S100A9 [The Human Chemical-Genetic Interaction Map Project]

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======= S100A9 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: S100A9
  * **<color #00a2e8>Official Name</color>**: S100 calcium binding protein A9
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6280|6280]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P06702|P06702]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=S100A9&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20S100A9|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/123886|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  S100A9 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, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. 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. Has transnitrosylase activity; in oxidatively-modified low- densitity lipoprotein (LDL(ox))-induced S-nitrosylation of GAPDH on 'Cys-247' proposed to transfer the NO moiety from NOS2/iNOS to GAPDH via its own S-nitrosylated Cys-3. The iNOS-S100A8/A9 transnitrosylase complex is proposed to also direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as ANXA5, EZR, MSN and VIM by recognizing a [IL]-x-C- x-x-[DE] motif. {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:19402754, ECO:0000269|PubMed:19534726, ECO:0000269|PubMed:19935772, ECO:0000269|PubMed:20103766, ECO:0000269|PubMed:21325622, ECO:0000269|PubMed:21487906, ECO:0000269|PubMed:22363402, ECO:0000269|PubMed:22804476, ECO:0000269|PubMed:22808130, ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:8423249}.

<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|
|peptidyl-cysteine S-trans-nitrosylation|
|sequestering of zinc ion|
|arachidonic acid binding|
|Toll-like receptor 4 binding|
|peptidyl-cysteine S-nitrosylation|
|protein nitrosylation|
|chemokine production|
|leukocyte aggregation|
|RAGE receptor binding|
|sequestering of metal ion|
|leukocyte migration involved in inflammatory response|
|antioxidant activity|
|cellular zinc ion homeostasis|
|zinc ion homeostasis|
|defense response to fungus|
|peptidyl-cysteine modification|
|response to fungus|
|leukocyte cell-cell adhesion|
|positive regulation of intrinsic apoptotic signaling pathway|
|antimicrobial humoral immune response mediated by antimicrobial peptide|
|neutrophil chemotaxis|
|activation of cysteine-type endopeptidase activity involved in apoptotic process|
|granulocyte chemotaxis|
|cellular oxidant detoxification|
|neutrophil migration|
|toll-like receptor signaling pathway|
|granulocyte migration|
|cellular detoxification|
|cellular transition metal ion homeostasis|
|antimicrobial humoral response|
|secretory granule lumen|
|detoxification|
|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|
|modification of morphology or physiology of other organism|
|regulation of intrinsic apoptotic signaling pathway|
|maintenance of location|
|positive regulation of cell growth|
|positive regulation of endopeptidase activity|
|positive regulation of apoptotic signaling pathway|
|positive regulation of peptidase activity|
|cell chemotaxis|
|cellular response to toxic substance|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|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 neuron projection development|
|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|
|positive regulation of neuron differentiation|
|leukocyte migration|
|positive regulation of cell projection organization|
|regulation of apoptotic signaling pathway|
|regulation of endopeptidase activity|
|regulation of cell growth|
|regulation of DNA-binding transcription factor activity|
|regulation of peptidase activity|
|regulation of innate immune response|
|cellular divalent inorganic cation homeostasis|
|positive regulation of neurogenesis|
|positive regulation of defense response|
|neutrophil degranulation|
|divalent inorganic cation homeostasis|
|neutrophil activation involved in immune response|
|regulation of neuron projection development|
|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|
|regulation of response to biotic stimulus|
|myeloid cell activation involved in immune response|
|positive regulation of nervous system development|
|regulation of cytoskeleton organization|
|positive regulation of cell development|
|cell junction|
|chemotaxis|
|taxis|
|cellular metal ion homeostasis|
|immune response-activating signal transduction|
|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 neuron differentiation|
|regulation of growth|
|response to bacterium|
|regulation of plasma membrane bounded cell projection organization|
|positive regulation of cell death|
|regulated exocytosis|
|cation homeostasis|
|regulation of cell projection organization|
|inorganic ion homeostasis|
|calcium ion binding|
|regulation of proteolysis|
|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 neurogenesis|
|interspecies interaction between organisms|
|zinc ion binding|
|positive regulation of immune response|
|peptidyl-amino acid modification|
|cellular homeostasis|
|apoptotic process|
|regulation of nervous system development|
|leukocyte activation|
|cell adhesion|
|regulation of cell development|
|biological adhesion|
|defense response to other organism|
|cell migration|
|positive regulation of cell differentiation|
|secretion by cell|
|positive regulation of intracellular signal transduction|
|export from cell|
|programmed cell death|
|cell activation|
|cell motility|
|localization of cell|
|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|
|positive regulation of cellular component organization|
|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 developmental process|
|positive regulation of catalytic activity|
|regulation of response to stress|
|generation of neurons|
|regulation of apoptotic process|
|movement of cell or subcellular component|
|regulation of programmed cell death|
|extracellular space|
|positive regulation of cellular protein metabolic process|
|neurogenesis|
|homeostatic process|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|cellular catabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|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:p:prim1|PRIM1]]|0.506|
</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>**: 16685
    * **<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='S100A9 Expression in NALM6 Cells: -7.68'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>