Details for: SCGB1A1

Gene ID: 7356

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: SCGB1A1

Ensembl ID: ENSG00000149021

Description: secretoglobin family 1A member 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • epithelial cell of lower respiratory tract CL0002632
    CSI 132.73
    rCSI 100%
    PRS 5.38
  • club cell CL0000158
    CSI 75.45
    rCSI 100%
    PRS 6.67
  • multi-ciliated epithelial cell CL0005012
    CSI 63.74
    rCSI 63.61%
    PRS 4.84
  • nasal mucosa goblet cell CL0002480
    CSI 61.88
    rCSI 71.77%
    PRS 8.4
  • goblet cell CL0000160
    CSI 59.25
    rCSI 55.98%
    PRS 5.9
  • respiratory suprabasal cell CL4033048
    CSI 55.82
    rCSI 71.58%
    PRS 6.53
  • secretory cell CL0000151
    CSI 53.2
    rCSI 55.51%
    PRS 5.78
  • tracheal goblet cell CL1000329
    CSI 38.93
    rCSI 85%
    PRS 11.53
  • respiratory basal cell CL0002633
    CSI 33.81
    rCSI 35.02%
    PRS 6.63
  • bronchial goblet cell CL1000312
    CSI 27.75
    rCSI 100%
    PRS 12.55
  • deuterosomal cell CL4033044
    CSI 26.76
    rCSI 90.45%
    PRS 9.69
  • lung secretory cell CL1000272
    CSI 24.83
    rCSI 61.46%
    PRS 5.23
  • lung ciliated cell CL1000271
    CSI 23.21
    rCSI 26.84%
    PRS 4.12
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 21.14
    rCSI 48.18%
    PRS 5.91
  • duct epithelial cell CL0000068
    CSI 19.62
    rCSI 28.7%
    PRS 5.98
  • epithelial cell of lung CL0000082
    CSI 19.4
    rCSI 16.08%
    PRS 5.35
  • tracheobronchial serous cell CL0019001
    CSI 15.94
    rCSI 68.87%
    PRS 11.02
  • ciliated epithelial cell CL0000067
    CSI 14.48
    rCSI 12.73%
    PRS 4.08
  • pulmonary ionocyte CL0017000
    CSI 11.89
    rCSI 14.48%
    PRS 7.15
  • ciliated cell CL0000064
    CSI 10.85
    rCSI 17.58%
    PRS 5.74
  • brush cell of tracheobronchial tree CL0002075
    CSI 10.75
    rCSI 31.91%
    PRS 9.38
  • lung goblet cell CL1000143
    CSI 9.92
    rCSI 100%
    PRS 20.25
  • respiratory goblet cell CL0002370
    CSI 8.03
    rCSI 87.33%
    PRS 10.69
  • mucus secreting cell CL0000319
    CSI 7.98
    rCSI 12.67%
    PRS 7.36
  • basal cell of epithelium of trachea CL1000348
    CSI 7.72
    rCSI 54.51%
    PRS 18.38
  • pulmonary capillary endothelial cell CL4028001
    CSI 7.42
    rCSI 14.15%
    PRS 9.1
  • Langerhans cell CL0000453
    CSI 7.38
    rCSI 11.28%
    PRS 9.93
  • glutamatergic neuron CL0000679
    CSI 6.45
    rCSI 13.25%
    PRS 6.24
  • acinar cell CL0000622
    CSI 6.44
    rCSI 9.45%
    PRS 7.42
  • pulmonary artery endothelial cell CL1001568
    CSI 6.43
    rCSI 8.74%
    PRS 8.7
  • bronchus fibroblast of lung CL2000093
    CSI 6.26
    rCSI 5.08%
    PRS 6.01
  • tracheobronchial goblet cell CL0019003
    CSI 6.17
    rCSI 99.1%
    PRS 69.23
  • fibroblast of lung CL0002553
    CSI 5.38
    rCSI 5.01%
    PRS 5.7
  • neutrophil CL0000775
    CSI 5.11
    rCSI 28.61%
    PRS 16.93
  • vein endothelial cell of respiratory system CL4033008
    CSI 5.02
    rCSI 34.44%
    PRS 11.3
  • chondrocyte CL0000138
    CSI 4.23
    rCSI 6.72%
    PRS 5.1
  • lung neuroendocrine cell CL1000223
    CSI 4.2
    rCSI 6.21%
    PRS 6.5
  • pulmonary alveolar type 2 cell CL0002063
    CSI 4.02
    rCSI 6.24%
    PRS 8.91
  • airway submucosal gland duct basal cell CL4033024
    CSI 3.75
    rCSI 23.96%
    PRS 24.5
  • blood vessel endothelial cell CL0000071
    CSI 3.69
    rCSI 7.66%
    PRS 5.63
  • dendritic cell CL0000451
    CSI 3.54
    rCSI 4.36%
    PRS 19.09
  • squamous epithelial cell CL0000076
    CSI 3.4
    rCSI 8.06%
    PRS 7.52
  • ionocyte CL0005006
    CSI 3.17
    rCSI 3.4%
    PRS 5.21
  • mast cell CL0000097
    CSI 2.99
    rCSI 6.46%
    PRS 31.92
  • adventitial cell CL0002503
    CSI 2.78
    rCSI 6.64%
    PRS 9.16
  • respiratory hillock cell CL4030023
    CSI 2.74
    rCSI 4.89%
    PRS 9.8
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 2.54
    rCSI 3.07%
    PRS 6.63
  • epithelial cell of urethra CL1000296
    CSI 2.53
    rCSI 63.63%
    PRS 19.99
  • IgG plasma cell CL0000985
    CSI 2.17
    rCSI 2.6%
    PRS 9.83
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.06
    rCSI 2.25%
    PRS 6.57
  • vein endothelial cell CL0002543
    CSI 1.91
    rCSI 5.21%
    PRS 25.29
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.68
    rCSI 4.83%
    PRS 8.18
  • lung pericyte CL0009089
    CSI 1.62
    rCSI 4.28%
    PRS 6.77
  • pulmonary alveolar type 1 cell CL0002062
    CSI 1.32
    rCSI 7.62%
    PRS 8.32
  • myeloid dendritic cell, human CL0001057
    CSI 1.14
    rCSI 6.41%
    PRS 18.43
  • lung resident memory CD8-positive, alpha-beta T cell CL4033039
    CSI 0.95
    rCSI 2.45%
    PRS 19.11
  • lung macrophage CL1001603
    CSI 0.24
    rCSI 0.53%
    PRS 6.4
  • alveolar macrophage CL0000583
    CSI 0.15
    rCSI 0.25%
    PRS 6.63
  • tracheobronchial smooth muscle cell CL0019019
    CSI -8.91
    rCSI -15.71%
    PRS 7.52
  • alveolar adventitial fibroblast CL4028006
    CSI -14.03
    rCSI -22.16%
    PRS 5.68
  • elicited macrophage CL0000861
    CSI -29.98
    rCSI -27.53%
    PRS 6.46

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.

Comma-separated if multiple.
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 [SCGB1A1](/details-gene/7356), or secretoglobin family 1A member 1, is a protein-coding gene located on chromosome 11q12.3. Also widely known as Uteroglobin or Clara cell 10-kDa protein (CC10), it is a small, secreted protein with potent immunomodulatory and anti-inflammatory properties. Functionally, it is characterized by its ability to inhibit phospholipase A2 and negatively regulate the production of key cytokines involved in type 2 immune responses, such as IL-4, IL-5, and IL-13. Expression data reveal that [SCGB1A1](/details-gene/7356) is a dominant and highly specific marker for secretory cells of the respiratory tract, most notably `[epithelial cell of lower respiratory tract](/details-cell/CL0002632)` and `[club cell](/details-cell/CL0000158)`, suggesting a critical role in maintaining homeostasis and protecting the lung environment. Its clinical relevance is noted under OMIM entry [192020](https://omim.org/entry/192020). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [SCGB1A1](/details-gene/7356) establishes it as a cornerstone gene for the identity and function of the airway epithelium. The gene demonstrates exceptionally high significance in `[epithelial cell of lower respiratory tract](/details-cell/CL0002632)` (CSI: 132.73), followed by more specialized secretory cell types including `[club cell](/details-cell/CL0000158)` (CSI: 75.45) and various `[goblet cell](/details-cell/CL0000160)` populations. This strong and specific expression pattern across multiple secretory and ciliated cell types, such as `[multi-ciliated epithelial cell](/details-cell/CL0005012)` and `[lung ciliated cell](/details-cell/CL1000271)`, underscores its integral role in producing the protective lining of the respiratory system. The gene's specificity is further highlighted by its notable lack of expression in other cell lineages within the lung microenvironment. For instance, it serves as a strong anti-marker for `[elicited macrophage](/details-cell/CL0000861)` (CSI: -29.98) and structural cells like `[alveolar adventitial fibroblast](/details-cell/CL4028006)` and `[tracheobronchial smooth muscle cell](/details-cell/CL0019019)`. This highly restricted expression pattern suggests that its functions are primarily executed by the epithelial barrier, acting upon both the epithelial cells themselves and adjacent immune cells. ## Pathways and Molecular Function The molecular functions of [SCGB1A1](/details-gene/7356) are strongly linked to inflammation control and host defense, consistent with its secretion into the airway lumen. A primary annotated function is `[phospholipase A2 inhibitor activity](/details-link/GO:0019834)`, a key mechanism for dampening the production of pro-inflammatory lipid mediators like prostaglandins and leukotrienes. This anti-inflammatory capacity is further detailed by its involvement in multiple immunomodulatory processes. [SCGB1A1](/details-gene/7356) is implicated in the `[negative regulation of interleukin-4 production](/details-link/GO:0032713)`, `[negative regulation of interleukin-5 production](/details-link/GO:0032714)`, and `[negative regulation of interleukin-13 production](/details-link/GO:0032696)`. These annotations position it as a key suppressor of Th2-mediated inflammation, which is central to allergic diseases like asthma. Furthermore, its role in the `[negative regulation of t cell proliferation](/details-link/GO:0042130)` suggests a broader capacity to control adaptive immune responses. Beyond its role in the respiratory system, its original name, Uteroglobin, reflects its involvement in reproductive processes such as `[embryo implantation](/details-link/GO:0007566)` and `[female pregnancy](/details-link/GO:0007565)`, as initially described in rabbit models ([Link](https://pubmed.ncbi.nlm.nih.gov/1284526/)). As a secreted protein found in the `[extracellular space](/details-link/GO:0005615)` and `[secretory granule](/details-link/GO:0030141)`, it is well-positioned to respond to a wide array of environmental challenges, including `[response to lipopolysaccharide](/details-link/GO:0032496)` and `[response to xenobiotic stimulus](/details-link/GO:0009410)`. ## Research Directions Based on its well-defined role as a secreted, anti-inflammatory protein highly specific to the airway epithelium, several research avenues emerge. **Proposed Hypotheses:** 1. Given its potent negative regulation of Th2 cytokines, the loss of [SCGB1A1](/details-gene/7356) function in `[club cell](/details-cell/CL0000158)s` is a critical factor in the pathogenesis of allergic asthma, leading to an exaggerated inflammatory response to common allergens. 2. Considering its role in responding to external stimuli, [SCGB1A1](/details-gene/7356) acts as a "molecular sponge" in the airway surface liquid, binding and neutralizing inhaled pollutants and irritants, and its depletion may increase susceptibility to environmentally-induced lung injury. **Experimental Approach:** To test the first hypothesis, a conditional knockout mouse model could be employed. Specifically, deleting *Scgb1a1* in club cells using a Cre-Lox system (e.g., *Scgb1a1*-CreERT2 mice) would allow for cell-type-specific investigation. These mice, alongside wild-type controls, would be subjected to a classic model of allergic airway inflammation, such as ovalbumin or house dust mite (HDM) sensitization and challenge. Key readouts would include quantification of eosinophils and lymphocytes in bronchoalveolar lavage fluid (BALF), measurement of IL-4, IL-5, and IL-13 levels in BALF and lung tissue homogenates via ELISA, and assessment of airway hyperresponsiveness using plethysmography. A significantly more severe inflammatory phenotype in the knockout mice would validate the protective role of club cell-derived SCGB1A1 in asthma. **Therapeutic Potential:** The biological properties of [SCGB1A1](/details-gene/7356) make it an attractive candidate for therapeutic development. As a secreted protein with powerful, localized anti-inflammatory effects, it is well-suited for protein replacement or supplementation strategies, rather than inhibition. The development of a recombinant human SCGB1A1, delivered directly to the lungs via nebulization, could serve as a novel biologic therapy for inflammatory airway diseases such as severe asthma, chronic obstructive pulmonary disease (COPD), or acute respiratory distress syndrome (ARDS). Its high specificity for the respiratory tract suggests that such a therapy could offer potent local efficacy with a reduced risk of systemic side effects.

Genular Protein ID: 871660389

Symbol: UTER_HUMAN

Name: Uteroglobin

UniProtKB Accession Codes:

P11684 B2R5F2 Q6FHH3 Q9UCM2 Q9UCM4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 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 1 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 26 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 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 2 PDBsum 2 PIR 2 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3167058

Title: Amino-acid and cDNA nucleotide sequences of human Clara cell 10 kDa protein.

PubMed ID: 3167058

DOI: 10.1016/0167-4781(88)90129-7

PubMed ID: 7733299

Title: Human CC10 gene expression in airway epithelium and subchromosomal locus suggest linkage to airway disease.

PubMed ID: 7733299

DOI: 10.1152/ajplung.1995.268.4.l565

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 1284526

Title: Human CC10, the homologue of rabbit uteroglobin: genomic cloning, chromosomal localization and expression in endometrial cell lines.

PubMed ID: 1284526

DOI: 10.1093/hmg/1.6.371

PubMed ID: 1400743

Title: Simple and high-yield purification of urine protein 1 using immunoaffinity chromatography: evidence for the identity of urine protein 1 and human Clara cell 10-kilodalton protein.

PubMed ID: 1400743

DOI: 10.1016/0378-4347(92)80595-h

PubMed ID: 1395029

Title: Human urinary protein 1: evidence for identity with the Clara cell protein and occurrence in respiratory tract and urogenital secretions.

PubMed ID: 1395029

DOI: 10.1016/0009-8981(92)90122-7

PubMed ID: 11788998

Title: Newly identified proteins in human nasal lavage fluid from non-smokers and smokers using two-dimensional gel electrophoresis and peptide mass fingerprinting.

PubMed ID: 11788998

DOI: 10.1002/1615-9861(200201)2:1<112::aid-prot112>3.3.co;2-e

PubMed ID: 16423471

Title: Interaction of uteroglobin with lipocalin-1 receptor suppresses cancer cell motility and invasion.

PubMed ID: 16423471

DOI: 10.1016/j.gene.2005.10.027

PubMed ID: 23964685

Title: Expression, characterization and ligand specificity of lipocalin-1 interacting membrane receptor (LIMR).

PubMed ID: 23964685

DOI: 10.3109/09687688.2013.823018

PubMed ID: 7664082

Title: Structure of a human Clara cell phospholipid-binding protein-ligand complex at 1.9-A resolution.

PubMed ID: 7664082

DOI: 10.1038/nsb0894-538

Sequence Information:

  • Length: 91
  • Mass: 9994
  • Checksum: FE65ACA678F12ABD
  • Sequence:
    • MKLAVTLTLV TLALCCSSAS AEICPSFQRV IETLLMDTPS SYEAAMELFS PDQDMREAGA 
QLKKLVDTLP QKPRESIIKL MEKIAQSSLC N