Details for: GAL3ST4

Gene ID: 79690

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: GAL3ST4

Ensembl ID: ENSG00000197093

Description: galactose-3-O-sulfotransferase 4

Cell Significance Landscape

Associated with

Significant Cells

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

  • myeloid leukocyte CL0000766
    CSI 6.01
    rCSI 5.54%
    PRS 99.53
  • monocyte CL0000576
    CSI 4.52
    rCSI 8.17%
    PRS 99.43
  • elicited macrophage CL0000861
    CSI 3.62
    rCSI 3.32%
    PRS 99.71
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 3.25
    rCSI 3.31%
    PRS 99.47
  • basal cell of epidermis CL0002187
    CSI 1.66
    rCSI 2.94%
    PRS 87.5
  • mesenchymal cell CL0008019
    CSI 1.35
    rCSI 3.43%
    PRS 98.8

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

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • 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 [GAL3ST4](/details-gene/79690) encodes Galactose-3-O-sulfotransferase 4, an enzyme located in the Golgi apparatus that catalyzes the transfer of sulfate to galactose residues. Its core molecular function involves the sulfation of O-linked glycans on glycoproteins and glycolipids ([GO:0050694](https://www.ebi.ac.uk/QuickGO/term/GO:0050694), [GO:0001733](https://www.ebi.ac.uk/QuickGO/term/GO:0001733)), a critical post-translational modification step in several biosynthetic pathways ([Link](https://doi.org/10.1074/jbc.m101558200)). **Overall**, expression data reveals its highest significance in cells of the myeloid lineage, including [myeloid leukocytes](/details-cell/CL0000766) and [monocytes](/details-cell/CL0000576), suggesting a specialized role in the function and regulation of the innate immune system. ## Cellular Roles and Expression Landscape The expression profile of [GAL3ST4](/details-gene/79690) is most pronounced within the hematopoietic system, particularly in the myeloid compartment. The gene shows the highest significance in [myeloid leukocytes](/details-cell/CL0000766) (CSI: 6.01), their precursor [monocytes](/details-cell/CL0000576) (CSI: 4.52), and differentiated [elicited macrophages](/details-cell/CL0000861) (CSI: 3.62). This strong and consistent association suggests that sulfation modifications catalyzed by [GAL3ST4](/details-gene/79690) are fundamentally important for the biological activities of these key innate immune cells, such as cell-cell recognition and signaling. Beyond the myeloid lineage, the gene also demonstrates notable significance in developing T-lymphocytes, specifically [double-positive, alpha-beta thymocytes](/details-cell/CL0000809) (CSI: 3.25). This points to a potential, though less dominant, role in the adaptive immune system, perhaps during T-cell maturation in the thymus. Additionally, its expression in non-hematopoietic cells such as [basal cells of the epidermis](/details-cell/CL0002187) and [mesenchymal cells](/details-cell/CL0008019) indicates that its function in modifying the glycan structures of proteins and lipids may also contribute to tissue maintenance and development. ## Pathways and Molecular Function [GAL3ST4](/details-gene/79690) is a sulfotransferase that utilizes 3'-phosphoadenosine 5'-phosphosulfate ([GO:0050656](https://www.ebi.ac.uk/QuickGO/term/GO:0050656)) as a sulfate donor to modify galactose residues on glycoconjugates. This enzymatic activity is central to the [glycoprotein biosynthetic process](/details-cell/GO:0009101), [glycolipid biosynthetic process](/details-cell/GO:0009247), and [proteoglycan biosynthetic process](/details-cell/GO:0030166). The resulting sulfated glycans are crucial components of the cell surface and extracellular matrix, mediating a wide range of biological interactions. The functional outcome of this activity is directly linked to [cell-cell signaling](/details-cell/GO:0007267), a process highly dependent on the precise structure of cell surface receptors and ligands. This is consistent with the gene's high significance in immune cells like [monocytes](/details-cell/CL0000576), which rely on specific surface molecule interactions for migration, activation, and pathogen recognition. The enzyme's primary localization to the [Golgi cisterna membrane](/details-cell/GO:0032580) is the expected subcellular site for these modifications. Furthermore, its identification in [extracellular exosomes](/details-cell/GO:0070062) suggests that molecules modified by [GAL3ST4](/details-gene/79690) may be secreted to participate in intercellular communication at a distance. ## Research Directions The specific expression pattern of [GAL3ST4](/details-gene/79690) in immune cells, coupled with its known biochemical function, suggests several avenues for future research. **Proposed Hypotheses:** 1. The sulfation of cell surface glycoproteins or glycolipids by [GAL3ST4](/details-gene/79690) in [monocytes](/details-cell/CL0000576) and [macrophages](/details-cell/CL0000861) creates specific binding sites for adhesion molecules (e.g., selectins) on endothelial cells, thereby acting as a critical regulator of leukocyte trafficking and extravasation during inflammation. 2. In [double-positive, alpha-beta thymocytes](/details-cell/CL0000809), [GAL3ST4](/details-gene/79690)-mediated glycosylation of the T-cell receptor (TCR) or associated co-receptors fine-tunes the sensitivity of the TCR to self-peptide-MHC complexes, thus influencing the threshold for positive and negative selection and shaping the mature T-cell repertoire. **Suggested Experimental Approach:** To test the first hypothesis regarding monocyte adhesion, one could employ a CRISPR-Cas9-based knockout of [GAL3ST4](/details-gene/79690) in a human monocytic cell line (e.g., THP-1). The adhesion capacity of these knockout cells versus wild-type controls could be directly compared using an in vitro flow chamber assay with a monolayer of activated endothelial cells (HUVECs). A reduction in adhesion in the knockout cells would support the hypothesis. Subsequent glycoproteomic analysis of the cell surface of both cell types would help identify the specific molecular substrates of [GAL3ST4](/details-gene/79690) responsible for the adhesion phenotype. **Therapeutic Potential:** As an intracellular enzyme located in the Golgi, [GAL3ST4](/details-gene/79690) is not a direct target for antibody-based therapies. However, its role as a key modifier of cell surface molecules essential for immune cell function makes it a potential target for small molecule inhibitors. If its activity is proven to be a rate-limiting step in the recruitment of inflammatory [monocytes](/details-cell/CL0000576) in chronic inflammatory or autoimmune diseases, **inhibition** of its sulfotransferase activity could serve as a novel anti-inflammatory strategy to selectively block pathological immune cell infiltration.

Genular Protein ID: 4170270376

Symbol: G3ST4_HUMAN

Name: Galactose-3-O-sulfotransferase 4

UniProtKB Accession Codes:

Q96RP7 A4D2A8 B4DWL8 D6W5U5 Q8N3P7 Q8WZ17 Q96E33 Q9HA78

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 11 Ensembl 2 ExpressionAtlas 1 GO 14 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 NIAGADS 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 2 RNAct 1 RefSeq 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 11333265

Title: Molecular cloning and characterization of a novel human galactose 3-O-sulfotransferase that transfers sulfate to Galbeta1->3GalNAc residue in O-glycans.

PubMed ID: 11333265

DOI: 10.1074/jbc.m101558200

PubMed ID: 15498874

Title: Large-scale cDNA transfection screening for genes related to cancer development and progression.

PubMed ID: 15498874

DOI: 10.1073/pnas.0404089101

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

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

Sequence Information:

  • Length: 486
  • Mass: 54166
  • Checksum: 2D731D16B191CC3C
  • Sequence:
    • MGPLSPARTL RLWGPRSLGV ALGVFMTIGF ALQLLGGPFQ RRLPGLQLRQ PSAPSLRPAL 
PSCPPRQRLV FLKTHKSGSS SVLSLLHRYG DQHGLRFALP ARYQFGYPKL FQASRVKGYR 
PQGGGTQLPF HILCHHMRFN LKEVLQVMPS DSFFFSIVRD PAALARSAFS YYKSTSSAFR 
KSPSLAAFLA NPRGFYRPGA RGDHYARNLL WFDFGLPFPP EKRAKRGNIH PPRDPNPPQL 
QVLPSGAGPR AQTLNPNALI HPVSTVTDHR SQISSPASFD LGSSSFIQWG LAWLDSVFDL 
VMVAEYFDES LVLLADALCW GLDDVVGFMH NAQAGHKQGL STVSNSGLTA EDRQLTARAR 
AWNNLDWALY VHFNRSLWAR IEKYGQGRLQ TAVAELRARR EALAKHCLVG GEASDPKYIT 
DRRFRPFQFG SAKVLGYILR SGLSPQDQEE CERLATPELQ YKDKLDAKQF PPTVSLPLKT 
SRPLSP