Details for: FUT4

Gene ID: 2526

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: FUT4

Ensembl ID: ENSG00000196371

Description: fucosyltransferase 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • goblet cell CL0000160
    CSI 6.85
    rCSI 6.47%
    PRS 95.04
  • pancreatic acinar cell CL0002064
    CSI 2.8
    rCSI 3.73%
    PRS 97.35
  • stem cell CL0000034
    CSI 2.77
    rCSI 2.68%
    PRS 94.94
  • promyelocyte CL0000836
    CSI 2.55
    rCSI 3.68%
    PRS 97.08
  • granulocyte monocyte progenitor cell CL0000557
    CSI 2.35
    rCSI 2.04%
    PRS 97.43
  • pancreatic ductal cell CL0002079
    CSI 1.66
    rCSI 3.23%
    PRS 96.62
  • promonocyte CL0000559
    CSI 1.56
    rCSI 2.67%
    PRS 97.24
  • colon goblet cell CL0009039
    CSI 1.49
    rCSI 3.55%
    PRS 96.68
  • basal cell of epidermis CL0002187
    CSI 1.43
    rCSI 2.54%
    PRS 75.26

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
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  • Node Size: Proportional to Target Cell CSI magnitude
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  • 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 [FUT4](/details-gene/2526) (Fucosyltransferase 4) is a protein-coding gene located on chromosome 11q21 that encodes an alpha-(1,3)-fucosyltransferase. This enzyme plays a crucial role in the final steps of glycosylation, specifically by catalyzing the addition of fucose to N-acetylglucosamine residues. This activity is essential for the synthesis of the Lewis x (CD15) antigen, a carbohydrate structure involved in cell-cell adhesion, immune cell trafficking, and differentiation. Expression data indicates that **`Overall`**, [FUT4](/details-gene/2526) is a highly significant gene in secretory epithelial cells, such as [goblet cells](/details-cell/CL0000160), and is also a key marker for myeloid lineage precursor cells, including [promyelocytes](/details-cell/CL0000836). Its function is clinically relevant and has been associated with OMIM entry [153245](https://omim.org/entry/104230). ## Cellular Roles and Expression Landscape The expression profile of [FUT4](/details-gene/2526) highlights its specialized role in glycosylation within specific cellular contexts. **`Overall`**, the gene shows the highest significance in professional secretory cells, with a particularly high Cell Significance Index (CSI) in [goblet cells](/details-cell/CL0000160) (CSI: 6.85) and [pancreatic acinar cells](/details-cell/CL0002064) (CSI: 2.80). This suggests a primary function in modifying secreted glycoproteins or glycolipids, such as mucins, which form protective barriers. Concurrently, [FUT4](/details-gene/2526) is a defining marker for early-stage myeloid development. It is highly significant in [promyelocytes](/details-cell/CL0000836) (CSI: 2.55), [granulocyte monocyte progenitor cells](/details-cell/CL0000557) (CSI: 2.35), and [promonocytes](/details-cell/CL0000559) (CSI: 1.56). This expression pattern is directly linked to its role in synthesizing the CD15 antigen (Lewis x), a critical surface marker used to identify and sort these cell populations. Research has shown that while other fucosyltransferases are active in mature granulocytes, [FUT4](/details-gene/2526) is specifically responsible for CD15 expression in [promyelocytes](/details-cell/CL0000836) and monocytes ([Link](https://doi.org/10.1074/jbc.m007272200)). This underscores its importance in myeloid differentiation and the acquisition of adhesion properties necessary for immune function. The gene's significance in [stem cells](/details-cell/CL0000034) (CSI: 2.77) further suggests a role in hematopoietic lineage commitment. ## Pathways and Molecular Function Functionally, [FUT4](/details-gene/2526) is an enzyme with '[alpha-(1->3)-fucosyltransferase activity](/details-cell/GO:0046920)' located primarily in the '[Golgi apparatus](/details-cell/GO:0005794)' and the '[cell surface](/details-cell/GO:0009986)'. Its main biological process is '[Fucosylation](/details-cell/GO:0036065)', the covalent attachment of fucose to other molecules. This enzymatic activity is central to the '[Lewis x epitope biosynthetic process](/details-cell/GO:0106402)', a pathway critical for cell recognition and adhesion. The Lewis x structure synthesized by [FUT4](/details-gene/2526) acts as a ligand for selectin proteins, which mediate the initial steps of leukocyte trafficking during inflammation. This is reflected in its annotation to processes such as '[Positive regulation of leukocyte tethering or rolling](/details-cell/GO:1903238)' and '[Regulation of leukocyte cell-cell adhesion](/details-cell/GO:1903037)'. The involvement in the '[Inflammatory response](/details-cell/GO:0006954)' is therefore a direct consequence of its role in enabling immune cell migration. Furthermore, its involvement in Reactome pathways like '[Lewis blood group biosynthesis](/details-cell/R-HSA-9037629)' highlights its broader role in determining cell surface carbohydrate landscapes. While some studies initially linked it to the E-selectin ligand ELAM-1 ([Link](https://doi.org/10.1016/0092-8674(90)90430-m)), later work clarified that it synthesizes Lewis x but may not be sufficient for conferring E-selectin dependent adhesion on its own ([Link](https://doi.org/10.1016/s0021-9258(19)47396-1), [Link](https://doi.org/10.1016/s0021-9258(18)54704-9)). ## Research Directions The specific expression pattern and enzymatic function of [FUT4](/details-gene/2526) suggest it plays a critical, context-dependent role in both mucosal homeostasis and immune cell biology. Its involvement in synthesizing adhesion molecules that mediate inflammation presents intriguing avenues for further research and therapeutic development. **Proposed Hypotheses:** 1. Given its high significance in [goblet cells](/details-cell/CL0000160) and its role in glycosylation, dysregulation of [FUT4](/details-gene/2526) in the intestinal epithelium may alter the glycosylation patterns of mucins, thereby compromising the mucosal barrier, modifying microbiota composition, and contributing to the pathogenesis of inflammatory bowel disease (IBD). 2. Based on its specific role in generating the CD15 epitope on myeloid precursors ([Link](https://doi.org/10.1074/jbc.m007272200)), aberrant [FUT4](/details-gene/2526) expression in hematopoietic malignancies, such as acute myeloid leukemia (AML), could serve as a biomarker for specific AML subtypes or contribute to leukemic cell adhesion and tissue infiltration. **Experimental Approach:** To test the first hypothesis regarding [FUT4](/details-gene/2526)'s role in IBD, an intestinal-specific conditional knockout mouse model could be generated (e.g., *Fut4flox/flox;Villin-Cre+*). These mice and littermate controls would be subjected to a chemically-induced colitis model, such as dextran sulfate sodium (DSS) administration. The severity of colitis would be assessed by monitoring weight loss, stool consistency, and histological scoring of colon tissue. Mucin glycosylation would be profiled using lectin staining and mass spectrometry to confirm altered fucosylation. Furthermore, 16S rRNA gene sequencing of fecal samples would be performed to determine if loss of [FUT4](/details-gene/2526)-mediated fucosylation leads to a dysbiotic gut microbiome that exacerbates inflammation. **Therapeutic Potential:** [FUT4](/details-gene/2526) represents a potential therapeutic target for **inhibition**. The carbohydrate structures it synthesizes are implicated in pathological processes, including tumor cell metastasis and excessive leukocyte recruitment in chronic inflammatory diseases. A small-molecule inhibitor targeting the enzymatic activity of [FUT4](/details-gene/2526) could serve as a novel anti-inflammatory agent by preventing the formation of selectin ligands on leukocytes, thereby blocking their extravasation into tissue. In oncology, such an inhibitor could potentially reduce the metastatic potential of cancers that rely on Lewis antigen-mediated adhesion for dissemination. As an intracellular Golgi-resident enzyme, targeting it presents challenges, but its specific role in key pathological pathways makes it an attractive candidate for drug development.

Genular Protein ID: 218749432

Symbol: FUT4_HUMAN

Name: Alpha-(1,3)-fucosyltransferase 4

UniProtKB Accession Codes:

P22083 B2RMS0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CAZy 1 CCDS 1 CTD 1 ChEBI 20 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 EC 1 EMBL 8 Ensembl 1 GO 25 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 8 SMR 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: 1702034

Title: ELFT: a gene that directs the expression of an ELAM-1 ligand.

PubMed ID: 1702034

DOI: 10.1016/0092-8674(90)90430-m

PubMed ID: 1716630

Title: Molecular cloning of a human fucosyltransferase gene that determines expression of the Lewis x and VIM-2 epitopes but not ELAM-1-dependent cell adhesion.

PubMed ID: 1716630

DOI: 10.1016/s0021-9258(19)47396-1

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: 1718983

Title: Cloning of a human alpha(1,3)-fucosyltransferase gene that encodes ELFT but does not confer ELAM-1 recognition on Chinese hamster ovary cell transfectants.

PubMed ID: 1718983

DOI: 10.1016/s0021-9258(18)54704-9

PubMed ID: 11278338

Title: CD15 expression in mature granulocytes is determined by alpha 1,3-fucosyltransferase IX, but in promyelocytes and monocytes by alpha 1,3-fucosyltransferase IV.

PubMed ID: 11278338

DOI: 10.1074/jbc.m007272200

PubMed ID: 29593094

Title: Distinct human alpha(1,3)-fucosyltransferases drive Lewis-X/sialyl Lewis-X assembly in human cells.

PubMed ID: 29593094

DOI: 10.1074/jbc.ra117.000775

Sequence Information:

  • Length: 530
  • Mass: 59084
  • Checksum: B10C1C3C67BE1562
  • Sequence:
    • MRRLWGAARK PSGAGWEKEW AEAPQEAPGA WSGRLGPGRS GRKGRAVPGW ASWPAHLALA 
ARPARHLGGA GQGPRPLHSG TAPFHSRASG ERQRRLEPQL QHESRCRSST PADAWRAEAA 
LPVRAMGAPW GSPTAAAGGR RGWRRGRGLP WTVCVLAAAG LTCTALITYA CWGQLPPLPW 
ASPTPSRPVG VLLWWEPFGG RDSAPRPPPD CRLRFNISGC RLLTDRASYG EAQAVLFHHR 
DLVKGPPDWP PPWGIQAHTA EEVDLRVLDY EEAAAAAEAL ATSSPRPPGQ RWVWMNFESP 
SHSPGLRSLA SNLFNWTLSY RADSDVFVPY GYLYPRSHPG DPPSGLAPPL SRKQGLVAWV 
VSHWDERQAR VRYYHQLSQH VTVDVFGRGG PGQPVPEIGL LHTVARYKFY LAFENSQHLD 
YITEKLWRNA LLAGAVPVVL GPDRANYERF VPRGAFIHVD DFPSASSLAS YLLFLDRNPA 
VYRRYFHWRR SYAVHITSFW DEPWCRVCQA VQRAGDRPKS IRNLASWFER