Browse S100A9

Summary
SymbolS100A9
NameS100 calcium binding protein A9
Aliases LIAG; MRP14; MAC387; CGLB; CAGB; S100 calcium-binding protein A9 (calgranulin B); S100 calcium binding prote ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted. Cytoplasm. Cytoplasm, cytoskeleton. Cell membrane; Peripheral membrane protein. 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.
Domain PF01023 S-100/ICaBP type calcium binding domain
Function

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.

> Gene Ontology
 
Biological Process GO:0001558 regulation of cell growth
GO:0002523 leukocyte migration involved in inflammatory response
GO:0002790 peptide secretion
GO:0002791 regulation of peptide secretion
GO:0002793 positive regulation of peptide secretion
GO:0006417 regulation of translation
GO:0006875 cellular metal ion homeostasis
GO:0006882 cellular zinc ion homeostasis
GO:0006914 autophagy
GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0007009 plasma membrane organization
GO:0007159 leukocyte cell-cell adhesion
GO:0007596 blood coagulation
GO:0007599 hemostasis
GO:0009620 response to fungus
GO:0009636 response to toxic substance
GO:0010001 glial cell differentiation
GO:0010608 posttranscriptional regulation of gene expression
GO:0010950 positive regulation of endopeptidase activity
GO:0010952 positive regulation of peptidase activity
GO:0014002 astrocyte development
GO:0015833 peptide transport
GO:0016049 cell growth
GO:0017014 protein nitrosylation
GO:0018119 peptidyl-cysteine S-nitrosylation
GO:0018198 peptidyl-cysteine modification
GO:0021782 glial cell development
GO:0030193 regulation of blood coagulation
GO:0030194 positive regulation of blood coagulation
GO:0030307 positive regulation of cell growth
GO:0030593 neutrophil chemotaxis
GO:0030595 leukocyte chemotaxis
GO:0031349 positive regulation of defense response
GO:0031532 actin cytoskeleton reorganization
GO:0032103 positive regulation of response to external stimulus
GO:0032119 sequestering of zinc ion
GO:0032602 chemokine production
GO:0034248 regulation of cellular amide metabolic process
GO:0035606 peptidyl-cysteine S-trans-nitrosylation
GO:0042063 gliogenesis
GO:0042742 defense response to bacterium
GO:0042886 amide transport
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0045112 integrin biosynthetic process
GO:0045113 regulation of integrin biosynthetic process
GO:0045862 positive regulation of proteolysis
GO:0045927 positive regulation of growth
GO:0046916 cellular transition metal ion homeostasis
GO:0048708 astrocyte differentiation
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050817 coagulation
GO:0050818 regulation of coagulation
GO:0050820 positive regulation of coagulation
GO:0050832 defense response to fungus
GO:0050878 regulation of body fluid levels
GO:0050900 leukocyte migration
GO:0051047 positive regulation of secretion
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051235 maintenance of location
GO:0051238 sequestering of metal ion
GO:0051493 regulation of cytoskeleton organization
GO:0052547 regulation of peptidase activity
GO:0052548 regulation of endopeptidase activity
GO:0055069 zinc ion homeostasis
GO:0055076 transition metal ion homeostasis
GO:0060326 cell chemotaxis
GO:0061041 regulation of wound healing
GO:0070486 leukocyte aggregation
GO:0070488 neutrophil aggregation
GO:0071621 granulocyte chemotaxis
GO:0072503 cellular divalent inorganic cation homeostasis
GO:0072507 divalent inorganic cation homeostasis
GO:0090087 regulation of peptide transport
GO:0090303 positive regulation of wound healing
GO:0097193 intrinsic apoptotic signaling pathway
GO:0097529 myeloid leukocyte migration
GO:0097530 granulocyte migration
GO:0098542 defense response to other organism
GO:0098754 detoxification
GO:0098869 cellular oxidant detoxification
GO:1900046 regulation of hemostasis
GO:1900048 positive regulation of hemostasis
GO:1903034 regulation of response to wounding
GO:1903036 positive regulation of response to wounding
GO:1903729 regulation of plasma membrane organization
GO:1990266 neutrophil migration
GO:1990748 cellular detoxification
GO:2000116 regulation of cysteine-type endopeptidase activity
GO:2001056 positive regulation of cysteine-type endopeptidase activity
GO:2001233 regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001242 regulation of intrinsic apoptotic signaling pathway
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
Molecular Function GO:0005504 fatty acid binding
GO:0008017 microtubule binding
GO:0015631 tubulin binding
GO:0016209 antioxidant activity
GO:0031406 carboxylic acid binding
GO:0033293 monocarboxylic acid binding
GO:0035325 Toll-like receptor binding
GO:0035662 Toll-like receptor 4 binding
GO:0036041 long-chain fatty acid binding
GO:0043168 anion binding
GO:0050542 icosanoid binding
GO:0050543 icosatetraenoic acid binding
GO:0050544 arachidonic acid binding
GO:0050786 RAGE receptor binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-6803157: Antimicrobial peptides
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-6799990: Metal sequestration by antimicrobial proteins
R-HSA-6798695: Neutrophil degranulation
R-HSA-5686938: Regulation of TLR by endogenous ligand
R-HSA-168898: Toll-Like Receptors Cascades
Summary
SymbolS100A9
NameS100 calcium binding protein A9
Aliases LIAG; MRP14; MAC387; CGLB; CAGB; S100 calcium-binding protein A9 (calgranulin B); S100 calcium binding prote ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between S100A9 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between S100A9 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27006175GlioblastomaInhibit immunity (T cell function)Elevated levels of polymorphonuclear myeloid-derived suppressor cells in patients with glioblastoma highly express S100A8/9 and arginase and suppress T cell function.
26289067MelanomaInhibit immunity (T cell function)Moreover, in nonresponders, moMDSCs produced significantly more nitric oxide, and granulocytic MDSCs expressed higher levels of PD-L1 than these parameters at baseline and in responders, suggesting their enhanced immunosuppressive capacity. Upon the first ipilimumab infusion, nonresponders displayed elevated serum concentrations of S100A8/A9 and HMGB1 that attract and activate MDSCs.
29326691Colon carcinomaInhibit immunity; immunotherapy targetS100a9 has been emerged as an important pro-inflammatory mediator in acute and chronic inflammation, and the aberrant expression of S100a9 also contributes to tumorigenic processes such as cell proliferation, angiogenesis, metastasis, and immune evasion. We previously revealed that S100a8 and S100a9 are highly activated and play an important role in the process of colitis-associated carcinogenesis, which suggests an attractive therapeutic target for ulcerative colitis and related colon cancer. The inflammatory response, tumor cell proliferation, and immune cells infiltration in the colon tissues were suppressed by anti-S100a9 antibody.
23460744Plasma Cell MyelomaInhibit immunity (T cell function)S100A9 knockout (KO) mice, which are deficient in their ability to accumulate MDSC in tumor-bearing hosts, demonstrated reduced MDSC accumulation in BM after injection of MM cells compared with wild-type mice.
28903971Plasma Cell MyelomaInhibit immunity; candidate for immunotherapy targetWe showed that S100A9 acted as a chemoattractant for MM cells and induced MDSCs to express and secrete inflammatory and pro-myeloma cytokines, including TNFα, IL6, and IL10. Our data suggest that extracellular S100A9 promotes MM and that inhibition of S100A9 may have therapeutic benefit.
28092673Melanoma; Lung CarcinomaInhibit immunityMechanistic studies showed that S100A9, a negative regulator of myeloid cell differentiation, was transrepressed by the IRF7 protein. S100A9 knockdown almost completely abrogated the effects of IRF7 deletion on G-MDSC development and tumor metastasis.
24216507Myelodysplastic SyndromeInhibit immunityUsing multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS.
22955317Non-Small Cell Lung CarcinomaInhibit immunityThe ratio of S100A9(+) cells positively correlated with the suppressive ability of the CD11b(+)CD14(+) cells, was associated with poor response to chemotherapy, and predicted shorter progression-free survival. CD14(+)S100A9(+) inflammatory monocytes in patients with NSCLC are a distinct subset of MDSCs, which suppress T cells by arginase, iNOS, and the IL-13/IL-4Rα axis.
25209187colorectal carcinomaInhibit immunityCPT11 also directly affects MDSCs by boosting secretion of proinflammatory cytokines such as TNFa, which is a key MDSC regulator, inducing their differentiation arrest via S100A8/9 and increasing their suppressive activity
23248262Gastric CarcinomaInhibit immunityS100A8/A9 has been identified as a potential target to modulate antitumor immunity by reversing MDSC-mediated immunosuppression. The ability of MDSCs to suppress T lymphocyte response and the effect of S100A8/A9 and RAGE blocking were tested in vitro by (autologous) MLR. GC patients had significantly more MDSCs than healthy individuals. These MDSCs suppressed both T lymphocyte proliferation and IFN-gamma production and had high arginase-I expression.
21969559MelanomaInhibit immunityIndeed, upon manipulation of the melanoma microenvironment with the phosphodiesterase-5 inhibitor sildenafil, we observed reduced levels of numerous inflammatory mediators (e.g., IL-1β, IL-6, VEGF, S100A9) in association with decreased MDSC amounts and immunosuppressive function, indicating an antiinflammatory effect of sildenafil
Summary
SymbolS100A9
NameS100 calcium binding protein A9
Aliases LIAG; MRP14; MAC387; CGLB; CAGB; S100 calcium-binding protein A9 (calgranulin B); S100 calcium binding prote ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of S100A9 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolS100A9
NameS100 calcium binding protein A9
Aliases LIAG; MRP14; MAC387; CGLB; CAGB; S100 calcium-binding protein A9 (calgranulin B); S100 calcium binding prote ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of S100A9 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1540.875
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.1150.73
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)871.10.615
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.2960.701
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.9860.612
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.5760.811
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.4390.6
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.5370.772
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1810.922
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.6250.813
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4750.906
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.4370.147
> Mutation difference between responders and non-responders
 

There is no record.
Summary
SymbolS100A9
NameS100 calcium binding protein A9
Aliases LIAG; MRP14; MAC387; CGLB; CAGB; S100 calcium-binding protein A9 (calgranulin B); S100 calcium binding prote ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of S100A9. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolS100A9
NameS100 calcium binding protein A9
Aliases LIAG; MRP14; MAC387; CGLB; CAGB; S100 calcium-binding protein A9 (calgranulin B); S100 calcium binding prote ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of S100A9. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by S100A9.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolS100A9
NameS100 calcium binding protein A9
Aliases LIAG; MRP14; MAC387; CGLB; CAGB; S100 calcium-binding protein A9 (calgranulin B); S100 calcium binding prote ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of S100A9. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolS100A9
NameS100 calcium binding protein A9
Aliases LIAG; MRP14; MAC387; CGLB; CAGB; S100 calcium-binding protein A9 (calgranulin B); S100 calcium binding prote ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of S100A9 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolS100A9
NameS100 calcium binding protein A9
Aliases LIAG; MRP14; MAC387; CGLB; CAGB; S100 calcium-binding protein A9 (calgranulin B); S100 calcium binding prote ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between S100A9 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolS100A9
NameS100 calcium binding protein A9
Aliases LIAG; MRP14; MAC387; CGLB; CAGB; S100 calcium-binding protein A9 (calgranulin B); S100 calcium binding prote ......
Chromosomal Location1q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting S100A9 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting S100A9.
ID Name Drug Type Targets #Targets
DB01373CalciumSmall MoleculeALPP, AOC1, ATP2C1, BMP4, CACNA1C, CAST, COMP, CP, MGP, PCDH19, PD ......19
DB01593ZincSmall MoleculeA1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......119