Protein detail

S10A9

Protein S100-A9 (Calgranulin-B) (Calprotectin L1H subunit) (Leukocyte L1 complex heavy chain) (Migration inhibitory factor-related protein 14) (MRP-14) (p14) (S100 calcium-binding protein A9)

Entry name S10A9	UniProt ID P06702	EVMP confidence score 0.72
Supporting publications (n) 19	Transmembrane count	Protein classification Cancer-related genesPlasma proteinsPredicted intracellular proteinsPredicted secreted proteins

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information11

Protein Names

Protein S100-A9 (Calgranulin-B) (Calprotectin L1H subunit) (Leukocyte L1 complex heavy chain) (Migration inhibitory factor-related protein 14) (MRP-14) (p14) (S100 calcium-binding protein A9)

Protein Class (4)

Cancer-related genesPlasma proteinsPredicted intracellular proteinsPredicted secreted proteins

Protein Function (3)

Cancer-related genes:Candidate cancer biomarkers
Predicted secreted proteins
Predicted intracellular proteins

Ensembl

ENSG00000163220

Entrez Gene Symbol

S100A9

Gene Synonym (12)

60B8AGCAGBCFAGCGLBLIAGMAC387MIFMRP-14MRP14NIFP14S100-A9

Gene Description

S100 calcium binding protein A9

Chromosome

Position

153357854-153361023

Supporting publications (n)

EVMP confidence score

0.72

Fluorescence & Localization4

Tissue SpecificintestineCell SpecificColonocytesBlood Cell SpecificneutrophilBlood Lineage Specificgranulocytes

Function & Pathway7

Protein Function (3)

Cancer-related genes:Candidate cancer biomarkers
Predicted secreted proteins
Predicted intracellular proteins

Cellular Component (12)

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Molecular Function (9)

Biological Process (3)

KEGG (2)

Reactome (18)

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Mediation Categories (4)

Clinical-translation mediationFusion and delivery mediationImmune mediationReceptor-signaling mediation

Relations & Evidence36

Enzyme-Mediated Modification (1)

1 record.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
S100A9	MAPK14	Q16539	T	113	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPProtMapperPhosphoSitePhosphoSite_ProtMapper

Ligand-Receptor Signaling (26)

26 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
ligand	ligand	CellTalkDB	Yes	No	Yes	No	No
ligand	ligand	Ramilowski2015	Yes	No	Yes	No	No
ligand	ligand	LRdb	Yes	No	Yes	No	No
innate_immune	ligand	ICELLNET	Yes	No	Yes	No	No
innate_immune_tlr	ligand	ICELLNET	Yes	No	Yes	No	No
ligand	ligand	OmniPath	Yes	No	Yes	No	No

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Regulatory Interaction Network (3)

3 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
S10A9	P06702	TLR4	O00206	Yes	Yes	No	Fantom5_LRdbCellTalkDBiTALKtalklrICELLNETReactome_LRdbSIGNORconnectomeDB2020LRdbRamilowski2015	ICELLNET:17767165 talklr:17767165 connectomeDB2020:17767165 CellTalkDB:17767165 SIGNOR:28137827 Ramilowski2015:17767165 LRdb:17767165
S10A9	P06702	RAGE	Q15109	Yes	Yes	No	InnateDBCellinkerCellTalkDBSIGNOR	Cellinker:28504650 InnateDB:23667563 CellTalkDB:28504650 SIGNOR:28137827
MK14	Q16539	S10A9	P06702	Yes	No	No	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:22230807 PhosphoSite:2478889 PhosphoSite:17429438 PhosphoSite:15905572

Protein Complex Composition (5)

5 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
Calprotectin complex	S100A8 S100A9	P05109 P06702	6:6	CORUMSIGNORComplexPortalPDB	SIGNOR:SIGNOR-C293PDB:5w1fPDB:8sjbintact:EBI-10098681PDB:1xk4CORUM:6826PDB:4ggfPDB:8sjcPDB:4xjkintact:EBI-10098135PDB:7quvPDB:1XK4PDB:4GGFPDB:6ds2	17050004 17553524 25597447 14755292 29890074
S100A9 complex	S100A9	P06702	2	ComplexPortalPDB	PDB:1irjintact:EBI-10099500PDB:5i8nPDB:1IRJPDB:7ui5	15642721 22489132 14755292 23123827
iNOS-S100A8/A9 complex	NOS2 S100A8 S100A9	P05109 P06702 P35228	1:1:1	CORUMComplexPortal	CORUM:6827intact:EBI-10105915	14755292 25417112
	S100A7 S100A8 S100A9	P05109 P06702 P31151	0:0:0	hu.MAP2
	S100A8 S100A9 SUSD3	P05109 P06702 Q96L08	0:0:0	hu.MAP2

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationUltrafiltration / Tangential Flow FiltrationSize Exclusion ChromatographyPolymer Precipitation	Western blotting\|Mass spectrometry\|FACSMass spectrometryR Sequencing	10	29045505 35611462 38168906 39505756 21630462 27894104 29045505 38321535 39558134 34980157

Sequence, Structure & Domains12

Sequences

Length

114

Mass

13,242

Sequence

MTCKMSQLERNIETIINTFHQYSVKLGHPDTLNQGEFKELVRKDLQNFLKKENKNEKVIEHIMEDLDTNADKQLSFEEFIMLMARLTWASHEKMHEGDEGPGHHHKPGLGEGTP

3D Structural Models

Turn

45..49; 95..97; 108..110

Helix

7..23; 34..44; 50..53; 56..66; 76..94

Beta Strand

25..28; 71..74

3D Structure

NMR spectroscopy (2); X-ray crystallography (9)

Domain & Motif Annotations

Compositional Bias

93..102; Basic and acidic residues

Domain (FT)

12..47; EF-hand 1; 54..89; EF-hand 2

Region

93..114; Disordered

Protein Families

S-100 family

Sequence Similarities

Belongs to the S-100 family.

Clinical Relevance9

Disease Involvement

Cancer-related genes

Related Diseases (2)

Lupus erythematosus Prostate cancer

Biomarker

Phase 2; Phase 3

Drug Targets (2)

Clinical trial targetLiterature-reported target

Drugs (2)

PAQUINIMOD TASQUINIMOD

Antibody (3)

HPA004193 CAB009441 CAB080262

Interaction Protein (4)

ENSG00000137486ENSG00000141480ENSG00000143546ENSG00000158828

Interaction Count

Interaction Dataset (2)

intact_biogridbiogrid_bioplex

Supporting Publications18

PMID	Title	Abstract
23585443	Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components.	A key finding of this study was the detection and colocalization of protein complexes EPCAM-CLDN7 and TNIK-RAP2A in colorectal cancer cell exosomes. A major finding was the selective enrichment of metastatic factors (MET, S100A8, S100A9, TNC), signal transduction molecules (EFNB2, JAG1, SRC, TNIK), and lipid raft and lipid raft-associated components (CAV1, FLOT1, FLOT2, PROM1) in exosomes derived from metastatic SW620 cells. Exosomes purified using OptiPrep™ density gradient fractionation were 40-100 nm in diameter, were of a buoyant density ~1.09 g/mL, and displayed stereotypic exosomal markers TSG101, Alix, and CD63.
24295599	Exosomes from myeloid-derived suppressor cells carry biologically active proteins.	The pro-inflammatory proteins S100A8 and S100A9, previously shown to be secreted by MDSC and to be chemotactic for MDSC, are abundant in MDSC-derived exosomes.
27353274	Histopathological assessment of calcification and inflammation of calcific aortic valves from patients with and without diabetes mellitus.	Furthermore, in diabetic patients we found significantly increased expression of annexin II (p=0.04) and annexin V (p=0.04), both of which are thought to play a role in microcalcification formation via apoptosis or extracellular vesicle release.
27748581	Evaluation of Spectral Counting for Relative Quantitation of Proteoforms in Top-Down Proteomics.	Following the evaluation and comparison of these label-free top-down quantitation strategies using spiked proteins, spectral counting, along with normalized chromatographic peak areas and intensities, were used to analyze the complex protein cargo of exosomes shed by myeloid-derived suppressor cells collected under high and low conditions of inflammation, revealing statistically significant differences in abundance for several proteoforms, including the active pro-inflammatory proteins S100A8 and S100A9.
30990781	Comparison of six commercial serum exosome isolation methods suitable for clinical laboratories. Effect in cytokine analysis.	Albumin was present in all exosome extracts analyzed and ApoB in all except those extracted with Exo-Flow and ME. Exosome markers CD63, CD9 and TSG101 were determined by Western blot.
31559140	Granulocytic Myeloid-Derived Suppressor Cells Promote the Stemness of Colorectal Cancer Cells through Exosomal S100A9.	Hypoxia induces G-MDSCs to secrete more exosomes in a hypoxia-inducible factor 1α (HIF-1α)-dependent manner, and respiratory hyperoxia can reduce CRC cells stemness through the inhibition of GM-Exo production. It is found that S100A9, is highly expressed in G-MDSC-derived exosomes, and its blockade suppresses CRC cell stemness and the susceptibility of mice to AOM/DSS-induced colitis-associated colon cancer.
32051051	Electron Microscopy-Based Comparison and Investigation of the Morphology of Exosomes Derived from Hepatocellular Carcinoma Cells Isolated at Different Centrifugal Speeds.	Transforming growth factor signaling bioactive substances (TGF-β1, S100A8, and S100A9) can be found in exosomes by performing Western blotting, showing that the internal content is associated with metastasis of HCC.
32460581	S100A9-RAGE Axis Accelerates Formation of Macrophage-Mediated Extracellular Vesicle Microcalcification in Diabetes Mellitus.	Our goal was to identify that increased S100A9 promotes the release of calcification-prone extracellular vesicles from human macrophages in diabetes mellitus. Recombinant S100A9 induced the expression of proinflammatory and osteogenic factors, as well as the number of extracellular vesicles with high calcific potential (alkaline phosphatase activity, Under hyperglycemic conditions, macrophages release calcific extracellular vesicles through mechanisms involving the S100A9-RAGE axis, thus contributing to the formation of microcalcification within atherosclerotic plaques.
33275138	Elongated neutrophil-derived structures are blood-borne microparticles formed by rolling neutrophils during sepsis.	Unlike neutrophil-derived extracellular vesicles, most ENDS are negative for the tetraspanins CD9, CD63, and CD81.
33338939	Molecular cargo in myeloid-derived suppressor cells and their exosomes.	Bioassays showed that exosomes induce MDSC chemotaxis dependent on S100A8 and S100A9 in their cargo. Surface selective chemistry identified glycoproteins on MDSC and exosome surfaces, including CD47 and thrombospondin 1, which both facilitate exosome-catalyzed chemotaxis.

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