoskeleton|
|response to metal ion|
|leukocyte migration|
|regulation of apoptotic signaling pathway|
|regulation of endopeptidase activity|
|regulation of cell growth|
|regulation of DNA-binding transcription factor activity|
|positive regulation of secretion|
|regulation of peptidase activity|
|regulation of innate immune response|
|cellular divalent inorganic cation homeostasis|
|positive regulation of defense response|
|wound healing|
|neutrophil degranulation|
|divalent inorganic cation homeostasis|
|neutrophil activation involved in immune response|
|regulation of peptide secretion|
|neutrophil mediated immunity|
|inflammatory response|
|neutrophil activation|
|granulocyte activation|
|cell-cell adhesion|
|response to toxic substance|
|positive regulation of multi-organism process|
|leukocyte degranulation|
|myeloid leukocyte mediated immunity|
|myeloid cell activation involved in immune response|
|regulation of response to biotic stimulus|
|response to inorganic substance|
|regulation of cytoskeleton organization|
|chemotaxis|
|taxis|
|cellular metal ion homeostasis|
|immune response-activating signal transduction|
|response to wounding|
|myeloid leukocyte activation|
|immune response-regulating signaling pathway|
|positive regulation of response to external stimulus|
|leukocyte activation involved in immune response|
|metal ion homeostasis|
|cell activation involved in immune response|
|activation of immune response|
|cellular cation homeostasis|
|positive regulation of apoptotic process|
|cellular ion homeostasis|
|positive regulation of programmed cell death|
|regulation of growth|
|response to bacterium|
|positive regulation of cell death|
|regulated exocytosis|
|cation homeostasis|
|inorganic ion homeostasis|
|calcium ion binding|
|regulation of proteolysis|
|regulation of peptide transport|
|cellular chemical homeostasis|
|regulation of defense response|
|leukocyte mediated immunity|
|innate immune response|
|positive regulation of hydrolase activity|
|regulation of multi-organism process|
|ion homeostasis|
|exocytosis|
|regulation of secretion|
|zinc ion binding|
|response to lipid|
|positive regulation of immune response|
|peptidyl-amino acid modification|
|cellular homeostasis|
|apoptotic process|
|leukocyte activation|
|cell adhesion|
|biological adhesion|
|defense response to other organism|
|cell migration|
|central nervous system development|
|positive regulation of transport|
|secretion by cell|
|positive regulation of intracellular signal transduction|
|response to drug|
|export from cell|
|programmed cell death|
|cell activation|
|localization of cell|
|cell motility|
|cell death|
|immune effector process|
|regulation of response to external stimulus|
|chemical homeostasis|
|cell-cell signaling|
|secretion|
|positive regulation of immune system process|
|regulation of immune response|
|regulation of hydrolase activity|
|regulation of organelle organization|
|response to other organism|
|response to external biotic stimulus|
|locomotion|
|response to biotic stimulus|
|defense response|
|positive regulation of catalytic activity|
|regulation of response to stress|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|response to oxygen-containing compound|
|regulation of programmed cell death|
|extracellular space|
|positive regulation of cellular protein metabolic process|
|neurogenesis|
|homeostatic process|
|cell development|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|positive regulation of protein metabolic process|
|positive regulation of molecular function|
|cellular catabolic process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of transport|
|immune response|
|extracellular region|
|vesicle-mediated transport|
</modal>
\\

 === CRISPR Data ===
<button type='default' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
No hits were found.
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:r:rrm1|RRM1]]|0.486|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 17985
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: -7.68 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='S100A8 Expression in NALM6 Cells: -7.68'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>