Details for: TFF1

Gene ID: 7031

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: TFF1

Ensembl ID: ENSG00000160182

Description: trefoil factor 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • foveolar cell of stomach CL0002179
    CSI 29.57
    rCSI 62.94%
    PRS 91.53
  • BEST4+ enteroycte CL4030026
    CSI 15.16
    rCSI 18.86%
    PRS 88.8
  • paneth cell CL0000510
    CSI 14.71
    rCSI 21.72%
    PRS 94.5
  • intestinal epithelial cell CL0002563
    CSI 12.4
    rCSI 12.96%
    PRS 86.57
  • mucous neck cell CL0000651
    CSI 12.04
    rCSI 17.35%
    PRS 92.01
  • type EC enteroendocrine cell CL0000577
    CSI 9.16
    rCSI 32.51%
    PRS 90.41
  • small intestine goblet cell CL1000495
    CSI 8.63
    rCSI 18.89%
    PRS 91.73
  • transit amplifying cell CL0009010
    CSI 8.52
    rCSI 13.03%
    PRS 92.7
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 6.88
    rCSI 6.76%
    PRS 96.08
  • intestine goblet cell CL0019031
    CSI 6.47
    rCSI 5.74%
    PRS 86.39
  • mucus secreting cell CL0000319
    CSI 5.72
    rCSI 9.09%
    PRS 93.73
  • M cell of gut CL0000682
    CSI 5.62
    rCSI 5.97%
    PRS 91.35
  • IgA plasma cell CL0000987
    CSI 5.34
    rCSI 5.47%
    PRS 91.5
  • goblet cell CL0000160
    CSI 5.08
    rCSI 4.8%
    PRS 86.78
  • tracheal goblet cell CL1000329
    CSI 5.05
    rCSI 11.02%
    PRS 91.7
  • nasal mucosa goblet cell CL0002480
    CSI 4.91
    rCSI 5.7%
    PRS 89.79
  • secretory cell CL0000151
    CSI 4.85
    rCSI 5.06%
    PRS 87.92
  • epithelial cell CL0000066
    CSI 4.8
    rCSI 7.38%
    PRS 77.61
  • enteroendocrine cell CL0000164
    CSI 4.77
    rCSI 6.52%
    PRS 87.7
  • luminal cell of prostate epithelium CL0002340
    CSI 4.52
    rCSI 24.32%
    PRS 93.27
  • stem cell CL0000034
    CSI 3.98
    rCSI 3.84%
    PRS 84.51
  • luminal epithelial cell of mammary gland CL0002326
    CSI 3.87
    rCSI 7.02%
    PRS 94.32
  • natural T-regulatory cell CL0000903
    CSI 3.44
    rCSI 6.52%
    PRS 97.95
  • mononuclear phagocyte CL0000113
    CSI 3.24
    rCSI 7.14%
    PRS 91.49
  • colon epithelial cell CL0011108
    CSI 2.94
    rCSI 3.08%
    PRS 86.46
  • enteroendocrine cell of small intestine CL0009006
    CSI 2.88
    rCSI 6.34%
    PRS 92.43
  • pancreatic ductal cell CL0002079
    CSI 2.7
    rCSI 5.25%
    PRS 90.73
  • enteroendocrine cell of colon CL0009042
    CSI 2.53
    rCSI 11.85%
    PRS 91.84
  • IgG plasma cell CL0000985
    CSI 2.43
    rCSI 2.9%
    PRS 93.56
  • tracheobronchial serous cell CL0019001
    CSI 2.34
    rCSI 10.1%
    PRS 91.82
  • memory T cell CL0000813
    CSI 2.26
    rCSI 4.35%
    PRS 97.41
  • type L enteroendocrine cell CL0002279
    CSI 2.23
    rCSI 4.18%
    PRS 91.3
  • epithelial cell of lung CL0000082
    CSI 2.03
    rCSI 1.68%
    PRS 89.8
  • enterocyte CL0000584
    CSI 1.93
    rCSI 3.12%
    PRS 86.14
  • colonocyte CL1000347
    CSI 1.85
    rCSI 2.65%
    PRS 87.43
  • peptic cell CL0000155
    CSI 1.65
    rCSI 16.19%
    PRS 93.81
  • colon goblet cell CL0009039
    CSI 1.32
    rCSI 3.15%
    PRS 91.07
  • P/D1 enteroendocrine cell CL0002268
    CSI 1.29
    rCSI 7%
    PRS 91.85
  • bronchial goblet cell CL1000312
    CSI 0.87
    rCSI 3.49%
    PRS 92.46
  • parietal cell CL0000162
    CSI 0.67
    rCSI 5.79%
    PRS 94.27
  • respiratory goblet cell CL0002370
    CSI 0.64
    rCSI 6.99%
    PRS 92.45
  • epithelial cell of urethra CL1000296
    CSI 0.2
    rCSI 5.04%
    PRS 92.16

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 [TFF1](/details-gene/7031), or Trefoil Factor 1, is a secreted protein crucial for the maintenance and repair of mucosal surfaces, particularly within the gastrointestinal tract. Encoded on chromosome 21, it is a member of the trefoil factor family, a group of proteins characterized by a stable 'trefoil' domain structure. Expression data highlights its profound significance in specialized secretory epithelial cells of the stomach and intestines, such as [foveolar cell of stomach](/details-cell/CL0002179) and various [goblet cell](/details-cell/CL0000160) populations. Originally identified as an estrogen-responsive gene in breast cancer cell lines ([Link](https://doi.org/10.1093/nar/12.6.2861)), its function is now understood to be much broader, encompassing epithelial restitution, cytoprotection, and potential tumor suppression in the gastric environment. Clinically, alterations in [TFF1](/details-gene/7031) expression are associated with gastric cancer ([Link](https://doi.org/10.3748/wjg.v12.i19.3119)) and other gastrointestinal pathologies ([113710](https://omim.org/entry/113710)). ## Cellular Roles and Expression Landscape The expression profile of [TFF1](/details-gene/7031) underscores its specialized role as a key effector molecule in mucosal biology. **Overall**, the gene exhibits its highest significance in secretory epithelial cells lining the gastrointestinal tract. It is the top marker for [foveolar cell of stomach](/details-cell/CL0002179) (CSI: 29.57), the mucus-producing cells of the gastric pits, and is also highly significant in [mucous neck cell](/details-cell/CL0000651). This pattern extends throughout the intestines, with high significance in [BEST4+ enteroycte](/details-cell/CL4030026), [paneth cell](/details-cell/CL0000510), [small intestine goblet cell](/details-cell/CL1000495), and [intestine goblet cell](/details-cell/CL0019031). This widespread expression in mucus- and antimicrobial-secreting cells is consistent with its primary function in forming a protective barrier and promoting mucosal integrity. Beyond the major secretory lineages, [TFF1](/details-gene/7031) also shows relevance in progenitor cells, such as [transit amplifying cell](/details-cell/CL0009010), suggesting a role in epithelial differentiation and renewal. Interestingly, a notable signal is also observed in mucosal immune populations, including [activated CD8-positive, alpha-beta T cell](/details-cell/CL0000906) and [IgA plasma cell](/details-cell/CL0000987). This co-expression may point towards a secondary immunomodulatory function, where [TFF1](/details-gene/7031) mediates crosstalk between the epithelium and the local immune system to maintain homeostasis. ## Pathways and Molecular Function The functional annotations for [TFF1](/details-gene/7031) align closely with its cellular expression pattern, implicating it in epithelial defense, repair, and hormone-responsive signaling. * **Epithelial Maintenance and Proliferation:** The gene's involvement in [Maintenance of gastrointestinal epithelium (GO:0030277)](https://www.ebi.ac.uk/QuickGO/term/GO:0030277) is its most prominent annotated function, consistent with its high expression in gut lining cells. Its annotated [Growth factor activity (GO:0008083)](https://www.ebi.ac.uk/QuickGO/term/GO:0008083) and roles in both positive ([Cell population proliferation (GO:0008283)](https://www.ebi.ac.uk/QuickGO/term/GO:0008283)) and negative ([Negative regulation of cell population proliferation (GO:0008285)](https://www.ebi.ac.uk/QuickGO/term/GO:0008285)) regulation of cell growth suggest it plays a balanced role in tissue turnover and repair following injury. * **Hormonal Signaling:** Reactome pathways confirm its well-established link to estrogen signaling, including [Esr-mediated signaling (R-HSA-8939211)](https://reactome.org/content/detail/R-HSA-8939211) and [Estrogen-dependent gene expression (R-HSA-9018519)](https://reactome.org/content/detail/R-HSA-9018519). This connection was foundational to its discovery in breast cancer research ([Link](https://doi.org/10.1089/dna.1985.4.11)) and remains relevant in hormone-dependent malignancies. * **Secreted Factor:** As a secreted protein, its annotation to the [Extracellular region (GO:0005576)](https://www.ebi.ac.uk/QuickGO/term/GO:0005576) and [Extracellular space (GO:0005615)](https://www.ebi.ac.uk/QuickGO/term/GO:0005615) is consistent with its function as a component of the protective mucus layer, where it can interact with other proteins ([Protein binding (GO:0005515)](https://www.ebi.ac.uk/QuickGO/term/GO:0005515)) to stabilize the mucosal barrier. ## Research Directions The data solidifies the role of [TFF1](/details-gene/7031) as a cornerstone of gastrointestinal mucosal health, while also hinting at broader functions in immunomodulation and cancer biology. **Proposed Hypotheses:** 1. Given its role in epithelial maintenance and its high expression in gastric secretory cells, loss of [TFF1](/details-gene/7031) may be a critical early event in the pathogenesis of atrophic gastritis, increasing susceptibility to damage from agents like *H. pylori* or NSAIDs. 2. The observed significance of [TFF1](/details-gene/7031) in mucosal immune cells like [activated CD8-positive, alpha-beta T cell](/details-cell/CL0000906) and [IgA plasma cell](/details-cell/CL0000987) suggests a novel immunomodulatory role. We hypothesize that epithelial-derived [TFF1](/details-gene/7031) acts as a paracrine signal to temper inflammatory responses and support IgA production at the mucosal interface. **Key Experimental Approach:** To test the first hypothesis, a conditional knockout mouse model with a floxed *Tff1* allele could be crossed with a Foxa3-Cre line to specifically delete the gene in gastric and intestinal epithelial cells. These knockout mice and wild-type littermates would be challenged with chronic *H. pylori* infection. The resulting pathology would be assessed via histology for signs of atrophy and inflammation, quantitative PCR for inflammatory cytokine expression (e.g., *Il1b*, *Tnf*), and functional assays for gastric acid secretion and barrier permeability. A more severe disease phenotype in knockout mice would confirm the essential protective role of [TFF1](/details-gene/7031). **Therapeutic Potential:** [TFF1](/details-gene/7031) presents a compelling target for therapeutic activation or supplementation. Given its natural role in cytoprotection and wound healing, stable, orally-delivered recombinant [TFF1](/details-gene/7031) could be a viable therapeutic for conditions characterized by mucosal damage, such as inflammatory bowel disease, gastritis, and chemotherapy-induced mucositis. This approach would represent a pro-resolution and tissue-restorative strategy, aiming to augment the body's natural defense mechanisms rather than broadly suppressing inflammation.

Genular Protein ID: 1483583879

Symbol: TFF1_HUMAN

Name: Trefoil factor 1

UniProtKB Accession Codes:

P04155

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 DrugBank 2 EMBL 9 Ensembl 1 EvolutionaryTrace 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniLectin 1 VEuPathDB 1 eggNOG 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 6324130

Title: Sequence of the pS2 mRNA induced by estrogen in the human breast cancer cell line MCF-7.

PubMed ID: 6324130

DOI: 10.1093/nar/12.6.2861

PubMed ID: 3838275

Title: Cloning of a gene expressed in human breast cancer and regulated by estrogen in MCF-7 cells.

PubMed ID: 3838275

DOI: 10.1089/dna.1985.4.11

PubMed ID: 3822834

Title: Structure of the human oestrogen-responsive gene pS2.

PubMed ID: 3822834

DOI: 10.1093/nar/15.4.1401

PubMed ID: 2311759

Title: Expression of the pS2 gene in human gastric cancer cells derived from poorly differentiated adenocarcinoma.

PubMed ID: 2311759

DOI: 10.1016/0014-5793(90)80572-z

PubMed ID: 2185238

Title: Complete primary structure of the human estrogen-responsive gene (pS2) product.

PubMed ID: 2185238

DOI: 10.1093/oxfordjournals.jbchem.a123014

PubMed ID: 10950923

Title: Refined localization of autosomal recessive nonsyndromic deafness DFNB10 locus using 34 novel microsatellite markers, genomic structure, and exclusion of six known genes in the region.

PubMed ID: 10950923

DOI: 10.1006/geno.2000.6253

PubMed ID: 10830953

Title: The DNA sequence of human chromosome 21.

PubMed ID: 10830953

DOI: 10.1038/35012518

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: 3146413

Title: Primary structure of human protein pS2.

PubMed ID: 3146413

PubMed ID: 15924415

Title: Interaction between TFF1, a gastric tumor suppressor trefoil protein, and TFIZ1, a Brichos domain-containing protein with homology to SP-C.

PubMed ID: 15924415

DOI: 10.1021/bi047287n

PubMed ID: 16308573

Title: Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor.

PubMed ID: 16308573

DOI: 10.1172/jci25342

PubMed ID: 3261981

Title: Identification of a polypeptide secreted by human breast cancer cells (MCF-7) as the human estrogen-responsive gene (pS2) product.

PubMed ID: 3261981

DOI: 10.1016/s0006-291x(88)81094-5

PubMed ID: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 3041593

Title: Breast cancer-associated pS2 protein: synthesis and secretion by normal stomach mucosa.

PubMed ID: 3041593

DOI: 10.1126/science.3041593

PubMed ID: 16718800

Title: Expression of trefoil factors 1 and 2 in precancerous condition and gastric cancer.

PubMed ID: 16718800

DOI: 10.3748/wjg.v12.i19.3119

PubMed ID: 17143957

Title: Molecular forms of trefoil factor 1 in normal gastric mucosa and its expression in normal and abnormal gastric tissues.

PubMed ID: 17143957

DOI: 10.3748/wjg.v12.i45.7361

PubMed ID: 17242463

Title: Tissue localization of human trefoil factors 1, 2, and 3.

PubMed ID: 17242463

DOI: 10.1369/jhc.6a7100.2007

PubMed ID: 8521850

Title: NMR-based structural studies of the pNR-2/pS2 single domain trefoil peptide. Similarities to porcine spasmolytic peptide and evidence for a monomeric structure.

PubMed ID: 8521850

DOI: 10.1111/j.1432-1033.1995.847_3.x

PubMed ID: 9096235

Title: High-resolution solution structure of human pNR-2/pS2: a single trefoil motif protein.

PubMed ID: 9096235

DOI: 10.1006/jmbi.1997.0896

PubMed ID: 10982763

Title: Somatic mutations of the trefoil factor family 1 gene in gastric cancer.

PubMed ID: 10982763

DOI: 10.1053/gast.2000.16483

PubMed ID: 16697734

Title: Trefoil factor family-1 mutations enhance gastric cancer cell invasion through distinct signaling pathways.

PubMed ID: 16697734

DOI: 10.1053/j.gastro.2006.01.040

Sequence Information:

  • Length: 84
  • Mass: 9150
  • Checksum: 65198523BAD6EBC7
  • Sequence:
    • MATMENKVIC ALVLVSMLAL GTLAEAQTET CTVAPRERQN CGFPGVTPSQ CANKGCCFDD 
TVRGVPWCFY PNTIDVPPEE ECEF