Details for: S100Z

Gene ID: 170591

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: S100Z

Ensembl ID: ENSG00000171643

Description: S100 calcium binding protein Z

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • mononuclear phagocyte CL0000113
    CSI 10.35
    rCSI 22.78%
    PRS 97.58
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 10.19
    rCSI 7.85%
    PRS 98
  • CD14-positive monocyte CL0001054
    CSI 4.88
    rCSI 6.07%
    PRS 98.8
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 4.81
    rCSI 28.34%
    PRS 89.57
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 3.26
    rCSI 8.51%
    PRS 97.3
  • common myeloid progenitor CL0000049
    CSI 3.05
    rCSI 2.47%
    PRS 97.08
  • intermediate monocyte CL0002393
    CSI 2.57
    rCSI 3.88%
    PRS 98.26
  • early lymphoid progenitor CL0000936
    CSI 2.57
    rCSI 2.26%
    PRS 97.85
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.52
    rCSI 2.19%
    PRS 97.15
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 1.94
    rCSI 2.35%
    PRS 98.33
  • myeloid dendritic cell CL0000782
    CSI 1.88
    rCSI 2.72%
    PRS 99.25
  • Hofbauer cell CL3000001
    CSI 1.81
    rCSI 3.41%
    PRS 98.28
  • central nervous system macrophage CL0000878
    CSI 1.77
    rCSI 5.87%
    PRS 96.56

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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  • Node Color (Target Cell CSI, relative to current network):
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    • 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 [S100Z](/details-gene/170591) is a protein-coding gene located on chromosome 5 that belongs to the S100 family of EF-hand calcium-binding proteins ([Link](https://pubmed.ncbi.nlm.nih.gov/11747429/)). As a calcium-binding protein, its primary molecular functions, as annotated by Gene Ontology, include [calcium ion binding](/details-cell/GO:0005509) and [calcium-dependent protein binding](/details-cell/GO:0048306). Expression data indicates that [S100Z](/details-gene/170591) is a highly significant marker for cells of the myeloid lineage, particularly [mononuclear phagocyte](/details-cell/CL0000113)s and various monocyte subsets. This expression pattern suggests a key role in the innate immune system, likely related to calcium-mediated signaling processes within these cells. ## Cellular Roles and Expression Landscape The expression profile of [S100Z](/details-gene/170591) strongly implicates it in the function of the mononuclear phagocyte system. **Overall**, it demonstrates the highest significance in [mononuclear phagocyte](/details-cell/CL0000113) (CSI: 10.35) and specifically in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 10.19) and [CD14-positive monocyte](/details-cell/CL0001054) (CSI: 4.88). This pattern is consistent across different states of myeloid cell development and differentiation, with significant expression also noted in progenitor cells like the [common myeloid progenitor](/details-cell/CL0000049) and [granulocyte monocyte progenitor cell](/details-cell/CL0000557). Furthermore, its significance extends to tissue-resident and specialized macrophage populations, including [kidney interstitial alternatively activated macrophage](/details-cell/CL1000695), [Hofbauer cell](/details-cell/CL3000001)s (placental macrophages), and [central nervous system macrophage](/details-cell/CL0000878)s. The gene also serves as a marker for [myeloid dendritic cell](/details-cell/CL0000782)s, reinforcing its role within professional antigen-presenting cells of the innate immune system. Interestingly, a high CSI score was also observed in [corticothalamic-projecting glutamatergic cortical neuron](/details-cell/CL4023013), suggesting a potential, albeit less characterized, role in a specific neuronal subtype outside of the immune context. ## Pathways and Molecular Function The molecular function of [S100Z](/details-gene/170591) is centered on its ability to bind calcium and subsequently interact with other proteins. This is defined by its GO annotations for [calcium ion binding](/details-cell/GO:0005509), [calcium-dependent protein binding](/details-cell/GO:0048306), and general [protein binding](/details-cell/GO:0005515). The protein is also capable of self-association, as indicated by its role in [protein homodimerization activity](/details-cell/GO:0042803) ([Link](https://doi.org/10.1007/s00775-017-1437-4)). In the context of the highly expressing myeloid cells, this calcium-binding function is likely integral to intracellular signaling cascades that govern key cellular processes such as phagocytosis, migration, and the inflammatory response, which are all heavily dependent on precise calcium flux regulation. ## Research Directions The specific expression pattern and molecular function of [S100Z](/details-gene/170591) lead to several testable hypotheses and potential avenues for therapeutic exploration. **Proposed Hypotheses:** 1. Given its high expression in monocytes and macrophages, [S100Z](/details-gene/170591) may act as an intracellular calcium sensor that regulates inflammatory cytokine production (e.g., TNF-alpha, IL-6) or inflammasome activation in response to pathogenic stimuli. 2. The distinct and high expression of [S100Z](/details-gene/170591) in [corticothalamic-projecting glutamatergic cortical neuron](/details-cell/CL4023013) suggests a specialized function in neuronal calcium homeostasis, potentially modulating synaptic transmission or plasticity in this specific neural circuit. **Experimental Approach:** To investigate the first hypothesis regarding its role in inflammation, a targeted knockout of [S100Z](/details-gene/170591) could be performed in primary human monocytes or a monocytic cell line (e.g., THP-1) using CRISPR-Cas9. These cells would then be differentiated into macrophages and challenged with inflammatory agonists like lipopolysaccharide (LPS). The impact of [S100Z](/details-gene/170591) deletion could be assessed by measuring changes in intracellular calcium signaling using fluorescent indicators, quantifying cytokine secretion with ELISA or Luminex assays, and evaluating the expression of key inflammatory genes via RT-qPCR or RNA-sequencing. **Therapeutic Potential:** As S100 proteins are frequently dysregulated in inflammatory diseases and cancer, [S100Z](/details-gene/170591) presents a potential therapeutic target. Its high specificity for myeloid lineage cells suggests that targeting it could modulate innate immune responses with potentially fewer off-target effects on other cell types. **Inhibition** of [S100Z](/details-gene/170591) function, perhaps using a small molecule that disrupts its calcium-binding pocket or its interaction with downstream protein partners, could be a viable strategy to ameliorate diseases driven by hyper-activation of monocytes and macrophages, such as rheumatoid arthritis or sepsis.

Genular Protein ID: 559392075

Symbol: S100Z_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8WXG8

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 9 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 3 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 RNAct 1 RefSeq 9 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 neXtProt 1

Citations:

PubMed ID: 11747429

Title: Molecular characterization and tissue distribution of a novel member of the S100 family of EF-hand proteins.

PubMed ID: 11747429

DOI: 10.1021/bi0114731

PubMed ID: 15372022

Title: The DNA sequence and comparative analysis of human chromosome 5.

PubMed ID: 15372022

DOI: 10.1038/nature02919

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: 28074300

Title: Solving the crystal structure of human calcium-free S100Z: the siege and conquer of one of the last S100 family strongholds.

PubMed ID: 28074300

DOI: 10.1007/s00775-017-1437-4

Sequence Information:

  • Length: 99
  • Mass: 11620
  • Checksum: 2D019EE19C68E994
  • Sequence:
    • MPTQLEMAMD TMIRIFHRYS GKERKRFKLS KGELKLLLQR ELTEFLSCQK ETQLVDKIVQ 
DLDANKDNEV DFNEFVVMVA ALTVACNDYF VEQLKKKGK