Details for: S100A2

Gene ID: 6273

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: S100A2

Ensembl ID: ENSG00000196754

Description: S100 calcium binding protein A2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • respiratory suprabasal cell CL4033048
    CSI 54.5
    rCSI 69.89%
    PRS 93.45
  • keratinocyte CL0000312
    CSI 52.86
    rCSI 44.31%
    PRS 91.87
  • respiratory basal cell CL0002633
    CSI 50.05
    rCSI 51.85%
    PRS 93.43
  • respiratory hillock cell CL4030023
    CSI 41.07
    rCSI 73.23%
    PRS 95.15
  • conjunctival epithelial cell CL1000432
    CSI 32.17
    rCSI 49.14%
    PRS 91.2
  • epithelial cell of lower respiratory tract CL0002632
    CSI 18.15
    rCSI 14.07%
    PRS 93.99
  • basal cell of prostate epithelium CL0002341
    CSI 16.13
    rCSI 46.68%
    PRS 94.04
  • basal cell CL0000646
    CSI 15.79
    rCSI 21.12%
    PRS 89.71
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 15.13
    rCSI 18.33%
    PRS 73.84
  • nasal mucosa goblet cell CL0002480
    CSI 14.45
    rCSI 16.76%
    PRS 92.29
  • secretory cell CL0000151
    CSI 12.89
    rCSI 13.45%
    PRS 91.17
  • epithelial cell of lung CL0000082
    CSI 10.75
    rCSI 8.91%
    PRS 92.92
  • acinar cell CL0000622
    CSI 10.46
    rCSI 15.34%
    PRS 96.13
  • airway submucosal gland duct basal cell CL4033024
    CSI 9.76
    rCSI 62.43%
    PRS 93.1
  • duct epithelial cell CL0000068
    CSI 9.73
    rCSI 14.24%
    PRS 94.86
  • epithelial cell CL0000066
    CSI 9.69
    rCSI 14.89%
    PRS 80.87
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 9.59
    rCSI 21.87%
    PRS 85.71
  • innate lymphoid cell CL0001065
    CSI 9.28
    rCSI 19.17%
    PRS 86.42
  • basal cell of epithelium of trachea CL1000348
    CSI 8.99
    rCSI 63.46%
    PRS 92.59
  • ionocyte CL0005006
    CSI 8.96
    rCSI 9.6%
    PRS 93.22
  • fallopian tube secretory epithelial cell CL4030006
    CSI 8.6
    rCSI 8.28%
    PRS 90.81
  • basal-myoepithelial cell of mammary gland CL0002324
    CSI 8.34
    rCSI 15.77%
    PRS 96.49
  • multi-ciliated epithelial cell CL0005012
    CSI 8.18
    rCSI 8.17%
    PRS 87.04
  • skin fibroblast CL0002620
    CSI 7.82
    rCSI 6.74%
    PRS 91.6
  • tracheobronchial serous cell CL0019001
    CSI 7.7
    rCSI 33.27%
    PRS 93.88
  • renal beta-intercalated cell CL0002201
    CSI 7.57
    rCSI 18.03%
    PRS 92.3
  • kidney collecting duct principal cell CL1001431
    CSI 7.35
    rCSI 36.99%
    PRS 87.8
  • bronchial goblet cell CL1000312
    CSI 6.96
    rCSI 27.8%
    PRS 94.62
  • helper T cell CL0000912
    CSI 6.77
    rCSI 9.57%
    PRS 87.85
  • epithelial cell of esophagus CL0002252
    CSI 6.57
    rCSI 64.91%
    PRS 90.99
  • tracheal goblet cell CL1000329
    CSI 6.41
    rCSI 13.99%
    PRS 93.84
  • squamous epithelial cell CL0000076
    CSI 6.38
    rCSI 15.14%
    PRS 89.17
  • club cell CL0000158
    CSI 6.32
    rCSI 9.25%
    PRS 88.31
  • myoepithelial cell CL0000185
    CSI 6.24
    rCSI 15.78%
    PRS 93.94
  • epithelial cell of proximal tubule CL0002306
    CSI 6.01
    rCSI 14.68%
    PRS 86.5
  • lung secretory cell CL1000272
    CSI 5.63
    rCSI 13.93%
    PRS 93
  • kidney collecting duct intercalated cell CL1001432
    CSI 4.49
    rCSI 32.08%
    PRS 88.89
  • stratified epithelial cell CL0000079
    CSI 4.24
    rCSI 26.17%
    PRS 94.35
  • mammary gland epithelial cell CL0002327
    CSI 4.21
    rCSI 14.77%
    PRS 95.39
  • renal principal cell CL0005009
    CSI 4.16
    rCSI 10.81%
    PRS 91.7
  • melanocyte of skin CL1000458
    CSI 4.13
    rCSI 5.63%
    PRS 64.61
  • mucus secreting cell CL0000319
    CSI 3.68
    rCSI 5.85%
    PRS 95.55
  • hair follicular keratinocyte CL2000092
    CSI 3.59
    rCSI 62.46%
    PRS 94.59
  • kidney connecting tubule epithelial cell CL1000768
    CSI 3.59
    rCSI 9.1%
    PRS 87.08
  • lung ciliated cell CL1000271
    CSI 3.45
    rCSI 3.99%
    PRS 87.24
  • pulmonary alveolar type 1 cell CL0002062
    CSI 3.25
    rCSI 18.74%
    PRS 89.87
  • mononuclear phagocyte CL0000113
    CSI 3.04
    rCSI 6.7%
    PRS 94.36
  • cytotoxic T cell CL0000910
    CSI 2.9
    rCSI 16.61%
    PRS 90.67
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 2.81
    rCSI 24.31%
    PRS 87.32
  • epithelial cell of urethra CL1000296
    CSI 2.58
    rCSI 65.06%
    PRS 93.86
  • dendritic cell CL0000451
    CSI 2.51
    rCSI 3.09%
    PRS 91.58
  • pulmonary ionocyte CL0017000
    CSI 2.49
    rCSI 3.03%
    PRS 94.9
  • basal cell of epidermis CL0002187
    CSI 2.47
    rCSI 4.38%
    PRS 64.96
  • deuterosomal cell CL4033044
    CSI 2.36
    rCSI 7.99%
    PRS 86.87
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.29
    rCSI 3.24%
    PRS 90.52
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.14
    rCSI 5.53%
    PRS 90.04
  • Merkel cell CL0000242
    CSI 2
    rCSI 46.41%
    PRS 98.17
  • glandular epithelial cell CL0000150
    CSI 1.88
    rCSI 4.96%
    PRS 97.02
  • stem cell CL0000034
    CSI 1.85
    rCSI 1.78%
    PRS 88.44
  • suprabasal keratinocyte CL4033013
    CSI 1.79
    rCSI 2.93%
    PRS 64.94
  • respiratory goblet cell CL0002370
    CSI 1.73
    rCSI 18.81%
    PRS 94.2
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 1.25
    rCSI 13.21%
    PRS 88.89
  • luminal cell of prostate epithelium CL0002340
    CSI 1.22
    rCSI 6.59%
    PRS 95.04
  • kidney granular cell CL0000648
    CSI 1.13
    rCSI 16.33%
    PRS 92.58
  • kidney connecting tubule principal cell CL4030018
    CSI 1.06
    rCSI 7.69%
    PRS 91.57
  • macula densa epithelial cell CL1000850
    CSI 0.9
    rCSI 12.86%
    PRS 90.87

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [S100A2](/details-gene/6273) is a protein-coding gene located on chromosome 1q21.3 that encodes S100 calcium-binding protein A2, a member of the S100 family of EF-hand calcium-binding proteins. Functionally, it is involved in calcium-dependent signal transduction by binding calcium ions and subsequently interacting with other proteins. Expression data highlights its prominent role in various epithelial tissues, with particularly high significance in [keratinocytes](/details-cell/CL0000312) and respiratory epithelial cells. Research has identified [S100A2](/details-gene/6273) as a candidate tumor suppressor gene, as its expression is frequently downregulated in certain cancers, such as mammary carcinoma, often through epigenetic mechanisms like DNA hypermethylation ([Link](https://doi.org/10.1073/pnas.89.6.2504), [Link](https://doi.org/10.1016/s0143-4160(97)90063-4)). Its clinical relevance is noted under OMIM entry [176993](https://omim.org/entry/176993). ## Cellular Roles and Expression Landscape The expression profile of [S100A2](/details-gene/6273) strongly indicates a primary function in epithelial cell biology, particularly in stratified and respiratory epithelia. **Overall**, the gene shows the highest significance in cell types responsible for forming barrier and secretory surfaces. - **Epithelial and Keratinocyte Identity:** The gene is a defining marker for multiple epithelial cell subtypes. It exhibits its highest significance in [respiratory suprabasal cell](/details-cell/CL4033048) (CSI: 54.50), [keratinocyte](/details-cell/CL0000312) (CSI: 52.86), and [respiratory basal cell](/details-cell/CL0002633) (CSI: 50.05). This high expression in both basal and suprabasal layers suggests a role throughout the epithelial differentiation program. Its significance extends to other specialized epithelial cells including [respiratory hillock cell](/details-cell/CL4030023) (CSI: 41.07), [conjunctival epithelial cell](/details-cell/CL1000432) (CSI: 32.17), and [basal cell of prostate epithelium](/details-cell/CL0002341) (CSI: 16.13). The identification of [S100A2](/details-gene/6273) in the proteome of normal human epidermal keratinocytes further solidifies this association ([Link](https://doi.org/10.1002/elps.11501301199)). - **Role in Secretory and Glandular Tissues:** Beyond barrier epithelia, [S100A2](/details-gene/6273) is also significantly expressed in various secretory cells, such as [nasal mucosa goblet cell](/details-cell/CL0002480) (CSI: 14.45), [secretory cell](/details-cell/CL0000151) (CSI: 12.89), and [acinar cell](/details-cell/CL0000622) (CSI: 10.46), suggesting a role in glandular function and secretion processes. - **Minor Immune Context:** While predominantly an epithelial marker, [S100A2](/details-gene/6273) also shows moderate significance in [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 15.13), which may indicate a secondary role within specific subsets of the adaptive immune system. ## Pathways and Molecular Function The functions of [S100A2](/details-gene/6273) are intrinsically linked to calcium signaling and protein-protein interactions. Its molecular activities, as defined by Gene Ontology, are consistent with its role as a transducer of intracellular calcium signals. - **Molecular Function (GO):** The primary molecular function of the [S100A2](/details-gene/6273) protein is `[Calcium ion binding](/details-go/GO:0005509)`, which enables it to act as a calcium sensor. Upon calcium binding, it undergoes a conformational change that facilitates `[Calcium-dependent protein binding](/details-go/GO:0048306)`. It also engages in `[Identical protein binding](/details-go/GO:0042802)`, suggesting it can form homodimers, and binds other transition metal ions ([`Transition metal ion binding`](/details-go/GO:0046914)). The protein has been shown to interact with targets such as protein phosphatase 5 and tubulin polymerization-promoting protein, linking calcium signals to dephosphorylation and cytoskeletal regulation, respectively ([Link](https://doi.org/10.1074/jbc.m111.329771), [Link](https://doi.org/10.1016/j.ceca.2021.102404)). - **Biological Process (GO):** At the process level, [S100A2](/details-gene/6273) is annotated for its involvement in `[Endothelial cell migration](/details-go/GO:0043542)`. This function, coupled with its high expression in epithelial cells, suggests a potential role in modulating cell motility during processes like wound healing, tissue morphogenesis, or cancer metastasis. ## Research Directions The existing data, particularly the strong link between [S100A2](/details-gene/6273) downregulation and cancer, provides a clear basis for further investigation into its role as a tumor suppressor in epithelial tissues. **Proposed Hypotheses:** 1. Given its extremely high significance in respiratory epithelial cells and its established epigenetic silencing in breast cancer, it is hypothesized that promoter hypermethylation of [S100A2](/details-gene/6273) is a frequent and early event in the pathogenesis of lung squamous cell carcinoma, leading to loss of its tumor-suppressive function and promoting malignant transformation. 2. Based on its role in `[Endothelial cell migration](/details-go/GO:0043542)` and its function as a calcium-dependent regulator of the cytoskeleton, it is hypothesized that [S100A2](/details-gene/6273) is essential for proper epithelial wound healing. Its loss in chronic non-healing wounds or fibrotic conditions may impair the coordinated migration and differentiation of keratinocytes required for re-epithelialization. **Experimental Approach:** To test the first hypothesis regarding its role in lung cancer, a multi-faceted study could be conducted. Initially, a cohort of patient-derived lung squamous cell carcinoma tumors and matched normal adjacent tissue would be analyzed. Quantitative PCR and immunohistochemistry would be used to confirm the downregulation of [S100A2](/details-gene/6273) at the mRNA and protein levels in tumor samples. Concurrently, bisulfite sequencing of the [S100A2](/details-gene/6273) promoter region would be performed to correlate its expression status with DNA methylation levels. For functional validation, lung cancer cell lines with low endogenous [S100A2](/details-gene/6273) expression and high promoter methylation could be treated with a demethylating agent like 5-azacytidine to induce re-expression. Alternatively, these cells could be engineered to stably re-express [S100A2](/details-gene/6273) via lentiviral transduction. The effect of its restored expression on key cancer hallmarks, such as cell proliferation (e.g., via BrdU incorporation assays), migration (e.g., via transwell assays), and invasion, would then be assessed. **Therapeutic Potential:** As a candidate tumor suppressor that is epigenetically silenced rather than mutated, [S100A2](/details-gene/6273) is a promising target for therapeutic reactivation. The primary strategy would not be inhibition but rather restoring its natural expression in cancer cells. This could be achieved using epigenetic drugs, such as DNA methyltransferase (DNMT) inhibitors, which have been shown to re-express [S100A2](/details-gene/6273) in mammary carcinoma cells ([Link](https://doi.org/10.1073/pnas.89.6.2504)). Such an approach could potentially restore its tumor-suppressive functions and increase the sensitivity of tumors to conventional chemotherapies.

Genular Protein ID: 2796343446

Symbol: S10A2_HUMAN

Name: Protein S100-A2

UniProtKB Accession Codes:

P29034 O00266 Q3KRB9 Q5RHS8 Q9BU83

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTAC 1 CPTC 1 CTD 1 ChEBI 7 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 7 EMBL 5 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 5 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 PRIDE 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1372446

Title: Down-regulation of a member of the S100 gene family in mammary carcinoma cells and reexpression by azadeoxycytidine treatment.

PubMed ID: 1372446

DOI: 10.1073/pnas.89.6.2504

PubMed ID: 9481475

Title: Repression of the candidate tumor suppressor gene S100A2 in breast cancer is mediated by site-specific hypermethylation.

PubMed ID: 9481475

DOI: 10.1016/s0143-4160(97)90063-4

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 1286667

Title: Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes.

PubMed ID: 1286667

DOI: 10.1002/elps.11501301199

PubMed ID: 20188096

Title: S100 proteins regulate the interaction of Hsp90 with cyclophilin 40 and FKBP52 through their tetratricopeptide repeats.

PubMed ID: 20188096

DOI: 10.1016/j.febslet.2010.02.055

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 22399290

Title: S100 proteins modulate protein phosphatase 5 function: a link between CA2+ signal transduction and protein dephosphorylation.

PubMed ID: 22399290

DOI: 10.1074/jbc.m111.329771

PubMed ID: 18394645

Title: Crystal structure of Ca2+ -free S100A2 at 1.6-A resolution.

PubMed ID: 18394645

DOI: 10.1016/j.jmb.2008.03.019

PubMed ID: 33831707

Title: Regulation of the tubulin polymerization-promoting protein by Ca2+/S100 proteins.

PubMed ID: 33831707

DOI: 10.1016/j.ceca.2021.102404

Sequence Information:

  • Length: 98
  • Mass: 11117
  • Checksum: 56D09548450142A9
  • Sequence:
    • MMCSSLEQAL AVLVTTFHKY SCQEGDKFKL SKGEMKELLH KELPSFVGEK VDEEGLKKLM 
GSLDENSDQQ VDFQEYAVFL ALITVMCNDF FQGCPDRP