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25  structures 1315  species 1  interaction 8949  sequences 81  architectures

Family: UDPGT (PF00201)

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 / EGO
UDP-glucuronosyl and UDP-glucosyl transferase
PDB 1rrv EBI.jpg
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
SCOP 1rrv
SUPERFAMILY 1rrv

Uridine 5'-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT) is a 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]

Alternative names:

  • glucuronyltransferase
  • UDP-glucuronyl transferase
  • UDP-GT

Function[edit]

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 top 200 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,[3] 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.[4] 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[edit]

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.[5]

Genes[edit]

Human genes which encode UGT enzymes include:

References[edit]

  1. ^ 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. 
  2. ^ King C, Rios G, Green M, Tephly T (2000). "UDP-glucuronosyltransferases". Curr Drug Metab 1 (2): 143–161. doi:10.2174/1389200003339171. PMID 11465080. 
  3. ^ Court MH and 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. 
  4. ^ 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. 
  5. ^ 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. 

External links[edit]

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

UDP-glucoronosyl and UDP-glucosyl transferase Provide feedback

No Pfam abstract.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002213

UDP glycosyltransferases (UGT) are a superfamily of enzymes that catalyzes 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 catalyze 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.
  • 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 catalyzes 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 [PUBMED:] that catalyzes the transfer of glucose from UDP-glucose to a flavanol. This reaction is essential and one of the last steps in anthocyanin pigment biosynthesis.
  • Baculoviruses ecdysteroid UDP-glucosyltransferase (EC) [PUBMED:2505387] (egt). This enzyme catalyzes 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 inactivates macrolide anitibiotics via 2'-O-glycosylation using UDP-glucose.

These enzymes share a conserved domain of about 50 amino acid residues located in their C-terminal section.

Gene Ontology

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Domain organisation

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Alignments

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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
(14)
Full
(8949)
Representative proteomes NCBI
(9465)
Meta
(106)
RP15
(1059)
RP35
(2520)
RP55
(3921)
RP75
(4768)
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Format an alignment

  Seed
(14)
Full
(8949)
Representative proteomes NCBI
(9465)
Meta
(106)
RP15
(1059)
RP35
(2520)
RP55
(3921)
RP75
(4768)
Alignment:
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  Seed
(14)
Full
(8949)
Representative proteomes NCBI
(9465)
Meta
(106)
RP15
(1059)
RP35
(2520)
RP55
(3921)
RP75
(4768)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Family
Author: Finn RD
Number in seed: 14
Number in full: 8949
Average length of the domain: 279.00 aa
Average identity of full alignment: 18 %
Average coverage of the sequence by the domain: 62.32 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.5 19.5
Trusted cut-off 19.5 19.5
Noise cut-off 19.4 19.4
Model length: 500
Family (HMM) version: 13
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

UDPGT

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 25 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 seqence.

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