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S100A9
HPA
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  • S100A9
PROTEIN SUMMARY GENE INFORMATION RNA DATA ANTIBODY DATA
Hippocampal formation Amygdala Basal ganglia Midbrain Spinal cord Cerebral cortex Cerebellum Hypothalamus Choroid plexus Retina Thyroid gland Parathyroid gland Adrenal gland Pituitary gland Lung Salivary gland Esophagus Tongue Stomach Rectum Duodenum Small intestine Colon Liver Gallbladder Pancreas Kidney Urinary bladder Testis Epididymis Prostate Seminal vesicle Vagina Breast Cervix Endometrium Fallopian tube Ovary Placenta Heart muscle Skeletal muscle Smooth muscle Adipose tissue Skin Bone marrow Lymph node Thymus Appendix Tonsil Spleen
S100A9 INFORMATION
Proteini

Full gene name according to HGNC.

S100 calcium binding protein A9
Gene namei

Official gene symbol, which is typically a short form of the gene name, according to HGNC.

S100A9 (60B8AG, CAGB, CFAG, CGLB, LIAG, MAC387, MIF, MRP-14, MRP14, NIF, P14, S100-A9)
Protein classi

Assigned HPA protein class(es) for the encoded protein(s).

Cancer-related genes
Plasma proteins
Protein evidence Evidence at protein level (all genes)
Number of transcriptsi

Number of protein-coding transcripts from the gene as defined by Ensembl.

1
Protein interactions Interacting with 4 proteins
PROTEIN EXPRESSION AND LOCALIZATION
Tissue profilei

A summary of the overall protein expression profile across the analyzed normal tissues based on knowledge-based annotation, presented in the Tissue resource.

"Estimation of protein expression could not be performed. View primary data." is shown for genes where available RNA-seq and gene/protein characterization data in combination with immunohistochemistry data has been evaluated as not sufficient to yield a reliable estimation of the protein expression profile.
Selective expression in immune cells and squamous epithelia.
Subcellular locationi

Main subcellular location based on data generated in the subcellular section of the Human Protein Atlas.

Localized to the Plasma membrane, Intermediate filaments, Cytosol
Predicted locationi

All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.

  • Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.

  • Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).

The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.

Secreted, Intracellular (different isoforms)
Extracellular locationi

All genes with at least one isoform expected to be secreted to the extracellular environment have been annotated and classified either as secreted to blood or as locally secreted, depending on the predicted final location of the corresponding protein. Proteins expected to be locally secreted have been further classified according to their site of expression.

Secreted to blood
TISSUE RNA EXPRESSION
Tissue specificityi

The RNA specificity category is based on normalized mRNA expression levels in the consensus dataset, calculated from the RNA expression levels in samples from HPA and GTEX. The categories include: tissue enriched, group enriched, tissue enhanced, low tissue specificity and not detected.

Tissue enhanced (Bone marrow, Esophagus, Vagina)
Tissue expression clusteri

The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Bone marrow - Cell proliferation (mainly)
Brain specificityi

The regional specificity category is based on mRNA expression levels in the analysed brain samples, grouped into 13 main brain regions and calculated for the three different species. All brain expression profiles are based on data from HPA. The specificity categories include: regionally enriched, group enriched, regionally enhanced, low regional specificity and not detected. The classification rules are the same used for the tissue specificity category

Human brain regional enhanced (Cerebral cortex)
Brain expression clusteri

The RNA data was used to cluster genes according to their expression across tissues. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Non-specific - Vasculature (mainly)
CELL TYPE RNA EXPRESSION
Single cell type specificityi

The RNA specificity category is based on mRNA expression levels in the analyzed cell types based on scRNA-seq data from normal tissues. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.

Cell type enriched (Suprabasal keratinocytes)
Single cell type
expression clusteri

The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Suprabasal keratinocytes - Cornification (mainly)
Tissue cell type classificationi

Genes can have enriched specificity in different cell types in one or several tissues, or be enriched in a core cell type that appears in many different tissues.

Core cell type enriched (Neutrophils, Macrophages)
Immune cell specificityi

The RNA specificity category is based on mRNA expression levels in the analyzed samples based on data from HPA. The categories include: cell type enriched, group enriched, cell type enhanced, low cell type specificity and not detected.

Group enriched (neutrophil, classical monocyte)
Immune cell
expression clusteri

The RNA data was used to cluster genes according to their expression across single cell types. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Monocytes & Neutrophils - Degranulation (mainly)
CANCER & CELL LINES
Prognostic summary S100A9 is a prognostic marker in Glioblastoma multiforme, Liver hepatocellular carcinoma, Lung squamous cell carcinoma
Cancer specificityi

Specificity of RNA expression in 17 cancer types is categorized as either cancer enriched, group enriched, cancer enhanced, low cancer specificity and not detected.

Cancer enhanced (Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma, Head and Neck Squamous Cell Carcinoma)
Cell line
expression clusteri

The RNA data was used to cluster genes according to their expression across cell lines. Clusters contain genes that have similar expression patterns, and each cluster has been manually annotated to describe common features in terms of function and specificity.

Squamous epithelial cells - Keratinization (mainly)
Cell line specificityi

RNA specificity category based on RNA sequencing data from cancer cell lines in the Human Protein Atlas grouped according to type of cancer. Genes are classified into six different categories (enriched, group enriched, enhanced, low specificity and not detected) according to their RNA expression levels across the panel of cell lines.

Cancer enhanced (Breast cancer, Head and neck cancer)
PROTEINS IN BLOOD
Secretome annotationi

All genes with at least one predicted secreted isoform have been annotated and classified with the aim to determine if the corresponding protein(s) are:

  • secreted into blood
  • locally secreted
  • or actually being attached to membrane or retained in intracellular locations like mitochondria, endoplasmatic reticulum (ER), Golgi apparatus or lysosomes.

Secreted to blood
Detected in blood by
immunoassayi

The blood-based immunoassay category applies to actively secreted proteins and is based on plasma or serum protein concentrations established with enzyme-linked immunosorbent assays, compiled from a literature search. The categories include: detected and not detected, where detection refers to a concentration found in the literature search.

Yes
Detected in blood by
mass spectrometryi

Detection or not of the gene in blood, based on spectral count estimations from a publicly available mass spectrometry-based plasma proteomics data set obtained from the PeptideAtlas.

Yes
Proximity extension assayi

Detectibility in blood, based on proximity extension assays (Olink) for a longitudinal wellness study covering 76 individuals with six visits during two years.

Read more
Not available
PROTEIN FUNCTION
Protein function (UniProt)i

Useful information about the protein provided by UniProt.

S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response 1, 2, 3, 4, 5, 6, 7. 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 8, 9, 10. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions 11, 12, 13. 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 14, 15. Participates also in regulatory T-cell differentiation together with CD69 16. 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 17, 18. The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities 19, 20. Its pro-inflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration 21, 22. 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) 23. Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the pro-inflammatory cascade 24, 25. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth 26. 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 27. 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 28. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants 29, 30. Can act as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread 31. 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 32. 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 33.... show less
Molecular function (UniProt)i

Keywords assigned by UniProt to proteins due to their particular molecular function.

Antimicrobial, Antioxidant
Biological process (UniProt)i

Keywords assigned by UniProt to proteins because they are involved in a particular biological process.

Apoptosis, Autophagy, Chemotaxis, Immunity, Inflammatory response, Innate immunity
Ligand (UniProt)i

Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.

Calcium, Metal-binding, Zinc
Gene summary (Entrez)i

Useful information about the gene from Entrez

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]... show less

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