Summary: UDP-glucoronosyl and UDP-glucosyl transferase
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This is the Wikipedia entry entitled "Glucuronosyltransferase". More...
Glucuronosyltransferase Edit Wikipedia article
| Glucuronosyltransferase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 2.4.1.17 | ||||||||
| CAS number | 9030-08-4 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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| UDP-glucuronosyl and UDP-glucosyl transferase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Structure of TDP-vancosaminyltransferase GtfD as a complex with TDP and the natural substrate, desvancosaminyl vancomycin.[1] | |||||||||
| Identifiers | |||||||||
| Symbol | UDPGT | ||||||||
| Pfam | PF00201 | ||||||||
| InterPro | IPR002213 | ||||||||
| PROSITE | PDOC00359 | ||||||||
| SCOPe | 1rrv / SUPFAM | ||||||||
| Membranome | 476 | ||||||||
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Uridine 5'-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT) is a microsomal glycosyltransferase (EC 2.4.1.17) that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is a glucuronidation reaction.[2][3]
Alternative names:
- glucuronyltransferase
- UDP-glucuronyl transferase
- UDP-GT
Function
Glucuronosyltransferases are responsible for the process of glucuronidation, a major part of phase II metabolism. Arguably the most important of the Phase II (conjugative) enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s.
The reaction catalyzed by the UGT enzyme involves the addition of a glucuronic acid moiety to xenobiotics and is the most important pathway for the human body's elimination of the most frequently prescribed drugs. It is also the major pathway for foreign chemical (dietary, environmental, pharmaceutical) removal for most drugs, dietary substances, toxins and endogenous substances. UGT is present in humans, other animals, plants, and bacteria. Famously, UGT enzymes are not present in the genus Felis,[4] and this accounts for a number of unusual toxicities in the cat family.
The glucuronidation reaction consists of the transfer of the glucuronosyl group from uridine 5'-diphospho-glucuronic acid (UDPGA) to substrate molecules that contain oxygen, nitrogen, sulfur or carboxyl functional groups.[5] The resulting glucuronide is more polar (e.g. hydrophilic) and more easily excreted than the substrate molecule. The product solubility in blood is increased allowing it to be eliminated from the body by the kidneys.
Diseases
A deficiency in the bilirubin specific form of glucuronosyltransferase is thought to be the cause of Gilbert's syndrome, which is characterized by unconjugated hyperbilirubinemia.
It is also associated with Crigler–Najjar syndrome, a more serious disorder where the enzyme's activity is either completely absent (Crigler–Najjar syndrome type I) or less than 10% of normal (type II).
Infants may have a developmental deficiency in UDP-glucuronyl transferase, and are unable to hepatically metabolize the antibiotic drug chloramphenicol which requires glucuronidation. This leads to a condition known as gray baby syndrome.[6]
Causes
Causes of unconjugated hyperbilirubinemia are divided into three main categories, namely, excessive bilirubin synthesis, liver bilirubin uptake malfunction, and bilirubin conjugation compromise.[7]
As to excessive bilirubin synthesis, both intravascular hemolysis and extravascular hemolysis can involve in the pathophysiology.[7] Additionally, dyserythropoiesis and extravasation of blood into tissues such as angioedema and edema can also lead to indirect hyperbilirubinemia, along with heart failure, medication-induced, ethinyl estradiol, chronic hepatitis, and cirrhosis that are, otherwise, attributed to hepatic bilirubin mal-uptake and bilirubin conjugation compromise, respectively.[7]
Genes
Human genes which encode UGT enzymes include:
- B3GAT1, B3GAT2, B3GAT3
- UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10
- UGT2A1, UGT2A2, UGT2A3, UGT2B4, UGT2B7, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28
References
- ^ Mulichak AM, Lu W, Losey HC, Walsh CT, Garavito RM (May 2004). "Crystal structure of vancosaminyltransferase GtfD from the vancomycin biosynthetic pathway: interactions with acceptor and nucleotide ligands". Biochemistry. 43 (18): 5170–5180. doi:10.1021/bi036130c. PMID 15122882.
- ^ King C, Rios G, Green M, Tephly T (2000). "UDP-glucuronosyltransferases". Curr Drug Metab. 1 (2): 143–161. doi:10.2174/1389200003339171. PMID 11465080.
- ^ "UDP-glucuronosyltransferase 1-1". Drugbank. Retrieved 21 November 2019.
- ^ Court MH; Greenblatt DJ (2000). "Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms". Pharmacogenetics. 10 (4): 355–69. doi:10.1097/00008571-200006000-00009. PMID 10862526.
- ^ Bock K, Köhle C (2005). "UDP-glucuronosyltransferase 1A6: structural, functional, and regulatory aspects". Methods Enzymol. 400: 57–75. doi:10.1016/S0076-6879(05)00004-2. PMID 16399343.
- ^ MacDougall, C; Chambers, HF (2011). "55". Protein Synthesis Inhibitors and Miscellaneous Antibacterial Agents. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics (12 ed.). New York: McGraw-Hill. Retrieved October 19, 2011.
- ^ a b c Namita Roy-Chowdhury, PhD, FAASLDJayanta Roy-Chowdhury, MD, MRCP, AGAF, FAASLD. "Diagnostic approach to the adult with jaundice or asymptomatic hyperbilirubinemia". UpToDate. Section Editor:Sanjiv Chopra, MD, MACPDeputy Editor:Shilpa Grover, MD, MPH, AGAF. Retrieved 2019-07-17.CS1 maint: uses authors parameter (link) CS1 maint: others (link)
External links
- Glucuronosyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
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Internal database links
| SCOOP: | DUF1205 Glyco_tran_28_C Glyco_trans_1_3 Glyco_trans_1_4 Glyco_trans_4_4 Glyco_transf_28 Glyco_transf_4 Glycos_transf_1 |
| Similarity to PfamA using HHSearch: | Glyco_tran_28_C |
External database links
| CAZY: | GT1 |
| PROSITE: | PDOC00359 |
This tab holds annotation information from the InterPro database.
InterPro entry IPR002213
UDP glycosyltransferases (UGT) are a superfamily of enzymes that catalyses the addition of the glycosyl group from a UTP-sugar to a small hydrophobic molecule. This family currently consist of:
- Mammalian UDP-glucuronosyl transferases ( EC ) (UDPGT) [ PUBMED:1909870 ]. A large family of membrane-bound microsomal enzymes which catalyse the transfer of glucuronic acid to a wide variety of exogenous and endogenous lipophilic substrates. These enzymes are of major importance in the detoxification and subsequent elimination of xenobiotics such as drugs and carcinogens. These enzymes are also involved in cancer progression and drug resistance [ PUBMED:32047295 ].
- A large number of putative UDPGT from Caenorhabditis elegans.
- Mammalian 2-hydroxyacylsphingosine 1-beta-galactosyltransferase [ PUBMED:7694285 ] ( EC ) (also known as UDP-galactose-ceramide galactosyltransferase). This enzyme catalyses the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central nervous system and peripheral nervous system.
- Plants flavonol O(3)-glucosyltransferase ( EC ). An enzyme that catalyses the transfer of glucose from UDP-glucose to a flavanol. This reaction is essential and one of the last steps in anthocyanin pigment biosynthesis.
- (R)-mandelonitrile beta-glucosyltransferase from almond, which is involved in the biosynthesis of the cyanogenic glycoside (R)-prunasin (stereo-selective), a precursor of (R)-amygdalin which at high concentrations is associated with bitterness in kernels of almond [ PUBMED:32688778 ].
- Baculoviruses ecdysteroid UDP-glucosyltransferase ( EC ) [ PUBMED:2505387 ] (egt). This enzyme catalyses the transfer of glucose from UDP-glucose to ectysteroids which are insect molting hormones. The expression of egt in the insect host interferes with the normal insect development by blocking the molting process.
- Prokaryotic zeaxanthin glucosyltransferase ( EC ) (gene crtX), an enzyme involved in carotenoid biosynthesis and that catalyses the glycosylation reaction which converts zeaxanthin to zeaxanthin-beta-diglucoside.
- Streptomyces macrolide glycosyltransferases ( EC ) [ PUBMED:8244027 ]. These enzymes specifically inactivate macrolide antibiotics via 2'-O-glycosylation using UDP-glucose.
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
| Molecular function | UDP-glycosyltransferase activity (GO:0008194) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan GT-B (CL0113), which has the following description:
This is the GT-B clan that contains diverse glycosyltransferases that possess a Rossmann like fold [1].
The clan contains the following 48 members:
A-2_8-polyST AGT ALG11_N Alg14 Asp1 Capsule_synth DUF1205 DUF1972 DUF3492 DUF354 Epimerase_2 FucT_N FUT8_N_cat Glyco_tran_28_C Glyco_trans_1_2 Glyco_trans_1_3 Glyco_trans_1_4 Glyco_trans_4_2 Glyco_trans_4_3 Glyco_trans_4_4 Glyco_trans_4_5 Glyco_transf_10 Glyco_transf_20 Glyco_transf_28 Glyco_transf_4 Glyco_transf_41 Glyco_transf_5 Glyco_transf_52 Glyco_transf_56 Glyco_transf_9 Glyco_transf_90 Glycogen_syn Glycos_transf_1 Glycos_transf_N Glyphos_transf LpxB MGDG_synth Mito_fiss_Elm1 NodZ O-FucT Phosphorylase PIGA PM0188 PS_pyruv_trans SUA5 Sucrose_synth T4-Gluco-transf UDPGTAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
| Seed (13) |
Full (42599) |
Representative proteomes | UniProt (79758) |
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| RP15 (6285) |
RP35 (22384) |
RP55 (37056) |
RP75 (49926) |
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| Jalview | |||||||
| HTML | |||||||
| PP/heatmap | 1 | ||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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| Seed (13) |
Full (42599) |
Representative proteomes | UniProt (79758) |
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|---|---|---|---|---|---|---|---|
| RP15 (6285) |
RP35 (22384) |
RP55 (37056) |
RP75 (49926) |
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| Raw Stockholm | |||||||
| Gzipped | |||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Prosite |
| Previous IDs: | none |
| Type: | Family |
| Sequence Ontology: | SO:0100021 |
| Author: |
Finn RD 
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| Number in seed: | 13 |
| Number in full: | 42599 |
| Average length of the domain: | 242.00 aa |
| Average identity of full alignment: | 19 % |
| Average coverage of the sequence by the domain: | 52.22 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 499 | ||||||||||||
| Family (HMM) version: | 20 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the UDPGT domain has been found. There are 128 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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