Details for: EHF

Gene ID: 26298

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: EHF

Ensembl ID: ENSG00000135373

Description: ETS homologous factor

Cell Significance Landscape

Associated with

Significant Cells

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

  • conjunctival epithelial cell CL1000432
    CSI 43.43
    rCSI 66.33%
    PRS 86.25
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 23.2
    rCSI 32.88%
    PRS 83.64
  • duct epithelial cell CL0000068
    CSI 21.01
    rCSI 30.73%
    PRS 90.45
  • respiratory suprabasal cell CL4033048
    CSI 15.79
    rCSI 20.25%
    PRS 88.74
  • acinar cell CL0000622
    CSI 15.35
    rCSI 22.5%
    PRS 93.26
  • colonocyte CL1000347
    CSI 14.74
    rCSI 21.13%
    PRS 85.57
  • epithelial cell of lower respiratory tract CL0002632
    CSI 13.5
    rCSI 10.47%
    PRS 89.59
  • tuft cell of colon CL0009041
    CSI 13.36
    rCSI 31.13%
    PRS 89.92
  • ciliated epithelial cell CL0000067
    CSI 12.37
    rCSI 10.88%
    PRS 76.94
  • IgA plasma cell CL0000987
    CSI 11.74
    rCSI 12.02%
    PRS 90.41
  • corneal epithelial cell CL0000575
    CSI 11.33
    rCSI 32.4%
    PRS 89.84
  • nasal mucosa goblet cell CL0002480
    CSI 10.68
    rCSI 12.38%
    PRS 88.33
  • enteroendocrine cell CL0000164
    CSI 10.39
    rCSI 14.2%
    PRS 85.43
  • ionocyte CL0005006
    CSI 9.37
    rCSI 10.04%
    PRS 88.37
  • respiratory basal cell CL0002633
    CSI 9.04
    rCSI 9.36%
    PRS 89.07
  • kidney connecting tubule epithelial cell CL1000768
    CSI 8.73
    rCSI 22.14%
    PRS 78.61
  • secretory cell CL0000151
    CSI 8.69
    rCSI 9.07%
    PRS 85.49
  • epithelial cell CL0000066
    CSI 8.61
    rCSI 13.22%
    PRS 74.98
  • BEST4+ enteroycte CL4030026
    CSI 8.45
    rCSI 10.51%
    PRS 86.6
  • pulmonary alveolar type 2 cell CL0002063
    CSI 8.37
    rCSI 12.99%
    PRS 88.48
  • fallopian tube secretory epithelial cell CL4030006
    CSI 8.31
    rCSI 8%
    PRS 85.59
  • glandular epithelial cell CL0000150
    CSI 8.05
    rCSI 21.2%
    PRS 94.23
  • pulmonary alveolar type 1 cell CL0002062
    CSI 8.02
    rCSI 46.24%
    PRS 83.04
  • intestine goblet cell CL0019031
    CSI 7.9
    rCSI 7.01%
    PRS 83.93
  • multi-ciliated epithelial cell CL0005012
    CSI 7.57
    rCSI 7.55%
    PRS 80.73
  • epithelial cell of lung CL0000082
    CSI 7.53
    rCSI 6.24%
    PRS 87.47
  • lung ciliated cell CL1000271
    CSI 7.4
    rCSI 8.56%
    PRS 80.1
  • enterocyte of epithelium of large intestine CL0002071
    CSI 7.33
    rCSI 38.49%
    PRS 89.56
  • pancreatic D cell CL0000173
    CSI 7.18
    rCSI 7.06%
    PRS 88.24
  • serous secreting cell of bronchus submucosal gland CL4033005
    CSI 7.15
    rCSI 40.68%
    PRS 90.39
  • tracheobronchial serous cell CL0019001
    CSI 6.88
    rCSI 29.71%
    PRS 90.5
  • renal principal cell CL0005009
    CSI 6.63
    rCSI 17.23%
    PRS 86.1
  • brush cell of tracheobronchial tree CL0002075
    CSI 6.59
    rCSI 19.55%
    PRS 93.04
  • ciliated cell CL0000064
    CSI 6.52
    rCSI 10.56%
    PRS 81.07
  • transit amplifying cell of colon CL0009011
    CSI 6.46
    rCSI 7.58%
    PRS 87.33
  • intestinal tuft cell CL0019032
    CSI 6.39
    rCSI 9.77%
    PRS 88.97
  • lung neuroendocrine cell CL1000223
    CSI 6.38
    rCSI 9.44%
    PRS 88.87
  • goblet cell CL0000160
    CSI 6.3
    rCSI 5.95%
    PRS 84.52
  • club cell CL0000158
    CSI 6.01
    rCSI 8.8%
    PRS 81.48
  • pulmonary ionocyte CL0017000
    CSI 5.74
    rCSI 6.99%
    PRS 91.17
  • serous secreting cell CL0000313
    CSI 5.66
    rCSI 28.63%
    PRS 93.57
  • respiratory hillock cell CL4030023
    CSI 5.6
    rCSI 9.98%
    PRS 91.82
  • respiratory goblet cell CL0002370
    CSI 5.45
    rCSI 59.27%
    PRS 91.1
  • squamous epithelial cell CL0000076
    CSI 5.4
    rCSI 12.8%
    PRS 85
  • stem cell CL0000034
    CSI 5.29
    rCSI 5.1%
    PRS 81.37
  • basal cell CL0000646
    CSI 5.07
    rCSI 6.78%
    PRS 84.05
  • airway submucosal gland duct basal cell CL4033024
    CSI 5.02
    rCSI 32.11%
    PRS 89.1
  • brush cell CL0002204
    CSI 4.96
    rCSI 9.82%
    PRS 91.35
  • myoepithelial cell CL0000185
    CSI 4.85
    rCSI 12.27%
    PRS 89.7
  • mucous neck cell CL0000651
    CSI 4.66
    rCSI 6.72%
    PRS 90.69
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 4.55
    rCSI 11.76%
    PRS 82.83
  • colon epithelial cell CL0011108
    CSI 4.18
    rCSI 4.38%
    PRS 83.98
  • colon goblet cell CL0009039
    CSI 3.96
    rCSI 9.41%
    PRS 89.53
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 3.9
    rCSI 10.52%
    PRS 89.4
  • intestinal crypt stem cell of colon CL0009043
    CSI 3.56
    rCSI 26.77%
    PRS 92.84
  • deuterosomal cell CL4033044
    CSI 3.53
    rCSI 11.95%
    PRS 82.16
  • transit amplifying cell CL0009010
    CSI 3.45
    rCSI 5.27%
    PRS 91.45
  • keratinocyte CL0000312
    CSI 3.31
    rCSI 2.78%
    PRS 87.97
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 3.28
    rCSI 7.48%
    PRS 79.63
  • pancreatic ductal cell CL0002079
    CSI 3.23
    rCSI 6.28%
    PRS 88.8
  • type L enteroendocrine cell CL0002279
    CSI 3.11
    rCSI 5.84%
    PRS 90
  • lung secretory cell CL1000272
    CSI 3.03
    rCSI 7.5%
    PRS 86.93
  • mammary gland epithelial cell CL0002327
    CSI 2.95
    rCSI 10.36%
    PRS 91.64
  • lung goblet cell CL1000143
    CSI 2.9
    rCSI 32.44%
    PRS 91.5
  • mucus secreting cell CL0000319
    CSI 2.89
    rCSI 4.59%
    PRS 92.25
  • acinar cell of salivary gland CL0002623
    CSI 2.86
    rCSI 66.54%
    PRS 93.66
  • paneth cell of epithelium of small intestine CL1000343
    CSI 2.81
    rCSI 7.87%
    PRS 90.8
  • intestinal epithelial cell CL0002563
    CSI 2.67
    rCSI 2.79%
    PRS 84.02
  • intrahepatic cholangiocyte CL0002538
    CSI 2.62
    rCSI 6.29%
    PRS 88.25
  • paneth cell CL0000510
    CSI 2.48
    rCSI 3.66%
    PRS 93.13
  • foveolar cell of stomach CL0002179
    CSI 2.37
    rCSI 5.04%
    PRS 89.94
  • transit amplifying cell of small intestine CL0009012
    CSI 2.31
    rCSI 10.13%
    PRS 91.4
  • small intestine goblet cell CL1000495
    CSI 2.11
    rCSI 4.61%
    PRS 89.92
  • stratified epithelial cell CL0000079
    CSI 2.08
    rCSI 12.81%
    PRS 91.28
  • M cell of gut CL0000682
    CSI 1.91
    rCSI 2.03%
    PRS 89.36
  • tracheal goblet cell CL1000329
    CSI 1.81
    rCSI 3.95%
    PRS 90.51
  • luminal epithelial cell of mammary gland CL0002326
    CSI 1.77
    rCSI 3.22%
    PRS 93.02
  • basal cell of prostate epithelium CL0002341
    CSI 1.6
    rCSI 4.62%
    PRS 90.56
  • bronchial goblet cell CL1000312
    CSI 1.36
    rCSI 5.42%
    PRS 91.05
  • pancreatic acinar cell CL0002064
    CSI 1.33
    rCSI 1.77%
    PRS 90.53
  • epithelial cell of esophagus CL0002252
    CSI 1.27
    rCSI 12.57%
    PRS 87.91
  • basal cell of epithelium of trachea CL1000348
    CSI 1.19
    rCSI 8.37%
    PRS 88.7
  • enterocyte of epithelium of small intestine CL1000334
    CSI 1.1
    rCSI 17%
    PRS 90.88
  • respiratory epithelial cell CL0002368
    CSI 0.92
    rCSI 5.69%
    PRS 96.73
  • pancreatic PP cell CL0002275
    CSI 0.86
    rCSI 3.41%
    PRS 91.13
  • luminal cell of prostate epithelium CL0002340
    CSI 0.63
    rCSI 3.4%
    PRS 91.86

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 [EHF](/details-gene/26298) (ETS Homologous Factor) is a protein-coding gene located on chromosome 11p13. It encodes a transcription factor belonging to the E26 transformation-specific (ETS) family, a group of proteins characterized by a conserved DNA-binding domain. As a nuclear protein, [EHF](/details-gene/26298) functions primarily as a sequence-specific DNA-binding transcription activator, regulating gene expression by binding to chromatin. Its expression profile is highly specific to epithelial tissues, where it plays a critical role in cellular differentiation and maintenance. Publications suggest it functions as an epithelium-specific ETS factor, often referred to as ESE-3 ([Link](https://doi.org/10.1074/jbc.275.4.2986)), and its transcriptional activity can be context-dependent, sometimes acting as a repressor downstream of MAPK signaling pathways ([Link](https://doi.org/10.1074/jbc.m010930200)). ## Cellular Roles and Expression Landscape The expression pattern of [EHF](/details-gene/26298) underscores its essential role in establishing and maintaining diverse epithelial cell populations. **Overall**, the gene shows the highest significance in cells forming barrier and secretory surfaces across multiple organ systems. It is most prominently expressed in [conjunctival epithelial cell](/details-cell/CL1000432) (CSI: 43.43), indicating a critical function in the ocular surface. High significance is also observed in specialized epithelial cells of the kidney, such as the [kidney loop of Henle thin descending limb epithelial cell](/details-cell/CL1001111) (CSI: 23.20), and various glandular and mucosal epithelia, including [duct epithelial cell](/details-cell/CL0000068) (CSI: 21.01), [acinar cell](/details-cell/CL0000622) (CSI: 15.35), and [colonocyte](/details-cell/CL1000347) (CSI: 14.74). Its widespread importance in respiratory epithelia is highlighted by its significance in [respiratory suprabasal cell](/details-cell/CL4033048), [epithelial cell of lower respiratory tract](/details-cell/CL0002632), [ciliated epithelial cell](/details-cell/CL0000067), and [nasal mucosa goblet cell](/details-cell/CL0002480). This is consistent with studies demonstrating its constitutive and cytokine-induced expression in the lung ([Link](https://doi.org/10.1165/rcmb.2002-0011oc)). Beyond a purely epithelial role, a notable significance in [IgA plasma cell](/details-cell/CL0000987) (CSI: 11.74) suggests a potential function in mucosal immunity. Furthermore, research indicates its involvement in the development of monocyte-derived dendritic cells, pointing to a broader role in the immune system that may bridge epithelial defense and professional antigen presentation ([Link](https://doi.org/10.1182/blood-2005-06-2480)). ## Pathways and Molecular Function Functionally, [EHF](/details-gene/26298) is annotated as a transcription factor with specific roles in regulating gene expression. Its molecular functions are centered on its ability to interact with DNA and other proteins within the [nucleus](/details-cell/GO:0005634) and [nucleoplasm](/details-cell/GO:0005654). Key molecular activities include [Dna binding](/details-cell/GO:0003677) and more specifically, [Dna-binding transcription activator activity, rna polymerase ii-specific](/details-cell/GO:0001228), facilitating the [positive regulation of transcription by rna polymerase ii](/details-cell/GO:0045944). This core function drives its involvement in major biological processes, most notably [cell differentiation](/details-cell/GO:0030154), with a pronounced role in [epithelial cell differentiation](/details-cell/GO:0030855). Mechanistically, [EHF](/details-gene/26298) has been shown to be a downstream effector of the MAPK signaling cascade, where it can act as a transcriptional repressor depending on the cellular context ([Link](https://doi.org/10.1074/jbc.m010930200)). This suggests that its activity is not static but is dynamically regulated by extracellular signals. Additionally, it has been implicated in regulating apoptosis through the transcriptional control of Death Receptor-5 (DR5), linking its function to pathways of programmed cell death ([Link](https://doi.org/10.1016/j.bbrc.2006.09.102)). ## Research Directions The specific and high-level expression of [EHF](/details-gene/26298) in various epithelial tissues, combined with its known regulatory functions, presents several avenues for future investigation. Its role as a context-dependent transcription factor downstream of major signaling pathways makes it a potentially critical node in epithelial homeostasis and disease. Based on the available data, several testable hypotheses can be proposed: 1. Given its high expression in mucosal epithelial cells (e.g., [conjunctival epithelial cell](/details-cell/CL1000432), [colonocyte](/details-cell/CL1000347)) and its documented induction by cytokines ([Link](https://doi.org/10.1165/rcmb.2002-0011oc)), [EHF](/details-gene/26298) may function as a master regulator of epithelial barrier integrity and innate immune responses during inflammation or infection. 2. The observation that [EHF](/details-gene/26298) is involved in both epithelial differentiation and dendritic cell development ([Link](https://doi.org/10.1182/blood-2005-06-2480)) suggests it may control a common transcriptional program related to cell-cell communication at mucosal interfaces, potentially influencing how epithelial cells prime dendritic cell responses to pathogens or allergens. To test the first hypothesis regarding its role in barrier function, a key experiment could be performed. Using primary human bronchial epithelial cells grown in an air-liquid interface (ALI) culture system, which mimics the in vivo respiratory epithelium, one could specifically knock down [EHF](/details-gene/26298) using shRNA or CRISPR interference (CRISPRi). Following knockdown, the epithelial monolayers would be challenged with an inflammatory stimulus such as poly(I:C) or TNF-alpha. The impact on barrier function could be quantified by measuring transepithelial electrical resistance (TEER), while changes in the inflammatory secretome (e.g., IL-6, IL-8, CCL20) could be assessed by ELISA or multiplex assay. As a therapeutic target, [EHF](/details-gene/26298) presents both opportunities and challenges. Its nature as a transcription factor makes it difficult to target directly with small molecule inhibitors. However, its high tissue specificity is advantageous, suggesting that modulating its activity could have limited off-target effects. For diseases characterized by epithelial dysfunction, such as inflammatory bowel disease or chronic obstructive pulmonary disease, the therapeutic strategy might involve indirectly targeting upstream kinases (e.g., MAPK pathway components) that regulate [EHF](/details-gene/26298) activity or developing biologics that disrupt its interaction with essential co-activators or co-repressors.

Genular Protein ID: 139532679

Symbol: EHF_HUMAN

Name: ETS homologous factor

UniProtKB Accession Codes:

Q9NZC4 D3DR08 D3DR10 E9PSB2 Q9H509 Q9UKF9 Q9Y5V4 Q9Y5V5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 16 Ensembl 5 ExpressionAtlas 1 GO 11 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 RefSeq 7 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10527851

Title: Human chromosomal localization, tissue/tumor expression, and regulatory function of the ets family gene EHF.

PubMed ID: 10527851

DOI: 10.1006/bbrc.1999.1493

PubMed ID: 10644770

Title: ESE-3, a novel member of an epithelium-specific ets transcription factor subfamily, demonstrates different target gene specificity from ESE-1.

PubMed ID: 10644770

DOI: 10.1074/jbc.275.4.2986

PubMed ID: 11259407

Title: The epithelium-specific ETS protein EHF/ESE-3 is a context-dependent transcriptional repressor downstream of MAPK signaling cascades.

PubMed ID: 11259407

DOI: 10.1074/jbc.m010930200

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

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: 12444029

Title: Constitutive and cytokine-induced expression of the ETS transcription factor ESE-3 in the lung.

PubMed ID: 12444029

DOI: 10.1165/rcmb.2002-0011oc

PubMed ID: 17027647

Title: ESE-3 transcription factor is involved in the expression of death receptor (DR)-5 through putative Ets sites.

PubMed ID: 17027647

DOI: 10.1016/j.bbrc.2006.09.102

PubMed ID: 16380452

Title: Epithelial-specific transcription factor ESE-3 is involved in the development of monocyte-derived DCs.

PubMed ID: 16380452

DOI: 10.1182/blood-2005-06-2480

Sequence Information:

  • Length: 300
  • Mass: 34892
  • Checksum: 5CABB38BAF852ED0
  • Sequence:
    • MILEGGGVMN LNPGNNLLHQ PPAWTDSYST CNVSSGFFGG QWHEIHPQYW TKYQVWEWLQ 
HLLDTNQLDA NCIPFQEFDI NGEHLCSMSL QEFTRAAGTA GQLLYSNLQH LKWNGQCSSD 
LFQSTHNVIV KTEQTEPSIM NTWKDENYLY DTNYGSTVDL LDSKTFCRAQ ISMTTTSHLP 
VAESPDMKKE QDPPAKCHTK KHNPRGTHLW EFIRDILLNP DKNPGLIKWE DRSEGVFRFL 
KSEAVAQLWG KKKNNSSMTY EKLSRAMRYY YKREILERVD GRRLVYKFGK NARGWRENEN