1. Gene Aliases

S100 Calcium Binding Protein A10, CLP11, P11, ANX2LG, CAL1L, 42C, Annexin II Tetramer (AIIt) P11 Subunit, Cellular Ligand Of Annexin II, Calpactin I Light Chain, Calpactin-1 Light Chain, Protein S100-A10, S100 Calcium-Binding Protein A10 (Annexin II Ligand, Calpactin I, Light Polypeptide (P11)), Annexin II Ligand, Calpactin I, Light Polypeptide, S100 Calcium-Binding Protein A10, Calpactin I, P10 Protein, ANX2L, Ca[1], GP11, P10

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=S100A10&keywords=S100a10]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

The interactions list has been truncated to include only interactions with the strongest support from the literature.

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

Dissolution of Fibrin Clot: The crosslinked fibrin multimers in a clot are broken down to soluble polypeptides by plasmin, a serine protease. Plasmin can be generated from its inactive precursor plasminogen and recruited to the site of a fibrin clot in two ways, by interaction with tissue plasminogen activator at the surface of a fibrin clot, and by interaction with urokinase plasminogen activator at a cell surface. The first mechanism appears to be the major one responsible for the dissolution of clots within blood vessels. The second, although capable of mediating clot dissolution, may normally play a major role in tissue remodeling, cell migration, and inflammation (Chapman 1997; Lijnen 2001).

Clot dissolution is regulated in two ways. First, efficient plasmin activation and fibrinolysis occur only in complexes formed at the clot surface or on a cell membrane - proteins free in the blood are inefficient catalysts and are rapidly inactivated. Second, both plasminogen activators and plasmin itself are inactivated by specific serpins, proteins that bind to serine proteases to form stable, enzymatically inactive complexes (Kohler and Grant 2000).

These events are outlined in the drawing: black arrows connect the substrates (inputs) and products (outputs) of individual reactions, and blue lines connect output activated enzymes to the other reactions that they catalyze [https://reactome.org/PathwayBrowser/#/R-HSA-75205].

GO terms:

mRNA transcription by RNA polymerase II [The cellular synthesis of messenger RNA (mRNA) from a DNA template by RNA polymerase II, originating at an RNA polymerase II promoter. GO:0042789]

membrane raft assembly [The aggregation, arrangement and bonding together of a set of components to form a membrane raft, a small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalizes cellular processes. GO:0001765]

positive regulation of focal adhesion assembly [Any process that activates or increases the frequency, rate or extent of focal adhesion assembly, the establishment and maturation of focal adhesions. GO:0051894]

positive regulation of plasminogen activation [Any process that increases the rate, frequency or extent of plasminogen activation. Plasminogen activation is the process in which plasminogen is processed to plasmin. GO:0010756]

positive regulation of stress fiber assembly [Any process that activates or increases the frequency, rate or extent of the assembly of a stress fiber, a bundle of microfilaments and other proteins found in fibroblasts. GO:0051496]

positive regulation of substrate adhesion-dependent cell spreading [Any process that activates or increases the frequency, rate or extent of substrate adhesion-dependent cell spreading. GO:1900026]

positive regulation of transcription by RNA polymerase II [Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. GO:0045944]

protein localization to plasma membrane [A process in which a protein is transported to, or maintained in, a specific location in the plasma membrane. GO:0072659]

regulation of cell differentiation [Any process that modulates the frequency, rate or extent of cell differentiation, the process in which relatively unspecialized cells acquire specialized structural and functional features. GO:0045595]

regulation of cell growth [Any process that modulates the frequency, rate, extent or direction of cell growth. GO:0001558]

regulation of neurogenesis [Any process that modulates the frequency, rate or extent of neurogenesis, the generation of cells in the nervous system. GO:0050767]

response to xenobiotic stimulus [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. GO:0009410]

vesicle budding from membrane [The evagination of a membrane, resulting in formation of a vesicle. GO:0006900]

MSigDB Signatures:

ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_UP: Genes up-regulated in liver tumor compared to the normal adjacent tissue. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_UP.html]

WIELAND_UP_BY_HBV_INFECTION: Genes induced in the liver during hepatitis B (HBV) viral clearance in chimpanzees. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WIELAND_UP_BY_HBV_INFECTION.html]

ACEVEDO_LIVER_CANCER_UP: Genes up-regulated in hepatocellular carcinoma (HCC) compared to normal liver samples. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ACEVEDO_LIVER_CANCER_UP.html]

PATIL_LIVER_CANCER: Genes up-regulated in hepatocellular carcinoma (HCC) compared to normal liver samples. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/PATIL_LIVER_CANCER.html]

REACTOME_HEMOSTASIS: Hemostasis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_HEMOSTASIS.html]

HSIAO_HOUSEKEEPING_GENES: Housekeeping genes identified as expressed across 19 normal tissues. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/HSIAO_HOUSEKEEPING_GENES.html]

HOSHIDA_LIVER_CANCER_SUBCLASS_S1: Genes from 'subtype S1' signature of hepatocellular carcinoma (HCC): aberrant activation of the WNT signaling pathway. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/HOSHIDA_LIVER_CANCER_SUBCLASS_S1.html]

CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN: Marker genes down-regulated in the 'unannotated' subclass of hepatocellular carcinoma (HCC) samples. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN.html]

WP_PROSTAGLANDIN_SYNTHESIS_AND_REGULATION: Prostaglandin synthesis and regulation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PROSTAGLANDIN_SYNTHESIS_AND_REGULATION.html]

KEGG_MEDICUS_PATHOGEN_SALMONELLA_SOPB_TO_ANXA2_S100A10_REGULATED_ACTIN_CYTOSKELETON: Pathway Definition from KEGG: (SopB,SopE) -> (ANXA2+S100A10) == AHNAK == (ACTB,ACTG1) [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_MEDICUS_PATHOGEN_SALMONELLA_SOPB_TO_ANXA2_S100A10_REGULATED_ACTIN_CYTOSKELETON.html]

REACTOME_DISSOLUTION_OF_FIBRIN_CLOT: Dissolution of Fibrin Clot [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DISSOLUTION_OF_FIBRIN_CLOT.html]

BROWNE_HCMV_INFECTION_24HR_DN: Genes down-regulated in primary fibroblast cell culture after infection with HCMV (AD169 strain) at 24 h time point that were not down-regulated at the previous time point, 20 h. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BROWNE_HCMV_INFECTION_24HR_DN.html]

NABA_SECRETED_FACTORS: Genes encoding secreted soluble factors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NABA_SECRETED_FACTORS.html]

LEE_NEURAL_CREST_STEM_CELL_UP: Genes up-regulated in the neural crest stem cells (NCS), defined as p75+/HNK1+ [GeneID=4804;27087]. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LEE_NEURAL_CREST_STEM_CELL_UP.html]

NABA_MATRISOME_ASSOCIATED: Ensemble of genes encoding ECM-associated proteins including ECM-affilaited proteins, ECM regulators and secreted factors [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NABA_MATRISOME_ASSOCIATED.html]

NABA_MATRISOME_HIGHLY_METASTATIC_BREAST_CANCER: Matrisome proteins exclusively detected in highly metastatic breast cancer human-to-mouse xenografts (MDA-MB-231_LM2) in comparison to poorly metastatic breast cancer human-to-mouse xenografts (MDA-MB-231). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NABA_MATRISOME_HIGHLY_METASTATIC_BREAST_CANCER.html]

SA_FAS_SIGNALING: The TNF-type receptor Fas induces apoptosis on ligand binding. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SA_FAS_SIGNALING.html]

AKL_HTLV1_INFECTION_UP: Genes up-regulated in WE17/10 cells (CD4+ [GeneID=920] T lymphocytes) infected by HTLV1 (and thus displaying low CD7 [GeneID=924]) compared to the uninfected (i.e., CD7+) cells. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/AKL_HTLV1_INFECTION_UP.html]

PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN: Genes down-regulated in HEK-293 cells (fibroblast) upon knockdown of CTBP1 but not of SATB1 [GeneID=1487, 6304] by RNAi. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/PURBEY_TARGETS_OF_CTBP1_NOT_SATB1_DN.html]

LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP: Genes up-regulated in Wilm's tumor samples compared to fetal kidney. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP.html]

LOPEZ_MBD_TARGETS: Genes up-regulated in HeLa cells (cervical cancer) after simultaneus knockdown of all three MBD (methyl-CpG binding domain) proteins MeCP2, MBD1 and MBD2 [GeneID=4204;4152;8932] by RNAi. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/LOPEZ_MBD_TARGETS.html]

VECCHI_GASTRIC_CANCER_EARLY_UP: Up-regulated genes distinguishing between early gastric cancer (EGC) and normal tissue samples. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/VECCHI_GASTRIC_CANCER_EARLY_UP.html]

CHICAS_RB1_TARGETS_CONFLUENT: Genes up-regulated in confluent IMR90 cells (fibroblast) after knockdown of RB1 [GeneID=5925] by RNAi. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/CHICAS_RB1_TARGETS_CONFLUENT.html]

KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3: Genes with promoters occupied by SMAD2 or SMAD3 [GeneID=4087, 4088] in HaCaT cells (keratinocyte) according to a ChIP-chip analysis. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3.html]

7. Gene Descriptions

NCBI Gene Summary: 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 exocytosis and endocytosis. [provided by RefSeq, Jul 2008]

GeneCards Summary: S100A10 (S100 Calcium Binding Protein A10) is a Protein Coding gene. Diseases associated with S100A10 include Trachea Leiomyoma and Conjunctival Intraepithelial Neoplasm. Among its related pathways are Response to elevated platelet cytosolic Ca2+ and Regulation of CFTR activity (norm and CF). Gene Ontology (GO) annotations related to this gene include calcium ion binding and lipid binding. An important paralog of this gene is S100A1.

UniProtKB/Swiss-Prot Summary: Because S100A10 induces the dimerization of ANXA2/p36, it may function as a regulator of protein phosphorylation in that the ANXA2 monomer is the preferred target (in vitro) of tyrosine-specific kinase.

8. Cellular Location of Gene Product

Membranous and cytoplasmic expression in most tissues. Localized to the mitochondria. Predicted location: Membrane [https://www.proteinatlas.org/ENSG00000197747/subcellular]

9. Mechanistic Information

Summary

S100A10, a non-calcium-binding member of the S100 protein family, regulates cellular processes by forming a heterotetrameric complex with annexin A2. This complexation aids in the organization of membrane cytoskeletal compartments [CS: 8] and also mediates the attachment and content delivery of extracellular vesicles (EVs) to target cells [CS: 7]. S100A10-enriched EVs carry proteins like MMP2, fibronectin, and EGF, which are vital for tumor proliferation and metastasis [CS: 8]. These vesicles enhance the stemness of HCC cells and activate signaling pathways such as EGFR, AKT, and ERK, promoting epithelial-mesenchymal transition [CS: 7].

In liver pathologies like steatosis, the upregulation of S100A10, often in response to stressors such as a high-fat diet, appears to be a protective mechanism [CS: 7]. This response likely involves its role in lipid metabolism, where S100A10 aids in managing excess lipids by regulating lipid droplet dynamics, thus preventing lipotoxicity [CS: 6]. Additionally, its interaction with annexin A2 in processes like membrane repair and vesicle trafficking might be crucial in maintaining cellular integrity under stress [CS: 7]. However, this compensatory upregulation becomes counterproductive in the context of hepatocellular carcinoma (HCC), where excessive S100A10 expression contributes to tumor proliferation and invasion [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: esophagus (tissue enhanced) [https://www.proteinatlas.org/ENSG00000197747/tissue]

Cell type enchanced: alveolar cells type 1, distal enterocytes, paneth cells (cell type enhanced) [https://www.proteinatlas.org/ENSG00000197747/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

No biomarkers associated with disease or organ of interest were found