Tbio S100A9 Protein S100-A9

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Protein S100-a9

Protein / Calcium-binding Protein / Intracellular Calcium-sensing Protein / Calmodulin / Protein S100-a9

DTO Classes

Protein / Calcium-binding Protein / Intracellular Calcium-sensing Protein / Calmodulin / Protein S100-a9

Protein Summary

Description

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. The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in the inhibition of casein kinase and altered expression of this protein is associated with the disease cystic fibrosis. This antimicrobial protein exhibits antifungal and antibacterial activity. [provided by RefSeq, Nov 2014]

Uniprot Accession IDs

• P06702
• D3DV36
• Q6FGA1
• Q9NYM0
• Q9UCJ1

Gene Name

• S100A9

Ensembl ID

• ENST00000368738
• ENSP00000357727
• ENSG00000163220

Symbol

• CAGB
• CFAG
• MRP14
• MIF
• NIF
• P14
• CAGB
• CFAG
• CGLB
• L1AG
• LIAG
• MRP14
• 60B8AG
• MAC387

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
gene perturbation	0.99
biological process	0.97
protein complex	0.97
small molecule perturbation	0.97
molecular function	0.96

IDG Partner Tools

GlyGen

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 531.65   (req: < 5)

Gene RIFs: 363   (req: <= 3)

Antibodies: 1077   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 531.65   (req: >= 5)

Gene RIFs: 363   (req: > 3)

Antibodies: 1077   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 33

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (5)

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5

1 – 5 of 5

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
monocyte count	EFO_0005091	1	1	1		21.3
matrix metalloproteinase 8 measurement	EFO_0008466	1	1	1		20.2
monocyte percentage of leukocytes	EFO_0007989	2	1	2		8.6
basophil percentage of leukocytes	EFO_0007992	1	1	1		4.6
granulocyte percentage of myeloid white cells	EFO_0007997	1	1	1		0.8

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5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
monocyte count	EFO_0005091	1		21.3
matrix metalloproteinase 8 measurement	EFO_0008466	1		20.2
monocyte percentage of leukocytes	EFO_0007989	2		8.6
basophil percentage of leukocytes	EFO_0007992	1		4.6
granulocyte percentage of myeloid white cells	EFO_0007997	1		0.8

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Protein Data Bank (7)

1 – 5 of 7

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (15)

Reactome (11)

KEGG (1)

PathwayCommons (1)

WikiPathways (2)

Antimicrobial peptides (R-HSA-6803157)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Antimicrobial peptides	89 targets	R-HSA-6803157
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Innate Immune System	1188 targets	R-HSA-168249
Reactome	Metal sequestration by antimicrobial proteins	6 targets	R-HSA-6799990
Reactome	Neutrophil degranulation	543 targets	R-HSA-6798695

Name	Explore in Pharos	Explore in Source
Antimicrobial peptides	89 targets	R-HSA-6803157
Immune System	2246 targets	R-HSA-168256
Innate Immune System	1188 targets	R-HSA-168249
Metal sequestration by antimicrobial proteins	6 targets	R-HSA-6799990
Neutrophil degranulation	543 targets	R-HSA-6798695

Gene Ontology Terms (45)

Functions (7)

Components (12)

Processes (26)

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Items per page:

10

1 – 7 of 7

GO Term	Evidence	Assigned by
arachidonic acid binding	Traceable Author Statement (TAS)	UniProtKB
calcium ion binding	Traceable Author Statement (TAS)	UniProtKB
microtubule binding	Traceable Author Statement (TAS)	UniProtKB
RAGE receptor binding	Traceable Author Statement (TAS)	UniProtKB
Toll-like receptor 4 binding	Traceable Author Statement (TAS)	UniProtKB
zinc ion binding	Traceable Author Statement (TAS)	UniProtKB
antioxidant activity	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (146)

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1 – 10 of 146

• See Interactions on String-DB

TTC39A

Tdark

Novelty: 0.9151453

p_int: 0.999999995

p_ni: 5e-9

Data Source: BioPlex

GNPAT

Tchem

Family: Enzyme

Novelty: 0.01255689

p_int: 0.99950791

p_ni: 0.00049209

Data Source: BioPlex

NME2P1

Tdark

Family: Kinase

p_int: 0.996911238

p_ni: 0.003088762

Data Source: BioPlex

TTC4

Tbio

Novelty: 0.00808711

p_int: 0.986578706

p_ni: 0.013421294

Data Source: BioPlex

TBC1D22B

Tbio

Novelty: 0.49852962

p_int: 0.954061316

p_ni: 0.045938684

Data Source: BioPlex

PCYOX1

Tbio

Family: Enzyme

Novelty: 0.18505748

p_int: 0.937383014

p_ni: 0.062616986

Data Source: BioPlex

PDE4DIP

Tbio

Novelty: 0.03414104

p_int: 0.930002279

p_ni: 0.069997721

Data Source: BioPlex

PI4KA

Tchem

Family: Kinase

Novelty: 0.01701469

p_int: 0.929092774

p_ni: 0.070907226

Data Source: BioPlex

SUSD3

Tdark

Novelty: 0.43699506

p_int: 0.897039958

p_ni: 0.102960042

Score: 0.208

Data Source: BioPlex,STRINGDB

DDX19B

Tbio

Family: Enzyme

Novelty: 0.0504568

p_int: 0.870608509

p_ni: 0.129391491

Data Source: BioPlex

Publication Statistics

PubMed Score  531.65

PubMed score by year

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PubTator Score  660.32

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Antimicrobial
Antioxidant
Apoptosis
Autophagy
Calcium
Cell membrane
Chemotaxis
Complete proteome
Cytoplasm

GWAS Trait Find Similar Targets

basophil percentage of leukocytes
granulocyte percentage of myeloid white cells
matrix metalloproteinase 8 measurement
monocyte count
monocyte percentage of leukocytes

MGI Phenotype Find Similar Targets

cellular phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging