Browse S100A8

Summary
SymbolS100A8
NameS100 calcium binding protein A8
Aliases CGLA; CAGA; S100 calcium-binding protein A8 (calgranulin A); S100 calcium binding protein A8 (calgranulin A) ......
Chromosomal Location1q12-q22
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

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.

> Gene Ontology
 
Biological Process GO:0001558 regulation of cell growth
GO:0002237 response to molecule of bacterial origin
GO:0002523 leukocyte migration involved in inflammatory response
GO:0002526 acute inflammatory response
GO:0002544 chronic inflammatory response
GO:0002790 peptide secretion
GO:0002791 regulation of peptide secretion
GO:0002793 positive regulation of peptide secretion
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:0007159 leukocyte cell-cell adhesion
GO:0009620 response to fungus
GO:0010001 glial cell differentiation
GO:0010035 response to inorganic substance
GO:0010038 response to metal ion
GO:0010043 response to zinc ion
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:0030307 positive regulation of cell growth
GO:0030593 neutrophil chemotaxis
GO:0030595 leukocyte chemotaxis
GO:0031349 positive regulation of defense response
GO:0032103 positive regulation of response to external stimulus
GO:0032119 sequestering of zinc ion
GO:0032496 response to lipopolysaccharide
GO:0032602 chemokine production
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:0045471 response to ethanol
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:0050832 defense response to fungus
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: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:0097193 intrinsic apoptotic signaling pathway
GO:0097305 response to alcohol
GO:0097529 myeloid leukocyte migration
GO:0097530 granulocyte migration
GO:0098542 defense response to other organism
GO:1990266 neutrophil migration
GO:1990267 response to transition metal nanoparticle
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: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
SymbolS100A8
NameS100 calcium binding protein A8
Aliases CGLA; CAGA; S100 calcium-binding protein A8 (calgranulin A); S100 calcium binding protein A8 (calgranulin A) ......
Chromosomal Location1q12-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between S100A8 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 S100A8 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.
29675003Gastric CarcinomaInhibit immunityExosomes have been shown to deliver not only various types of genetic information, mainly miRNAs, but also cytotoxin-associated gene A (CagA), a major H. pylori virulence factor.
18802069Breast CarcinomaInhibit immunityS100A8/A9 proteins bind to carboxylated N-glycans expressed on the receptor for advanced glycation end-products and other cell surface glycoprotein receptors on MDSC, signal through the NF-kappaB pathway, and promote MDSC migration.
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.
Summary
SymbolS100A8
NameS100 calcium binding protein A8
Aliases CGLA; CAGA; S100 calcium-binding protein A8 (calgranulin A); S100 calcium binding protein A8 (calgranulin A) ......
Chromosomal Location1q12-q22
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 S100A8 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
SymbolS100A8
NameS100 calcium binding protein A8
Aliases CGLA; CAGA; S100 calcium-binding protein A8 (calgranulin A); S100 calcium binding protein A8 (calgranulin A) ......
Chromosomal Location1q12-q22
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 S100A8 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.4790.677
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.8690.768
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)871.4880.46
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0330.969
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-1.3350.343
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 471.770.332
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.4560.632
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.6890.682
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0080.996
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.7790.747
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4360.906
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.5220.16
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of S100A8 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolS100A8
NameS100 calcium binding protein A8
Aliases CGLA; CAGA; S100 calcium-binding protein A8 (calgranulin A); S100 calcium binding protein A8 (calgranulin A) ......
Chromosomal Location1q12-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of S100A8. 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
SymbolS100A8
NameS100 calcium binding protein A8
Aliases CGLA; CAGA; S100 calcium-binding protein A8 (calgranulin A); S100 calcium binding protein A8 (calgranulin A) ......
Chromosomal Location1q12-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of S100A8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by S100A8.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolS100A8
NameS100 calcium binding protein A8
Aliases CGLA; CAGA; S100 calcium-binding protein A8 (calgranulin A); S100 calcium binding protein A8 (calgranulin A) ......
Chromosomal Location1q12-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of S100A8. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolS100A8
NameS100 calcium binding protein A8
Aliases CGLA; CAGA; S100 calcium-binding protein A8 (calgranulin A); S100 calcium binding protein A8 (calgranulin A) ......
Chromosomal Location1q12-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of S100A8 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolS100A8
NameS100 calcium binding protein A8
Aliases CGLA; CAGA; S100 calcium-binding protein A8 (calgranulin A); S100 calcium binding protein A8 (calgranulin A) ......
Chromosomal Location1q12-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between S100A8 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolS100A8
NameS100 calcium binding protein A8
Aliases CGLA; CAGA; S100 calcium-binding protein A8 (calgranulin A); S100 calcium binding protein A8 (calgranulin A) ......
Chromosomal Location1q12-q22
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting S100A8 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting S100A8.
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
DB09130CopperSmall MoleculeA1BG, ACTG1, ACTN1, ACY1, AFM, AGT, AHCY, AHSG, AKR1A1, ANXA4, ANX ......141