Details for: UGT2B17

Gene ID: 7367

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: UGT2B17

Ensembl ID: ENSG00000197888

Description: UDP glucuronosyltransferase family 2 member B17

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • transit amplifying cell of colon CL0009011
    CSI 41.81
    rCSI 49.1%
    PRS 97.91
  • goblet cell CL0000160
    CSI 23.89
    rCSI 22.57%
    PRS 96.54
  • intestine goblet cell CL0019031
    CSI 21.53
    rCSI 19.11%
    PRS 96.58
  • colon epithelial cell CL0011108
    CSI 21.23
    rCSI 22.24%
    PRS 96.78
  • enterocyte of epithelium of large intestine CL0002071
    CSI 16.3
    rCSI 85.57%
    PRS 97.88
  • enterocyte CL0000584
    CSI 16.19
    rCSI 26.11%
    PRS 95.63
  • BEST4+ enteroycte CL4030026
    CSI 15.79
    rCSI 19.65%
    PRS 96.98
  • type L enteroendocrine cell CL0002279
    CSI 14.84
    rCSI 27.85%
    PRS 97.23
  • brush cell CL0002204
    CSI 14.28
    rCSI 28.27%
    PRS 97.43
  • colonocyte CL1000347
    CSI 13.49
    rCSI 19.34%
    PRS 96.69
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 13.29
    rCSI 35.83%
    PRS 98.09
  • transit amplifying cell CL0009010
    CSI 12.47
    rCSI 19.07%
    PRS 98.34
  • enteroendocrine cell CL0000164
    CSI 11.49
    rCSI 15.7%
    PRS 96.22
  • basal cell of epidermis CL0002187
    CSI 11.47
    rCSI 20.33%
    PRS 78.83
  • intestinal crypt stem cell of colon CL0009043
    CSI 11.47
    rCSI 86.11%
    PRS 98.8
  • paneth cell CL0000510
    CSI 10.02
    rCSI 14.79%
    PRS 98.68
  • paneth cell of epithelium of small intestine CL1000343
    CSI 8.76
    rCSI 24.56%
    PRS 98.24
  • enteroendocrine cell of small intestine CL0009006
    CSI 7.39
    rCSI 16.27%
    PRS 97.61
  • type EC enteroendocrine cell CL0000577
    CSI 4.57
    rCSI 16.23%
    PRS 97.25
  • tuft cell of colon CL0009041
    CSI 4.29
    rCSI 9.99%
    PRS 97.3
  • small intestine goblet cell CL1000495
    CSI 3.66
    rCSI 8.01%
    PRS 97.91
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 3.42
    rCSI 4.14%
    PRS 84.46
  • intestinal epithelial cell CL0002563
    CSI 2.33
    rCSI 2.43%
    PRS 96.45
  • transit amplifying cell of small intestine CL0009012
    CSI 1.93
    rCSI 8.47%
    PRS 98.29

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 [UGT2B17](/details-gene/7367) encodes UDP Glucuronosyltransferase Family 2 Member B17, an enzyme localized to the endoplasmic reticulum membrane that plays a critical role in the metabolism of endogenous and exogenous compounds. It is a key enzyme in Phase II biotransformation, specifically catalyzing the glucuronidation of C19 steroids, such as testosterone and dihydrotestosterone, as well as various xenobiotics ([Link](https://doi.org/10.1074/jbc.271.37.22855)). Expression data highlights its profound significance in the gastrointestinal tract, with particularly high expression in the epithelial cells of the colon, including [transit amplifying cell of colon](/details-cell/CL0009011), [goblet cell](/details-cell/CL0000160), and [enterocyte of epithelium of large intestine](/details-cell/CL0002071). This expression pattern suggests a primary function in detoxifying compounds and regulating the local steroid hormone environment at a major biological barrier. Common genetic deletions of [UGT2B17](/details-gene/7367) have been associated with conditions like osteoporosis ([Link](https://doi.org/10.1016/j.ajhg.2008.10.006)), underscoring its importance in systemic steroid homeostasis. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [UGT2B17](/details-gene/7367) establishes it as a specialized metabolic enzyme predominantly active in the intestinal epithelium. The gene shows its highest significance in the [transit amplifying cell of colon](/details-cell/CL0009011) (CSI: 41.81), a highly proliferative cell type responsible for renewing the colon lining. This is complemented by high significance in mature and specialized epithelial cell types, including secretory [goblet cell](/details-cell/CL0000160) (CSI: 23.89), absorptive [enterocyte](/details-cell/CL0000584) (CSI: 16.19), and hormone-producing [enteroendocrine cell](/details-cell/CL0000164) (CSI: 11.49). The gene's prominence extends to the progenitor compartment, with significant expression in both [intestinal crypt stem cell of small intestine](/details-cell/CL0009017) (CSI: 13.29) and [intestinal crypt stem cell of colon](/details-cell/CL0009043) (CSI: 11.47). This indicates that the metabolic machinery for steroid and xenobiotic glucuronidation is established early in the epithelial lineage and maintained throughout differentiation. A notable, albeit lower, significance in [basal cell of epidermis](/details-cell/CL0002187) (CSI: 11.47) suggests a broader role in other barrier tissues, though its primary functional arena appears to be the gut. ## Pathways and Molecular Function The molecular function of [UGT2B17](/details-gene/7367) is centered on its [Glucuronosyltransferase activity (GO:0015020)](https://www.ebi.ac.uk/QuickGO/term/GO:0015020), which is a cornerstone of several major metabolic pathways. It is an integral component of the [Glucuronidation (R-HSA-156588)](https://reactome.org/content/detail/R-HSA-156588) pathway, a key process in [Phase ii - conjugation of compounds (R-HSA-156580)](https://reactome.org/content/detail/R-HSA-156580). This process involves attaching glucuronic acid to substrates, increasing their water solubility and facilitating their excretion. Consistent with its known substrates, the gene is heavily involved in the [Steroid metabolic process (GO:0008202)](https://www.ebi.ac.uk/QuickGO/term/GO:0008202) and [Estrogen metabolic process (GO:0008210)](https://www.ebi.ac.uk/QuickGO/term/GO:0008210). It demonstrates specificity for various androgens and estrogens, influencing their bioavailability and activity ([Link](https://doi.org/10.1124/dmd.108.024844), [Link](https://doi.org/10.1124/dmd.112.049072)). Furthermore, its role in the [Xenobiotic metabolic process (GO:0006805)](https://www.ebi.ac.uk/QuickGO/term/GO:0006805) is highlighted by its participation in pathways for drug absorption, distribution, metabolism, and excretion (ADME), such as [Aspirin adme (R-HSA-9749641)](https://reactome.org/content/detail/R-HSA-9749641) and [Prednisone adme (R-HSA-9757110)](https://reactome.org/content/detail/R-HSA-9757110). These functions are carried out within the [Endoplasmic reticulum membrane (GO:0005789)](https://www.ebi.ac.uk/QuickGO/term/GO:0005789), where the enzyme is located. ## Research Directions The high expression of [UGT2B17](/details-gene/7367) in the colonic epithelium, a tissue where steroid hormones can influence cell proliferation and inflammation, opens several avenues for investigation. The gene's role at the interface of host metabolism, gut microbiome activity, and dietary exposures is of particular interest. ### Proposed Hypotheses: 1. **[UGT2B17](/details-gene/7367) activity in colonic crypt and transit-amplifying cells modulates the local androgen microenvironment, thereby regulating epithelial proliferation and potentially influencing the development or progression of hormone-sensitive colorectal cancers.** Its presence in these proliferative compartments suggests it may control the levels of steroids that act as growth factors. 2. **Inter-individual variation in [UGT2B17](/details-gene/7367) expression or function in enterocytes is a key determinant of the efficacy and toxicity of orally administered drugs that are substrates for glucuronidation.** This could explain why different individuals respond differently to the same dose of certain medications metabolized in the gut. ### Experimental Approach: To test the first hypothesis regarding its role in regulating proliferation, a robust experimental model would involve human colon organoids. Organoids could be generated from individuals with the functional [UGT2B17](/details-gene/7367) gene and from those with the common homozygous deletion. These two groups of organoids would be cultured with and without physiological levels of C19 steroids (e.g., testosterone). The impact on proliferation could be directly measured by EdU incorporation assays and immunohistochemistry for Ki67. Concurrently, liquid chromatography-mass spectrometry (LC-MS) analysis of the culture supernatant would quantify the conversion of testosterone to its glucuronidated metabolite, directly linking enzymatic activity to the observed cellular phenotype. ### Therapeutic Potential: As a metabolic enzyme, [UGT2B17](/details-gene/7367) presents a complex therapeutic profile. Widespread inhibition would likely be detrimental, as it would impair detoxification of numerous endogenous and exogenous compounds. However, in specific pathological contexts, such as hormone-driven colorectal cancer, targeted inhibition could be a viable strategy. If [UGT2B17](/details-gene/7367) is found to inactivate anti-proliferative steroids or, conversely, activate pro-proliferative precursors within the tumor microenvironment, a highly specific inhibitor could sensitize tumors to other therapies or slow their growth. Therefore, its therapeutic potential is likely context-dependent and would likely involve **inhibition** rather than activation, requiring careful consideration of on-target and off-target effects on drug and steroid metabolism.

Genular Protein ID: 284718848

Symbol: UDB17_HUMAN

Name: C19-steroid-specific UDP-glucuronosyltransferase

UniProtKB Accession Codes:

O75795

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CAZy 1 CCDS 1 CDD 1 CTD 1 ChEBI 30 ChEMBL 1 DNASU 1 DisGeNET 1 DrugBank 11 EC 1 EMBL 1 Ensembl 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 2 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 Rhea 12 SABIO-RK 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8798464

Title: Isolation and characterization of a novel cDNA encoding a human UDP-glucuronosyltransferase active on C19 steroids.

PubMed ID: 8798464

DOI: 10.1074/jbc.271.37.22855

PubMed ID: 9364925

Title: Chromosomal localization, structure, and regulation of the UGT2B17 gene, encoding a C19 steroid metabolizing enzyme.

PubMed ID: 9364925

DOI: 10.1089/dna.1997.16.1143

PubMed ID: 16595710

Title: Human UDP-glucuronosyltransferase, UGT1A8, glucuronidates dihydrotestosterone to a monoglucuronide and further to a structurally novel diglucuronide.

PubMed ID: 16595710

DOI: 10.1124/dmd.106.009621

PubMed ID: 18719240

Title: The configuration of the 17-hydroxy group variably influences the glucuronidation of beta-estradiol and epiestradiol by human UDP-glucuronosyltransferases.

PubMed ID: 18719240

DOI: 10.1124/dmd.108.022731

PubMed ID: 18992858

Title: Genome-wide copy-number-variation study identified a susceptibility gene, UGT2B17, for osteoporosis.

PubMed ID: 18992858

DOI: 10.1016/j.ajhg.2008.10.006

PubMed ID: 19022937

Title: UDP-glucuronosyltransferases (UGTs) 2B7 and UGT2B17 display converse specificity in testosterone and epitestosterone glucuronidation, whereas UGT2A1 conjugates both androgens similarly.

PubMed ID: 19022937

DOI: 10.1124/dmd.108.024844

PubMed ID: 23288867

Title: Regiospecificity and stereospecificity of human UDP-glucuronosyltransferases in the glucuronidation of estriol, 16-epiestriol, 17-epiestriol, and 13-epiestradiol.

PubMed ID: 23288867

DOI: 10.1124/dmd.112.049072

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 530
  • Mass: 61095
  • Checksum: 8E59EBC43CF43760
  • Sequence:
    • MSLKWMSVFL LMQLSCYFSS GSCGKVLVWP TEYSHWINMK TILEELVQRG HEVIVLTSSA 
SILVNASKSS AIKLEVYPTS LTKNDLEDFF MKMFDRWTYS ISKNTFWSYF SQLQELCWEY 
SDYNIKLCED AVLNKKLMRK LQESKFDVLL ADAVNPCGEL LAELLNIPFL YSLRFSVGYT 
VEKNGGGFLF PPSYVPVVMS ELSDQMIFME RIKNMIYMLY FDFWFQAYDL KKWDQFYSEV 
LGRPTTLFET MGKAEMWLIR TYWDFEFPRP FLPNVDFVGG LHCKPAKPLP KEMEEFVQSS 
GENGIVVFSL GSMISNMSEE SANMIASALA QIPQKVLWRF DGKKPNTLGS NTRLYKWLPQ 
NDLLGHPKTK AFITHGGTNG IYEAIYHGIP MVGIPLFADQ HDNIAHMKAK GAALSVDIRT 
MSSRDLLNAL KSVINDPIYK ENIMKLSRIH HDQPVKPLDR AVFWIEFVMR HKGAKHLRVA 
AHNLTWIQYH SLDVIAFLLA CVATMIFMIT KCCLFCFRKL AKTGKKKKRD