UGT1A9

Last updated

UGT1A9
Identifiers
Aliases UGT1A9 , HLUGP4, LUGP4, UDPGT, UDPGT 1-9, UGT-1I, UGT1-09, UGT1-9, UGT1.9, UGT1AI, UGT1I, UGT1A9S, UDP glucuronosyltransferase family 1 member A9
External IDs OMIM: 606434; MGI: 3580642; HomoloGene: 133281; GeneCards: UGT1A9; OMA:UGT1A9 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_021027

NM_201641

RefSeq (protein)

NP_066307

n/a

Location (UCSC) Chr 2: 233.67 – 233.77 Mb Chr 1: 87.98 – 88.15 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

UDP-glucuronosyltransferase 1-9 is an enzyme that in humans is encoded by the UGT1A9 gene. [5] [6] [7] [8]

Contents

Function

This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5′ exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene is active on phenols. [8]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [§ 1]

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IrinotecanPathway WP229.png go to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to article
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Irinotecan Pathway edit
  1. The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP229".

Medicinal Chemistry Case Studies

During hit optimization of HSD17B13 inhibitors significant glucuronidation of the phenol moiety was observed in vitro and in vivo. [9] UGT phenotyping revealed UGT1A9 as main contributor for glucuronidation. In addition, tissue distribution as well as bile excretion studies were performed.

Related Research Articles

<span class="mw-page-title-main">Gilbert's syndrome</span> Medical condition

Gilbert syndrome (GS) is a syndrome in which the liver of affected individuals processes bilirubin more slowly than the majority. Many people never have symptoms. Occasionally jaundice may occur.

Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds.

<span class="mw-page-title-main">Irinotecan</span> Cancer medication

Irinotecan, sold under the brand name Camptosar among others, is an anti-cancer medication used to treat colon cancer and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cisplatin. It is given intravenously.

<span class="mw-page-title-main">Glucuronosyltransferase</span> Class of enzymes

Uridine 5'-diphospho-glucuronosyltransferase is a microsomal glycosyltransferase that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is a glucuronidation reaction.

<span class="mw-page-title-main">Thiopurine methyltransferase</span>

Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme that in humans is encoded by the TPMT gene. A pseudogene for this locus is located on chromosome 18q.

<span class="mw-page-title-main">UDP glucuronosyltransferase 1 family, polypeptide A1</span> Enzyme found in humans

UDP-glucuronosyltransferase 1-1 also known as UGT-1A is an enzyme that in humans is encoded by the UGT1A1 gene.

<span class="mw-page-title-main">UGT2B7</span> Protein-coding gene in the species Homo sapiens

UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. In humans, UDP-Glucuronosyltransferase-2B7 is encoded by the UGT2B7 gene.

<span class="mw-page-title-main">SN-38</span> Chemical compound

SN-38 is an antineoplastic drug. It is the active metabolite of irinotecan but has 1000 times more activity than irinotecan itself. In vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies from 2- to 2000-fold.

<span class="mw-page-title-main">UGT1A6</span> Protein-coding gene in the species Homo sapiens

UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the UGT1A6 gene.

<span class="mw-page-title-main">UGT1A10</span> Protein-coding gene in the species Homo sapiens

UDP-glucuronosyltransferase 1-10 is an enzyme that in humans is encoded by the UGT1A10 gene.

<span class="mw-page-title-main">UGT2B15</span> Protein-coding gene in the species Homo sapiens

UDP-glucuronosyltransferase 2B15 is an enzyme that in humans is encoded by the UGT2B15 gene.

<span class="mw-page-title-main">UGT1A3</span> Protein-coding gene in the species Homo sapiens

UDP-glucuronosyltransferase 1-3 is an enzyme that in humans is encoded by the UGT1A3 gene.

<span class="mw-page-title-main">UGT1A4</span> Enzyme and protein-coding gene in humans

UDP-glucuronosyltransferase 1-4 is an enzyme that in humans is encoded by the UGT1A4 gene.

<span class="mw-page-title-main">UGT2B4</span> Protein-coding gene in the species Homo sapiens

UDP glucuronosyltransferase 2 family, polypeptide B4, also known as UGT2B4, is an enzyme that in humans is encoded by the UGT2B4 gene.

<span class="mw-page-title-main">UGT2B17</span> Protein-coding gene in the species Homo sapiens

UDP-glucuronosyltransferase 2B17 is an enzyme that in humans is encoded by the UGT2B17 gene.

UDP glucuronosyltransferase 1 family, polypeptide A cluster (UGT1A) is a human gene locus which includes several UDP glucuronosyltransferases.

<span class="mw-page-title-main">UGT1A5</span> Protein-coding gene in the species Homo sapiens

UDP-glucuronosyltransferase 1-5 is an enzyme that in humans is encoded by the UGT1A5 gene.

<span class="mw-page-title-main">UGT1A8</span> Protein-coding gene in the species Homo sapiens

UDP-glucuronosyltransferase 1-8 is an enzyme that in humans is encoded by the UGT1A8 gene.

<span class="mw-page-title-main">UGT2A1</span> Protein-coding gene in the species Homo sapiens

UDP glucuronosyltransferase 2 family, polypeptide B1, also known as UGT2B1, is an enzyme that in humans is encoded by the UGT2B1 gene.

<i>UGT1A7</i> (gene) Protein-coding gene in the species Homo sapiens

UDP glucuronosyltransferase 1 family, polypeptide A7 is a protein that in humans is encoded by the UGT1A7 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000241119 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000090165 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Wooster R, Sutherland L, Ebner T, Clarke D, Da Cruz e Silva O, Burchell B (September 1991). "Cloning and stable expression of a new member of the human liver phenol/bilirubin: UDP-glucuronosyltransferase cDNA family". Biochem. J. 278 (2): 465–9. doi:10.1042/bj2780465. PMC   1151367 . PMID   1910331.
  6. Mackenzie PI, Owens IS, Burchell B, Bock KW, Bairoch A, Belanger A, Fournel-Gigleux S, Green M, Hum DW, Iyanagi T, Lancet D, Louisot P, Magdalou J, Chowdhury JR, Ritter JK, Schachter H, Tephly TR, Tipton KF, Nebert DW (Oct 1997). "The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence". Pharmacogenetics. 7 (4): 255–69. doi:10.1097/00008571-199708000-00001. PMID   9295054.
  7. Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, Owens IS (Mar 1992). "A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini". J Biol Chem. 267 (5): 3257–61. doi: 10.1016/S0021-9258(19)50724-4 . PMID   1339448.
  8. 1 2 "Entrez Gene: UGT1A9 UDP glucuronosyltransferase 1 family, polypeptide A9".
  9. Thamm S, Willwacher MK, Aspnes GE, Bretschneider T, Brown NF, Buschbom-Helmke S, Fox T, Gargano EM, Grabowski D, Hoenke C, Matera D, Mueck K, Peters S, Reindl S, Riether D, Schmid M, Tautermann CS, Teitelbaum AM, Trünkle C, Veser T, Winter M, Wortmann L (2023). "Discovery of a Novel Potent and Selective HSD17B13 Inhibitor, BI-3231, a Well-Characterized Chemical Probe Available for Open Science". Journal of Medicinal Chemistry. 66 (4): 2832–2850. doi:10.1021/acs.jmedchem.2c01884. PMC   9969402 . PMID   36727857.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.