Details for: B3GNT6

Gene ID: 192134

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: B3GNT6

Ensembl ID: ENSG00000198488

Description: UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6

Cell Significance Landscape

Associated with

  • Metabolism of proteins
    (R-HSA-392499)
  • O-linked glycosylation
    (R-HSA-5173105)
  • O-linked glycosylation of mucins
    (R-HSA-913709)
  • Post-translational protein modification
    (R-HSA-597592)
  • Acetylgalactosaminyl-o-glycosyl-glycoprotein beta-1,3-n-acetylglucosaminyltransferase activity
    (GO:0047224)
  • Beta-1,3-galactosyl-o-glycosyl-glycoprotein beta-1,3-n-acetylglucosaminyltransferase activity
    (GO:0047223)
  • Galactosyltransferase activity
    (GO:0008378)
  • Glycoprotein biosynthetic process
    (GO:0009101)
  • Golgi membrane
    (GO:0000139)
  • Membrane
    (GO:0016020)
  • O-glycan processing
    (GO:0016266)
  • O-glycan processing, core 3
    (GO:0016269)
  • Poly-n-acetyllactosamine biosynthetic process
    (GO:0030311)
  • Protein o-linked glycosylation
    (GO:0006493)
  • Udp-galactose:beta-n-acetylglucosamine beta-1,3-galactosyltransferase activity
    (GO:0008499)
  • Udp-glycosyltransferase activity
    (GO:0008194)

Significant Cells

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

  • colon goblet cell CL0009039
    CSI 6.78
    rCSI 16.12%
    PRS 99.44
  • intestine goblet cell CL0019031
    CSI 6.73
    rCSI 5.97%
    PRS 99.1
  • goblet cell CL0000160
    CSI 5.22
    rCSI 4.93%
    PRS 99.24
  • lung secretory cell CL1000272
    CSI 3.83
    rCSI 9.48%
    PRS 99.75
  • small intestine goblet cell CL1000495
    CSI 3.7
    rCSI 8.1%
    PRS 99.58
  • mucus secreting cell CL0000319
    CSI 3.44
    rCSI 5.47%
    PRS 99.74

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 [B3GNT6](/details-gene/192134) (beta-1,3-N-acetylglucosaminyltransferase 6) is a protein-coding gene located on chromosome 11q13.5. It encodes a glycosyltransferase enzyme critical for the synthesis of O-glycans, specifically the formation of the core 3 structure (GlcNAcβ1-3GalNAcα1-Ser/Thr) [Link](https://doi.org/10.1074/jbc.m112457200). Expression data indicates that [B3GNT6](/details-gene/192134) is a highly specific and abundant marker for mucus-producing cells, with its highest significance observed in [colon goblet cells](/details-cell/CL0009039) and other secretory cell types of the gastrointestinal and respiratory tracts. Its function is integral to the process of O-linked glycosylation, which is essential for the proper structure and function of mucins, the primary protein components of mucus. ## Cellular Roles and Expression Landscape The expression profile of [B3GNT6](/details-gene/192134) points to a highly specialized role in mucosal biology. **Overall**, the gene demonstrates its highest significance in secretory epithelial lineages responsible for producing protective mucus layers. * **Primary Expression Context:** The gene is most significant in [colon goblet cell](/details-cell/CL0009039) (CSI: 6.78), [intestine goblet cell](/details-cell/CL0019031) (CSI: 6.73), and the broader [goblet cell](/details-cell/CL0000160) category (CSI: 5.22). Its prominence extends to [lung secretory cell](/details-cell/CL1000272) (CSI: 3.83) and [mucus secreting cell](/details-cell/CL0000319) (CSI: 3.44). This restricted and high-level expression pattern establishes [B3GNT6](/details-gene/192134) as a key enzymatic workhorse for O-glycan synthesis in tissues that require a mucus barrier. The synthesis of core 3 O-glycans by [B3GNT6](/details-gene/192134) is a critical step in the production of normal mucins in the colon and other mucosal surfaces. ## Pathways and Molecular Function The functional annotations for [B3GNT6](/details-gene/192134) are highly consistent with its observed expression pattern in secretory cells. The gene product is localized to the [Golgi membrane](/details-cell/GO:0000139), the primary site for protein glycosylation. * **Biological Processes:** [B3GNT6](/details-gene/192134) is centrally involved in [O-glycan processing](/details-cell/GO:0016266), and more specifically, the synthesis of the core 3 structure ([O-glycan processing, core 3](/details-cell/GO:0016269)). This activity is part of the broader processes of [glycoprotein biosynthetic process](/details-cell/GO:0009101) and [protein o-linked glycosylation](/details-cell/GO:0006493). * **Molecular Function:** Its enzymatic role is defined as 'acetylgalactosaminyl-o-glycosyl-glycoprotein beta-1,3-n-acetylglucosaminyltransferase activity' ([GO:0047224](https://www.ebi.ac.uk/QuickGO/term/GO:0047224)). This function is integral to pathways such as [O-linked glycosylation of mucins](/details-pathway/R-HSA-913709) and the more general [Metabolism of proteins](/details-pathway/R-HSA-392499) and [Post-translational protein modification](/details-pathway/R-HSA-597592) pathways. ## Research Directions Research suggests that the role of [B3GNT6](/details-gene/192134) extends beyond normal mucosal physiology and into cancer biology. Published studies indicate that the activity of this core 3 synthase is often lost in colon cancer cell lines [Link](https://doi.org/10.1093/glycob/5.3.351), and its expression is significantly down-regulated in colon carcinoma. This loss has been shown to profoundly suppress the metastatic potential of carcinoma cells, suggesting a tumor-suppressive function [Link](https://doi.org/10.1073/pnas.0407983102). This highlights a critical axis for future investigation into the mechanisms linking altered glycosylation to cancer progression. **Proposed Hypotheses:** 1. The loss of [B3GNT6](/details-gene/192134) expression in colorectal cancer leads to a shift from core 3-derived O-glycans to truncated, oncofetal O-glycans (e.g., Tn and sialyl-Tn antigens). This altered "glycocalyx" disrupts normal cell-cell adhesion mediated by mucins and promotes signaling pathways associated with metastasis. 2. Epigenetic silencing, such as DNA hypermethylation of the [B3GNT6](/details-gene/192134) promoter or regulation by specific microRNAs, is a primary mechanism for its down-regulation during the progression from normal colonic epithelium to adenocarcinoma. **Experimental Approach:** To test hypothesis 1, a compelling experiment would involve the stable re-expression of [B3GNT6](/details-gene/192134) in a human colon cancer cell line known to lack its expression. The functional consequences could be assessed by: * **Glycoproteomic Analysis:** Using mass spectrometry to confirm the restoration of core 3 O-glycans on cell surface and secreted glycoproteins. * **Functional Assays:** Performing in vitro cell adhesion, migration, and invasion assays (e.g., using a transwell system) to determine if re-expression of [B3GNT6](/details-gene/192134) and restoration of core 3 glycans reduces the malignant phenotype. * **In Vivo Modeling:** Utilizing a xenograft mouse model to assess if [B3GNT6](/details-gene/192134) re-expression can suppress tumor growth and metastasis in vivo. **Therapeutic Potential:** Given that the loss of [B3GNT6](/details-gene/192134) is associated with cancer progression, it is not a candidate for therapeutic inhibition. Instead, it represents a potential tumor suppressor. Therapeutic strategies could focus on its **activation** or restoration. If its loss is due to epigenetic silencing, drugs that inhibit DNA methylation (e.g., decitabine) or histone deacetylation could potentially restore its expression. Furthermore, the expression level of [B3GNT6](/details-gene/192134) in colorectal tumor biopsies could serve as a valuable prognostic biomarker to predict metastatic risk and guide patient treatment strategies.

Genular Protein ID: 4190962901

Symbol: B3GN6_HUMAN

Name: Acetylgalactosaminyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase

UniProtKB Accession Codes:

Q6ZMB0 E9PKS1 Q6ZSC5 Q8TAZ4 Q8TDX1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CAZy 1 CCDS 1 CTD 1 ChEBI 10 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 1 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 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 1 Rhea 6 SMR 1 STRING 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11821425

Title: Molecular cloning and characterization of a novel UDP-GlcNAc:GalNAc-peptide beta1,3-N-acetylglucosaminyltransferase (beta 3Gn-T6), an enzyme synthesizing the core 3 structure of O-glycans.

PubMed ID: 11821425

DOI: 10.1074/jbc.m112457200

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: 7655172

Title: Synthesis of O-glycan core 3: characterization of UDP-GlcNAc: GalNAc-R beta 3-N-acetyl-glucosaminyltransferase activity from colonic mucosal tissues and lack of the activity in human cancer cell lines.

PubMed ID: 7655172

DOI: 10.1093/glycob/5.3.351

PubMed ID: 15755813

Title: Core 3 synthase is down-regulated in colon carcinoma and profoundly suppresses the metastatic potential of carcinoma cells.

PubMed ID: 15755813

DOI: 10.1073/pnas.0407983102

Sequence Information:

  • Length: 384
  • Mass: 42748
  • Checksum: F76C4577D3008429
  • Sequence:
    • MAFPCRRSLT AKTLACLLVG VSFLALQQWF LQAPRSPREE RSPQEETPEG PTDAPAADEP 
PSELVPGPPC VANASANATA DFEQLPARIQ DFLRYRHCRH FPLLWDAPAK CAGGRGVFLL 
LAVKSAPEHY ERRELIRRTW GQERSYGGRP VRRLFLLGTP GPEDEARAER LAELVALEAR 
EHGDVLQWAF ADTFLNLTLK HLHLLDWLAA RCPHARFLLS GDDDVFVHTA NVVRFLQAQP 
PGRHLFSGQL MEGSVPIRDS WSKYFVPPQL FPGSAYPVYC SGGGFLLSGP TARALRAAAR 
HTPLFPIDDA YMGMCLERAG LAPSGHEGIR PFGVQLPGAQ QSSFDPCMYR ELLLVHRFAP 
YEMLLMWKAL HSPALSCDRG HRVS