Details for: S100A14

Gene ID: 57402

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: S100A14

Ensembl ID: ENSG00000189334

Description: S100 calcium binding protein A14

Cell Significance Landscape

Associated with

Significant Cells

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

  • keratinocyte CL0000312
    CSI 56.87
    rCSI 47.67%
    PRS 82.37
  • M cell of gut CL0000682
    CSI 41.09
    rCSI 43.65%
    PRS 84.49
  • intestinal epithelial cell CL0002563
    CSI 35.52
    rCSI 37.12%
    PRS 76.91
  • colon epithelial cell CL0011108
    CSI 33.52
    rCSI 35.11%
    PRS 76.78
  • colonocyte CL1000347
    CSI 31.99
    rCSI 45.85%
    PRS 80.17
  • epithelial cell of lung CL0000082
    CSI 26.09
    rCSI 21.63%
    PRS 80.02
  • transit amplifying cell of colon CL0009011
    CSI 23.59
    rCSI 27.71%
    PRS 81.05
  • brush cell CL0002204
    CSI 22.96
    rCSI 45.44%
    PRS 87.99
  • epithelial cell of lower respiratory tract CL0002632
    CSI 20.73
    rCSI 16.07%
    PRS 83.01
  • enterocyte CL0000584
    CSI 20.04
    rCSI 32.31%
    PRS 78.53
  • secretory cell CL0000151
    CSI 19.73
    rCSI 20.59%
    PRS 78.68
  • BEST4+ enteroycte CL4030026
    CSI 17.9
    rCSI 22.26%
    PRS 80.45
  • stem cell CL0000034
    CSI 17.59
    rCSI 16.96%
    PRS 72.54
  • tracheal goblet cell CL1000329
    CSI 17.42
    rCSI 38.03%
    PRS 86.46
  • lung neuroendocrine cell CL1000223
    CSI 17.01
    rCSI 25.16%
    PRS 83.36
  • foveolar cell of stomach CL0002179
    CSI 16.29
    rCSI 34.68%
    PRS 85.72
  • nasal mucosa goblet cell CL0002480
    CSI 15.93
    rCSI 18.47%
    PRS 83.25
  • respiratory suprabasal cell CL4033048
    CSI 15.83
    rCSI 20.3%
    PRS 82.7
  • lung secretory cell CL1000272
    CSI 15.65
    rCSI 38.73%
    PRS 79
  • respiratory hillock cell CL4030023
    CSI 15.4
    rCSI 27.46%
    PRS 87.79
  • ciliated cell CL0000064
    CSI 15.2
    rCSI 24.62%
    PRS 74.37
  • colon goblet cell CL0009039
    CSI 15.18
    rCSI 36.09%
    PRS 84.86
  • intestine goblet cell CL0019031
    CSI 14.44
    rCSI 12.82%
    PRS 77.01
  • goblet cell CL0000160
    CSI 14.2
    rCSI 13.42%
    PRS 78.01
  • ionocyte CL0005006
    CSI 14.01
    rCSI 15.02%
    PRS 80.6
  • mucous neck cell CL0000651
    CSI 13.69
    rCSI 19.73%
    PRS 86.21
  • peripheral nervous system neuron CL2000032
    CSI 12.9
    rCSI 17.57%
    PRS 70.99
  • acinar cell CL0000622
    CSI 12.6
    rCSI 18.48%
    PRS 88.29
  • respiratory basal cell CL0002633
    CSI 12.46
    rCSI 12.91%
    PRS 83.6
  • pulmonary alveolar type 2 cell CL0002063
    CSI 12.08
    rCSI 18.73%
    PRS 83.56
  • mammary gland epithelial cell CL0002327
    CSI 11.79
    rCSI 41.35%
    PRS 87.31
  • epithelial cell CL0000066
    CSI 11.05
    rCSI 16.99%
    PRS 69.07
  • transit amplifying cell CL0009010
    CSI 10.99
    rCSI 16.81%
    PRS 87.73
  • intestinal tuft cell CL0019032
    CSI 10.95
    rCSI 16.73%
    PRS 83.11
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 10.9
    rCSI 15.44%
    PRS 76.05
  • mucus secreting cell CL0000319
    CSI 10.77
    rCSI 17.11%
    PRS 87.87
  • multi-ciliated epithelial cell CL0005012
    CSI 10.33
    rCSI 10.31%
    PRS 73.19
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 10.25
    rCSI 26.51%
    PRS 74.77
  • enteroendocrine cell CL0000164
    CSI 10.17
    rCSI 13.9%
    PRS 79.18
  • luminal epithelial cell of mammary gland CL0002326
    CSI 10.13
    rCSI 18.4%
    PRS 89.42
  • conjunctival epithelial cell CL1000432
    CSI 9.76
    rCSI 14.91%
    PRS 79.61
  • fallopian tube secretory epithelial cell CL4030006
    CSI 9.76
    rCSI 9.4%
    PRS 78.68
  • lung ciliated cell CL1000271
    CSI 9.51
    rCSI 11%
    PRS 71.61
  • basal-myoepithelial cell of mammary gland CL0002324
    CSI 9.44
    rCSI 17.85%
    PRS 90.04
  • club cell CL0000158
    CSI 9.02
    rCSI 13.22%
    PRS 73.85
  • intrahepatic cholangiocyte CL0002538
    CSI 8.99
    rCSI 21.57%
    PRS 83.43
  • enterocyte of epithelium of large intestine CL0002071
    CSI 8.62
    rCSI 45.26%
    PRS 84.97
  • enteroendocrine cell of small intestine CL0009006
    CSI 8.51
    rCSI 18.73%
    PRS 87.12
  • squamous epithelial cell CL0000076
    CSI 8.37
    rCSI 19.88%
    PRS 79.8
  • pulmonary alveolar type 1 cell CL0002062
    CSI 7.95
    rCSI 45.81%
    PRS 76.22
  • mononuclear phagocyte CL0000113
    CSI 7.57
    rCSI 16.67%
    PRS 83.05
  • bronchial goblet cell CL1000312
    CSI 7.33
    rCSI 29.31%
    PRS 87.41
  • dendritic cell CL0000451
    CSI 7.32
    rCSI 9.02%
    PRS 83.61
  • duct epithelial cell CL0000068
    CSI 7.05
    rCSI 10.32%
    PRS 84.03
  • basal cell CL0000646
    CSI 6.62
    rCSI 8.86%
    PRS 78.14
  • epithelial cell of esophagus CL0002252
    CSI 6.58
    rCSI 65.03%
    PRS 85.26
  • basal cell of epidermis CL0002187
    CSI 6.55
    rCSI 11.62%
    PRS 48.96
  • basal cell of prostate epithelium CL0002341
    CSI 6.45
    rCSI 18.65%
    PRS 86.09
  • IgA plasma cell CL0000987
    CSI 5.48
    rCSI 5.61%
    PRS 87.02
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 5.47
    rCSI 14.76%
    PRS 84.28
  • kidney epithelial cell CL0002518
    CSI 5.41
    rCSI 10.33%
    PRS 92.36
  • paneth cell of colon CL0009009
    CSI 5.29
    rCSI 51.93%
    PRS 88.09
  • stratified epithelial cell CL0000079
    CSI 5.17
    rCSI 31.92%
    PRS 88.31
  • type L enteroendocrine cell CL0002279
    CSI 4.74
    rCSI 8.89%
    PRS 86.66
  • corneal epithelial cell CL0000575
    CSI 4.71
    rCSI 13.48%
    PRS 86.2
  • respiratory goblet cell CL0002370
    CSI 4.71
    rCSI 51.21%
    PRS 87.52
  • small intestine goblet cell CL1000495
    CSI 4.48
    rCSI 9.82%
    PRS 85.03
  • deuterosomal cell CL4033044
    CSI 4.42
    rCSI 14.93%
    PRS 77.27
  • transit amplifying cell of small intestine CL0009012
    CSI 4.32
    rCSI 18.97%
    PRS 87.43
  • pancreatic ductal cell CL0002079
    CSI 4.22
    rCSI 8.2%
    PRS 82.3
  • tracheobronchial serous cell CL0019001
    CSI 4.05
    rCSI 17.49%
    PRS 86.4
  • lung goblet cell CL1000143
    CSI 3.99
    rCSI 44.62%
    PRS 88.88
  • glial cell CL0000125
    CSI 3.85
    rCSI 14.68%
    PRS 70.43
  • paneth cell of epithelium of small intestine CL1000343
    CSI 3.62
    rCSI 10.15%
    PRS 86.51
  • luminal cell of prostate epithelium CL0002340
    CSI 3.46
    rCSI 18.62%
    PRS 87.12
  • hair follicular keratinocyte CL2000092
    CSI 3.39
    rCSI 58.98%
    PRS 89.62
  • basal cell of epithelium of trachea CL1000348
    CSI 3.37
    rCSI 23.76%
    PRS 85.46
  • type EC enteroendocrine cell CL0000577
    CSI 3.21
    rCSI 11.38%
    PRS 83.52
  • tuft cell of colon CL0009041
    CSI 3.1
    rCSI 7.21%
    PRS 85.41
  • enteroendocrine cell of colon CL0009042
    CSI 2.44
    rCSI 11.45%
    PRS 87.69
  • epithelial cell of urethra CL1000296
    CSI 2.29
    rCSI 57.56%
    PRS 86.91
  • glandular epithelial cell CL0000150
    CSI 2.16
    rCSI 5.68%
    PRS 90.79
  • intestinal crypt stem cell of colon CL0009043
    CSI 2.12
    rCSI 15.92%
    PRS 89.1
  • respiratory epithelial cell CL0002368
    CSI 2.11
    rCSI 13.02%
    PRS 95.03
  • paneth cell CL0000510
    CSI 1.28
    rCSI 1.9%
    PRS 89.34
  • pancreatic acinar cell CL0002064
    CSI 1.13
    rCSI 1.5%
    PRS 84.91
  • Merkel cell CL0000242
    CSI 0.92
    rCSI 21.32%
    PRS 96.08
  • peptic cell CL0000155
    CSI 0.85
    rCSI 8.35%
    PRS 89.71
  • P/D1 enteroendocrine cell CL0002268
    CSI 0.48
    rCSI 2.61%
    PRS 87.27
  • acinar cell of salivary gland CL0002623
    CSI 0.3
    rCSI 6.9%
    PRS 91.16

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 [S100A14](/details-gene/57402) is a protein-coding gene located on chromosome 1q21.3 that encodes S100 calcium-binding protein A14, a member of the S100 family of proteins. Functionally, it is implicated in a range of cellular processes, including calcium ion homeostasis, regulation of apoptosis, and innate immune responses. Expression data indicate that [S100A14](/details-gene/57402) is a highly significant marker for epithelial cells, particularly those forming barrier tissues such as the skin, gut, and lungs. Its role appears to be pleiotropic, contributing to both cellular proliferation and apoptosis in a context-dependent manner, and it is known to be involved in cancer progression by influencing cell invasion [Link](https://doi.org/10.1074/jbc.m111.326975). ## Cellular Roles and Expression Landscape The expression profile of [S100A14](/details-gene/57402) highlights its critical role in epithelial biology. **Overall**, the gene shows its highest significance in [keratinocytes](/details-cell/CL0000312) (CSI: 56.87), the primary cell type of the epidermis. This enrichment extends to a broad range of epithelial cells lining mucosal surfaces, including [M cells of the gut](/details-cell/CL0000682), [intestinal epithelial cells](/details-cell/CL0002563), [colon epithelial cells](/details-cell/CL0011108), and [epithelial cells of the lung](/details-cell/CL0000082). Its high significance in specialized cells like [transit amplifying cells of the colon](/details-cell/CL0009011) and [secretory cells](/details-cell/CL0000151) such as [tracheal goblet cells](/details-cell/CL1000329) suggests a function in both epithelial renewal and barrier maintenance. This specific expression pattern strongly indicates that [S100A14](/details-gene/57402) is a key component of the molecular machinery governing the function and integrity of the body's primary interfaces with the external environment. ## Pathways and Molecular Function [S100A14](/details-gene/57402) is a calcium-binding protein ([GO:0005509](https://www.ebi.ac.uk/QuickGO/term/GO:0005509)), a defining feature of the S100 family, which allows it to act as a calcium sensor and transducer in cellular signaling. Consistent with its high expression in barrier tissues that are constantly exposed to pathogens, the gene is functionally annotated with roles in the innate immune system. These include [defense response to bacterium](/details-go/GO:0042742) and [response to lipopolysaccharide](/details-go/GO:0032496), potentially mediated through the [Toll-like receptor 4 signaling pathway](/details-go/GO:0034142). As an extracellular protein found in the [extracellular space](/details-go/GO:0005615) and within [extracellular exosomes](/details-go/GO:0070062), [S100A14](/details-gene/57402) appears to function as a signaling molecule. It is involved in the [positive regulation of granulocyte chemotaxis](/details-go/GO:0071624) and [monocyte chemotaxis](/details-go/GO:0090026), suggesting it can act as an alarmin or a damage-associated molecular pattern (DAMP) released by stressed or damaged epithelial cells to recruit immune cells to sites of injury or infection. This is further supported by its annotated function in [chemokine receptor binding](/details-go/GO:0042379). Additionally, literature reports a dual role in regulating cell fate, where it can either stimulate proliferation or induce apoptosis, a process potentially mediated by its interaction with the receptor for advanced glycation end products (RAGE) [Link](https://doi.org/10.1371/journal.pone.0019375). ## Research Directions The dual and context-dependent functions of [S100A14](/details-gene/57402) in cell proliferation, apoptosis, and immunity present several intriguing avenues for future investigation, particularly in the context of cancer and inflammatory diseases of epithelial tissues. ### Proposed Hypotheses 1. **[S100A14](/details-gene/57402) acts as an epithelial alarmin whose concentration dictates the nature of the immune response.** At low concentrations, secreted [S100A14](/details-gene/57402) may primarily recruit monocytes for homeostatic tissue surveillance and repair. At high concentrations, such as those released during significant tissue damage or infection, it may preferentially recruit granulocytes, triggering a potent acute inflammatory response. 2. **The switch between pro-proliferative and pro-apoptotic functions of [S100A14](/details-gene/57402) is determined by the cellular redox state or the post-translational modification status of the RAGE receptor.** In a healthy, reducing environment, the S100A14-RAGE interaction may activate pro-survival pathways like NF-kB, whereas under the oxidative stress characteristic of cancer or inflammation, the interaction could trigger pro-apoptotic signaling cascades. ### Key Experimental Approach To test the first hypothesis regarding concentration-dependent immune cell recruitment, a series of *in vitro* chemotaxis assays could be performed. Primary human [keratinocytes](/details-cell/CL0000312) could be cultured and stimulated with a bacterial mimic like LPS to induce secretion of [S100A14](/details-gene/57402). The conditioned media could then be fractionated or, more directly, recombinant [S100A14](/details-gene/57402) could be used at a range of concentrations (e.g., from picomolar to micromolar) in a Boyden chamber assay. The migratory response of isolated human monocytes versus neutrophils towards these concentration gradients would be quantified, revealing any preferential recruitment patterns. ### Therapeutic Potential The extracellular nature of [S100A14](/details-gene/57402) and its interaction with a surface receptor (RAGE) make it a potentially druggable target. However, its complex, bimodal function presents a significant challenge. In cancers where it promotes invasion and metastasis [Link](https://doi.org/10.1074/jbc.m111.326975), **inhibition** of the S100A14-RAGE signaling axis with monoclonal antibodies or small molecule inhibitors could be a viable strategy. Conversely, in other contexts like oral carcinoma where it has been shown to induce G1-arrest [Link](https://doi.org/10.1016/j.oraloncology.2011.10.001), strategies to enhance its local concentration or signaling could be beneficial. Therefore, the therapeutic utility of targeting [S100A14](/details-gene/57402) is likely to be highly dependent on the specific cancer type and the molecular context of its expression.

Genular Protein ID: 1602323224

Symbol: S10AE_HUMAN

Name: Protein S100-A14

UniProtKB Accession Codes:

Q9HCY8 Q5RHT0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BMRB 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 4 EvolutionaryTrace 1 GO 13 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRIDE 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 3 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11944983

Title: Molecular cloning and characterization of the human S100A14 gene encoding a novel member of the S100 family.

PubMed ID: 11944983

DOI: 10.1006/geno.2002.6744

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: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21559403

Title: S100A14 stimulates cell proliferation and induces cell apoptosis at different concentrations via receptor for advanced glycation end products (RAGE).

PubMed ID: 21559403

DOI: 10.1371/journal.pone.0019375

PubMed ID: 22451655

Title: Involvement of S100A14 protein in cell invasion by affecting expression and function of matrix metalloproteinase (MMP)-2 via p53-dependent transcriptional regulation.

PubMed ID: 22451655

DOI: 10.1074/jbc.m111.326975

PubMed ID: 22032898

Title: S100A14 inhibits proliferation of oral carcinoma derived cells through G1-arrest.

PubMed ID: 22032898

DOI: 10.1016/j.oraloncology.2011.10.001

PubMed ID: 23197251

Title: Solution structure and dynamics of human S100A14.

PubMed ID: 23197251

DOI: 10.1007/s00775-012-0963-3

Sequence Information:

  • Length: 104
  • Mass: 11662
  • Checksum: 97EF31A46B388E79
  • Sequence:
    • MGQCRSANAE DAQEFSDVER AIETLIKNFH QYSVEGGKET LTPSELRDLV TQQLPHLMPS 
NCGLEEKIAN LGSCNDSKLE FRSFWELIGE AAKSVKLERP VRGH