Details for: POGLUT1

Gene ID: 56983

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: POGLUT1

Ensembl ID: ENSG00000163389

Description: protein O-glucosyltransferase 1

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • hepatocyte CL0000182
    CSI 10.11
    rCSI 18.09%
    PRS 76.84
  • cardiac muscle cell CL0000746
    CSI 7.31
    rCSI 10.49%
    PRS 67.43
  • double negative thymocyte CL0002489
    CSI 4.65
    rCSI 3.24%
    PRS 88.64
  • central memory CD4-positive, alpha-beta T cell CL0000904
    CSI 4.16
    rCSI 2.46%
    PRS 92.41
  • Kupffer cell CL0000091
    CSI 3.42
    rCSI 7.82%
    PRS 78.54
  • melanocyte CL0000148
    CSI 3.38
    rCSI 2.5%
    PRS 70.96
  • early lymphoid progenitor CL0000936
    CSI 3.34
    rCSI 2.93%
    PRS 82.71
  • secretory cell CL0000151
    CSI 3.17
    rCSI 3.31%
    PRS 76.93
  • regular ventricular cardiac myocyte CL0002131
    CSI 3.11
    rCSI 19.44%
    PRS 69.32
  • neural crest cell CL0011012
    CSI 2.91
    rCSI 2.3%
    PRS 65.95
  • amacrine cell CL0000561
    CSI 2.85
    rCSI 8.27%
    PRS 66.99
  • dendritic cell, human CL0001056
    CSI 2.79
    rCSI 4.29%
    PRS 86.11
  • mesodermal cell CL0000222
    CSI 2.79
    rCSI 3.35%
    PRS 75.34
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.72
    rCSI 3.38%
    PRS 57.3
  • astrocyte of the cerebral cortex CL0002605
    CSI 2.64
    rCSI 5.92%
    PRS 60.18
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 2.62
    rCSI 1.76%
    PRS 90.02
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.59
    rCSI 4.14%
    PRS 81.34
  • hematopoietic stem cell CL0000037
    CSI 2.46
    rCSI 1.64%
    PRS 80.58
  • naive B cell CL0000788
    CSI 2.35
    rCSI 2.01%
    PRS 84.64
  • cerebral cortex endothelial cell CL1001602
    CSI 2.26
    rCSI 3.9%
    PRS 68.88
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 2.23
    rCSI 1.6%
    PRS 89.87
  • retinal bipolar neuron CL0000748
    CSI 2.17
    rCSI 4.06%
    PRS 65.76
  • hepatic stellate cell CL0000632
    CSI 2.07
    rCSI 7.74%
    PRS 69.94
  • hematopoietic precursor cell CL0008001
    CSI 2.05
    rCSI 2.11%
    PRS 89.55
  • chondrocyte CL0000138
    CSI 1.99
    rCSI 3.16%
    PRS 70.45
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 1.94
    rCSI 1.77%
    PRS 89.43
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.89
    rCSI 2.26%
    PRS 59.41
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.89
    rCSI 1.46%
    PRS 80.34
  • peripheral nervous system neuron CL2000032
    CSI 1.79
    rCSI 2.44%
    PRS 69.08
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.78
    rCSI 2.29%
    PRS 60.59
  • keratinocyte CL0000312
    CSI 1.75
    rCSI 1.47%
    PRS 80.63
  • Langerhans cell CL0000453
    CSI 1.73
    rCSI 2.64%
    PRS 88.79
  • type B pancreatic cell CL0000169
    CSI 1.66
    rCSI 3.67%
    PRS 76.98
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.42
    rCSI 2.51%
    PRS 58.64
  • myeloid dendritic cell CL0000782
    CSI 1.3
    rCSI 1.88%
    PRS 90.03
  • sncg GABAergic cortical interneuron CL4023015
    CSI 1.28
    rCSI 2.05%
    PRS 61.15
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.26
    rCSI 3.19%
    PRS 67.87
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.21
    rCSI 1.09%
    PRS 75.84
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.2
    rCSI 2.02%
    PRS 59.42
  • blood vessel smooth muscle cell CL0019018
    CSI 1.07
    rCSI 8.7%
    PRS 71.49
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.07
    rCSI 2.88%
    PRS 82.94
  • neural progenitor cell CL0011020
    CSI 0.95
    rCSI 4.19%
    PRS 66.21
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.79
    rCSI 1.92%
    PRS 57.45
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.79
    rCSI 2.83%
    PRS 57.38
  • podocyte CL0000653
    CSI 0.79
    rCSI 3.49%
    PRS 78.12
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 0.59
    rCSI 1.86%
    PRS 63.55
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.57
    rCSI 1.8%
    PRS 61.08
  • follicular dendritic cell CL0000442
    CSI 0.54
    rCSI 8.63%
    PRS 88.13
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.47
    rCSI 1.77%
    PRS 59.92
  • central nervous system neuron CL2000029
    CSI 0.3
    rCSI 2.22%
    PRS 64.77
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 0.29
    rCSI 1.74%
    PRS 60.25
  • direct pathway medium spiny neuron CL4023026
    CSI 0.27
    rCSI 6.43%
    PRS 57.85
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.21
    rCSI 5.02%
    PRS 58.4

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 [POGLUT1](/details-gene/56983) (Protein O-Glucosyltransferase 1) is a protein-coding gene located on chromosome 3q13.33. It encodes a crucial glycosyltransferase enzyme that resides in the endoplasmic reticulum. This enzyme is responsible for the O-linked glycosylation of serine residues within Epidermal Growth Factor (EGF)-like repeats, a key post-translational modification for proteins in the Notch signaling pathway. Its function is essential for proper protein folding and signaling activity, particularly during embryonic development. Expression data indicates that [POGLUT1](/details-gene/56983) is highly significant in diverse cell types, including [hepatocytes](/details-cell/CL0000182) and [cardiac muscle cells](/details-cell/CL0000746), suggesting broad roles in organ development and maintenance. Clinically, mutations in [POGLUT1](/details-gene/56983) are associated with autosomal-dominant Dowling-Degos disease, a skin pigmentation disorder, and a form of limb-girdle muscular dystrophy ([Link](https://doi.org/10.1016/j.ajhg.2013.12.003), [Link](https://doi.org/10.15252/emmm.201505815)). ## Cellular Roles and Expression Landscape The expression profile of [POGLUT1](/details-gene/56983) highlights its importance across multiple fundamental cell lineages. **Overall**, the gene shows the highest significance in [hepatocytes](/details-cell/CL0000182) (CSI: 10.11), suggesting a critical role in liver biology and metabolism. This is followed by strong significance in [cardiac muscle cells](/details-cell/CL0000746) (CSI: 7.31), which aligns with its known function in muscle development and the muscular dystrophy phenotype associated with its mutation ([Link](https://doi.org/10.15252/emmm.201505815)). A notable pattern of expression is also observed within the immune system, particularly during early lymphoid development. [POGLUT1](/details-gene/56983) is significant in [double negative thymocytes](/details-cell/CL0002489) (CSI: 4.65), [central memory CD4-positive, alpha-beta T cells](/details-cell/CL0000904) (CSI: 4.16), and [early lymphoid progenitors](/details-cell/CL0000936) (CSI: 3.34). This pattern is consistent with the well-established role of Notch signaling in regulating T-cell lineage commitment and differentiation within the thymus. Furthermore, its significance in developmental cell types such as [mesodermal cells](/details-cell/CL0000222) (CSI: 2.79) and [neural crest cells](/details-cell/CL0011012) (CSI: 2.91) underscores its foundational role in embryogenesis, which is strongly supported by its functional annotations related to gastrulation and somitogenesis. ## Pathways and Molecular Function The molecular function of [POGLUT1](/details-gene/56983) is centered on its enzymatic activity as a glycosyltransferase. It specifically catalyzes the transfer of glucose and xylose to serine residues on EGF-like domains, as detailed by its GO annotations for [Egf-domain serine glucosyltransferase activity](/details-go/GO:0140561) and [Egf-domain serine xylosyltransferase activity](/details-go/GO:0140562) ([Link](https://doi.org/10.1073/pnas.1109696108)). This activity occurs within the [endoplasmic reticulum lumen](/details-go/GO:0005788). The primary and most well-characterized substrate for [POGLUT1](/details-gene/56983) is the Notch receptor. Its involvement is critical for '[Pre-notch expression and processing](/details-reactome/R-HSA-1912422)' and the overarching '[Signaling by notch](/details-reactome/R-HSA-157118)' pathway. This post-translational modification is essential for the correct folding, trafficking, and ligand-binding affinity of Notch receptors, thereby positively regulating pathway activation ([Link](https://doi.org/10.1242/dev.060020)). This core molecular function explains the gene's implication in a wide array of biological processes. Its role in the [positive regulation of notch signaling pathway](/details-go/GO:0045747) is fundamental to developmental events such as [somitogenesis](/details-go/GO:0001756), [muscle tissue development](/details-go/GO:0060537), and [circulatory system development](/details-go/GO:0072359), which is consistent with its high expression in mesodermal and cardiac cell types. ## Research Directions The established role of [POGLUT1](/details-gene/56983) in Notch signaling, combined with its diverse expression profile, suggests several avenues for future investigation. **Proposed Hypotheses:** 1. Given the high significance of [POGLUT1](/details-gene/56983) in [hepatocytes](/details-cell/CL0000182) and the known role of Notch in liver zonation and regeneration, it is hypothesized that [POGLUT1](/details-gene/56983)-mediated glycosylation is a critical regulatory step in modulating Notch signaling during liver repair and homeostasis. Dysregulation of this process could contribute to liver pathologies. 2. The gene's significant expression in early T-cell developmental stages, such as [double negative thymocytes](/details-cell/CL0002489), suggests a hypothesis where [POGLUT1](/details-gene/56983) activity levels fine-tune Notch receptor sensitivity, thereby acting as a crucial checkpoint in controlling the fate decision between T-cell lineages (e.g., CD4 vs. CD8) in the thymus. **Experimental Approach:** To test the first hypothesis regarding its role in liver regeneration, a conditional knockout mouse model could be employed (e.g., using an Albumin-Cre driver to specifically delete [POGLUT1](/details-gene/56983) in hepatocytes). Following a controlled liver injury, such as partial hepatectomy, the regenerative capacity of knockout versus wild-type mice could be compared. Key assays would include histological analysis of liver architecture, quantification of hepatocyte proliferation (e.g., Ki-67 staining), and molecular assessment of Notch pathway activity (e.g., qPCR for target genes like *Hes1* and *Hey1*) in the regenerating liver tissue. **Therapeutic Potential:** Because known diseases associated with [POGLUT1](/details-gene/56983) are caused by loss-of-function mutations, therapeutic strategies would likely focus on restoring or augmenting its function rather than inhibition. As an intracellular enzyme located in the endoplasmic reticulum, it represents a challenging drug target for small molecules. Potential long-term strategies for associated muscular dystrophies or skin disorders could involve gene therapy to deliver a functional copy of the gene to affected tissues. Alternatively, small molecule chaperones or activators that enhance the function of partially active mutant proteins could be explored, though this would require detailed structural and functional studies of specific patient-derived mutations.

Genular Protein ID: 198966017

Symbol: PGLT1_HUMAN

Name: KTEL motif-containing protein 1

UniProtKB Accession Codes:

Q8NBL1 B2RD13 Q53GJ4 Q8N2T1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 2 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CAZy 1 CCDS 1 CPTAC 1 CTD 1 ChEBI 14 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 10 Ensembl 1 ExpressionAtlas 1 GO 18 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 6 PDBsum 6 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 6 SABIO-RK 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 UniPathway 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 16524674

Title: Cloning, expression and characterization of a novel human CAP10-like gene hCLP46 from CD34+ stem/progenitor cells.

PubMed ID: 16524674

DOI: 10.1016/j.gene.2005.08.027

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16303743

Title: Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries.

PubMed ID: 16303743

DOI: 10.1093/dnares/12.2.117

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

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: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 21490058

Title: Regulation of mammalian Notch signaling and embryonic development by the protein O-glucosyltransferase Rumi.

PubMed ID: 21490058

DOI: 10.1242/dev.060020

PubMed ID: 21081508

Title: Universal phosphatase-coupled glycosyltransferase assay.

PubMed ID: 21081508

DOI: 10.1093/glycob/cwq187

PubMed ID: 21949356

Title: Rumi functions as both a protein O-glucosyltransferase and a protein O-xylosyltransferase.

PubMed ID: 21949356

DOI: 10.1073/pnas.1109696108

PubMed ID: 24387993

Title: Mutations in POGLUT1, encoding protein O-glucosyltransferase 1, cause autosomal-dominant Dowling-Degos disease.

PubMed ID: 24387993

DOI: 10.1016/j.ajhg.2013.12.003

PubMed ID: 27807076

Title: A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss.

PubMed ID: 27807076

DOI: 10.15252/emmm.201505815

PubMed ID: 28775322

Title: Structural basis of Notch O-glucosylation and O-xylosylation by mammalian protein-O-glucosyltransferase 1 (POGLUT1).

PubMed ID: 28775322

DOI: 10.1038/s41467-017-00255-7

PubMed ID: 27479915

Title: Mutations in POGLUT1 in Galli-Galli/Dowling-Degos disease.

PubMed ID: 27479915

DOI: 10.1111/bjd.14914

Sequence Information:

  • Length: 392
  • Mass: 46189
  • Checksum: 25B0370757A6B224
  • Sequence:
    • MEWWASSPLR LWLLLFLLPS AQGRQKESGS KWKVFIDQIN RSLENYEPCS SQNCSCYHGV 
IEEDLTPFRG GISRKMMAEV VRRKLGTHYQ ITKNRLYREN DCMFPSRCSG VEHFILEVIG 
RLPDMEMVIN VRDYPQVPKW MEPAIPVFSF SKTSEYHDIM YPAWTFWEGG PAVWPIYPTG 
LGRWDLFRED LVRSAAQWPW KKKNSTAYFR GSRTSPERDP LILLSRKNPK LVDAEYTKNQ 
AWKSMKDTLG KPAAKDVHLV DHCKYKYLFN FRGVAASFRF KHLFLCGSLV FHVGDEWLEF 
FYPQLKPWVH YIPVKTDLSN VQELLQFVKA NDDVAQEIAE RGSQFIRNHL QMDDITCYWE 
NLLSEYSKFL SYNVTRRKGY DQIIPKMLKT EL

Genular Protein ID: 2284961114

Symbol: B4DJ97_HUMAN

Name: N/A

UniProtKB Accession Codes:

B4DJ97

Database IDs:

ARBA 4 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 5 InterPro 2 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 RefSeq 4 SMART 2 SMR 1 UniPathway 1

Sequence Information:

  • Length: 233
  • Mass: 27528
  • Checksum: 873C740A2148E621
  • Sequence:
    • MYPAWTFWEG GPAVWPIYPT GLGRWDLFRE DLVRSAAQWP WKKKNSTAYF RGSRTSPERD 
PLILLSRKNP KLVDAEYTKN QAWKSMKDTL GKPAAKDVHL VDHCKYKYLF NFRGVAASFR 
FKHLFLCGSL VFHVGDEWLE FFYPQLKPWV HYIPVKTDLS NVQELLQFVK ANDDVAQEIA 
ERGSQFIRNH LQMDDITCYW ENLLSEYSKF LSYNVTRRKG YDQIIPKMLK TEL