Details for: SECTM1

Gene ID: 6398

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: SECTM1

Ensembl ID: ENSG00000141574

Description: secreted and transmembrane 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • goblet cell CL0000160
    CSI 19.03
    rCSI 17.98%
    PRS 95.97
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 12.48
    rCSI 9.61%
    PRS 98.48
  • colon epithelial cell CL0011108
    CSI 9.11
    rCSI 9.54%
    PRS 96.07
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 6.65
    rCSI 8.72%
    PRS 99.17
  • enterocyte CL0000584
    CSI 6.11
    rCSI 9.85%
    PRS 94.93
  • neutrophil CL0000775
    CSI 5.39
    rCSI 30.14%
    PRS 94.68
  • alternatively activated macrophage CL0000890
    CSI 5.29
    rCSI 6.65%
    PRS 99.21
  • BEST4+ enteroycte CL4030026
    CSI 4.96
    rCSI 6.17%
    PRS 96.48
  • colonocyte CL1000347
    CSI 4.78
    rCSI 6.85%
    PRS 96
  • intestine goblet cell CL0019031
    CSI 4.13
    rCSI 3.66%
    PRS 95.98
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.68
    rCSI 3.54%
    PRS 96.34
  • myeloid leukocyte CL0000766
    CSI 3.16
    rCSI 2.92%
    PRS 97.96
  • elicited macrophage CL0000861
    CSI 3.14
    rCSI 2.88%
    PRS 98.79
  • nasal mucosa goblet cell CL0002480
    CSI 3.11
    rCSI 3.61%
    PRS 96.51
  • lung macrophage CL1001603
    CSI 2.9
    rCSI 6.48%
    PRS 98.87
  • mononuclear phagocyte CL0000113
    CSI 2.34
    rCSI 5.15%
    PRS 98.18
  • foveolar cell of stomach CL0002179
    CSI 2.01
    rCSI 4.27%
    PRS 97.43
  • alveolar macrophage CL0000583
    CSI 1.98
    rCSI 3.26%
    PRS 97.54
  • basal cell of epidermis CL0002187
    CSI 1.8
    rCSI 3.19%
    PRS 77.16
  • intermediate monocyte CL0002393
    CSI 1.56
    rCSI 2.35%
    PRS 98.78
  • mammary gland epithelial cell CL0002327
    CSI 1.35
    rCSI 4.73%
    PRS 98.6
  • melanocyte of skin CL1000458
    CSI 1.18
    rCSI 1.61%
    PRS 78.05
  • CD14-positive, CD16-negative classical monocyte CL0002057
    CSI 0.72
    rCSI 4.35%
    PRS 98.86

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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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 [SECTM1](/details-gene/6398) (Secreted and Transmembrane Protein 1) is a protein-coding gene located on chromosome 17q25.3. It encodes a type I transmembrane protein that can also exist in a secreted form and is associated with the Golgi apparatus ([Link](https://doi.org/10.1006/geno.1997.5151)). Functionally, [SECTM1](/details-gene/6398) is implicated in the [immune response](/details-go/GO:0006955) and signal transduction, acting as a ligand with [cytokine activity](/details-go/GO:0005125). Expression data highlights its significant role in both mucosal epithelial cells, such as [goblet cell](/details-cell/CL0000160)s, and myeloid-lineage immune cells, including [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s, suggesting a key function at the interface between barrier tissues and the immune system. It has been identified as a ligand for the T-cell co-receptor CD7, indicating a role in modulating T-cell activity ([Link](https://doi.org/10.1074/jbc.275.5.3431)). ## Cellular Roles and Expression Landscape The expression profile of [SECTM1](/details-gene/6398) reveals a distinct pattern of significance in two primary cellular compartments: mucosal epithelia and myeloid cells. **Overall**, the gene shows the highest significance in secretory epithelial cells of the gastrointestinal tract, including [goblet cell](/details-cell/CL0000160) (CSI: 19.03), [colon epithelial cell](/details-cell/CL0011108) (CSI: 9.11), and [enterocyte](/details-cell/CL0000584) (CSI: 6.11). This strong association with intestinal barrier cells suggests a role in mucosal homeostasis and host defense. Concurrently, [SECTM1](/details-gene/6398) is a highly significant gene in several myeloid populations. It is prominently expressed in [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s (CSI: 12.48), also known as non-classical monocytes, as well as in [neutrophil](/details-cell/CL0000775)s (CSI: 5.39) and various macrophage subtypes like [alternatively activated macrophage](/details-cell/CL0000890)s (CSI: 5.29). This expression pattern points towards its involvement in innate immune surveillance and the regulation of subsequent adaptive immune responses, particularly through its established interaction with CD7 on T-lymphocytes ([Link](https://doi.org/10.1074/jbc.275.5.3431)). The expression in thymic epithelial cells and its regulation by IFN-gamma further solidifies its role in T-cell biology ([Link](https://doi.org/10.1007/s10875-005-0356-5)). ## Pathways and Molecular Function The functional annotations for [SECTM1](/details-gene/6398) are highly consistent with its observed cellular expression pattern. Its role as a secreted or membrane-bound protein is supported by its localization to the [extracellular space](/details-go/GO:0005615), [extracellular exosome](/details-go/GO:0070062), and the [plasma membrane](/details-go/GO:0005886). Biologically, [SECTM1](/details-gene/6398) is primarily associated with the [immune response](/details-go/GO:0006955). Its molecular functions as a [receptor ligand](/details-go/GO:0048018) and possessing [cytokine activity](/details-go/GO:0005125) directly explain its ability to influence immune cell behavior. This is further specified by its involvement in the [positive regulation of t cell cytokine production](/details-go/GO:0002726), a process directly linked to its function as a ligand for CD7 expressed on T cells. This interaction likely underpins its involvement in broader [signal transduction](/details-go/GO:0007165) pathways, potentially including the [positive regulation of canonical nf-kappab signal transduction](/details-go/GO:0043123), which is a central pathway in inflammation and immunity. ## Research Directions The dual expression pattern of [SECTM1](/details-gene/6398) in both mucosal barrier cells and professional antigen-presenting cells provides a foundation for several compelling research avenues. ### Proposed Hypotheses: 1. **Hypothesis 1:** Secreted [SECTM1](/details-gene/6398) from intestinal epithelial cells, such as [goblet cell](/details-cell/CL0000160)s, acts as a paracrine signal to modulate the function of local immune cells in the gut lamina propria, thereby contributing to the maintenance of mucosal tolerance or the initiation of inflammatory responses in the context of disease (e.g., Inflammatory Bowel Disease). 2. **Hypothesis 2:** Membrane-bound [SECTM1](/details-gene/6398) on myeloid cells, particularly [CD14-low, CD16-positive monocyte](/details-cell/CL0002396)s and macrophages, functions as a critical co-stimulatory ligand for CD7+ T cells, polarizing T cell differentiation and cytokine production during an active immune response. ### Experimental Approach: To test Hypothesis 2, a co-culture system could be employed. Primary human [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397)s could be isolated and differentiated into macrophages in vitro. [SECTM1](/details-gene/6398) expression would be knocked down using shRNA or CRISPR-Cas9 gene editing in one cohort of these cells. These SECTM1-deficient macrophages, along with control macrophages, would then be co-cultured with purified autologous CD7+ T cells in the presence of a sub-optimal T-cell receptor stimulus (e.g., anti-CD3 antibody). The impact of [SECTM1](/details-gene/6398) expression on T cell activation could be quantified by measuring T cell proliferation (via CFSE dilution by flow cytometry) and the secretion of key cytokines like IFN-γ and IL-17 (via ELISA or multiplex bead array). A significant reduction in T-cell proliferation and cytokine production in the absence of [SECTM1](/details-gene/6398) would support its role as a co-stimulatory molecule. ### Therapeutic Potential: Given its role as an extracellular ligand that modulates T cell activity, [SECTM1](/details-gene/6398) presents a plausible therapeutic target. In autoimmune or chronic inflammatory diseases characterized by excessive T cell activation, such as rheumatoid arthritis or IBD, blocking the SECTM1-CD7 interaction could be a viable strategy. Therefore, development of a monoclonal antibody or small molecule to inhibit this interaction represents a potential therapeutic avenue. The strategy would focus on **inhibition** to dampen pathogenic immune responses. Its specificity to certain myeloid and epithelial subsets could potentially offer a more targeted immunomodulatory approach compared to broader-acting immunosuppressants.

Genular Protein ID: 4243587082

Symbol: SCTM1_HUMAN

Name: Secreted and transmembrane protein 1

UniProtKB Accession Codes:

Q8WVN6 B2R7H0 O00466

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 1 ExpressionAtlas 1 GO 11 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 RefSeq 3 SMR 1 STRING 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9480746

Title: Identification and characterization of K12 (SECTM1), a novel human gene that encodes a Golgi-associated protein with transmembrane and secreted isoforms.

PubMed ID: 9480746

DOI: 10.1006/geno.1997.5151

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: 10652336

Title: Identification of CD7 as a cognate of the human K12 (SECTM1) protein.

PubMed ID: 10652336

DOI: 10.1074/jbc.275.5.3431

PubMed ID: 15742156

Title: Expression of the CD7 ligand K-12 in human thymic epithelial cells: regulation by IFN-gamma.

PubMed ID: 15742156

DOI: 10.1007/s10875-005-0356-5

Sequence Information:

  • Length: 248
  • Mass: 27039
  • Checksum: 21E3066B67920487
  • Sequence:
    • MQTCPLAFPG HVSQALGTLL FLAASLSAQN EGWDSPICTE GVVSVSWGEN TVMSCNISNA 
FSHVNIKLRA HGQESAIFNE VAPGYFSRDG WQLQVQGGVA QLVIKGARDS HAGLYMWHLV 
GHQRNNRQVT LEVSGAEPQS APDTGFWPVP AVVTAVFILL VALVMFAWYR CRCSQQRREK 
KFFLLEPQMK VAALRAGAQQ GLSRASAELW TPDSEPTPRP LALVFKPSPL GALELLSPQP 
LFPYAADP