InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: UGT1A1

Summary

InnateDB Protein

IDBP-83572.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

UGT1A1

Protein Name

UDP glucuronosyltransferase 1 family, polypeptide A1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000304845

InnateDB Gene

IDBG-407489 (UGT1A1)

Protein Structure

UniProt Annotation

Function

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX- alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4- methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1. {ECO:0000269PubMed:18004206, ECO:0000269PubMed:19545173, ECO:0000269PubMed:19830808}.

Subcellular Localization

Isoform 1: Microsome. Endoplasmic reticulum membrane {ECO:0000305}; Single-pass membrane protein {ECO:0000305}.Isoform 2: Endoplasmic reticulum.

Disease Associations

Gilbert syndrome (GILBS) [MIM:143500]: Occurs as a consequence of reduced bilirubin transferase activity and is often detected in young adults with vague non-specific complaints. {ECO:0000269PubMed:11013440, ECO:0000269PubMed:12139570, ECO:0000269PubMed:7715297, ECO:0000269PubMed:9627603}. Note=The disease is caused by mutations affecting the gene represented in this entry.Transient familial neonatal hyperbilirubinemia (HBLRTFN) [MIM:237900]: A condition characterized by excessive concentration of bilirubin in the blood, which may lead to jaundice. Breast milk jaundice is a common problem in nursing infants. {ECO:0000269PubMed:11061796}. Note=The disease may be caused by mutations affecting the gene represented in this entry. The defect has been ascribed to various breast milk substances, but the component or combination of components that is responsible remains unclear. Defects of UGT1A1 are an underlying cause of the prolonged unconjugated hyperbilirubinemia associated with breast milk. One or more components in the milk may trigger the jaundice in infants who have such mutations. Mutations are identical to those detected in patients with Gilbert syndrome, a risk factor of neonatal non-physiologic hyperbilirubinemia and a genetic factor in fasting hyperbilirubinemia.Crigler-Najjar syndrome 1 (CN1) [MIM:218800]: Patients have severe hyperbilirubinemia and usually die of kernicterus (bilirubin accumulation in the basal ganglia and brainstem nuclei) within the first year of life. CN1 inheritance is autosomal recessive. {ECO:0000269PubMed:11013440, ECO:0000269PubMed:15712364, ECO:0000269PubMed:1634050, ECO:0000269PubMed:17229650, ECO:0000269PubMed:19830808, ECO:0000269PubMed:7906695, ECO:0000269PubMed:7989045, ECO:0000269PubMed:7989595, ECO:0000269PubMed:8226884}. Note=The disease is caused by mutations affecting the gene represented in this entry.Crigler-Najjar syndrome 2 (CN2) [MIM:606785]: Patients have less severe hyperbilirubinemia and usually survive into adulthood without neurologic damage. Phenobarbital, which induces the partially deficient glucuronyl transferase, can diminish the jaundice. CN2 inheritance is autosomal dominant. {ECO:0000269PubMed:11013440, ECO:0000269PubMed:11370628, ECO:0000269PubMed:12402338, ECO:0000269PubMed:15712364, ECO:0000269PubMed:17229650, ECO:0000269PubMed:19830808, ECO:0000269PubMed:7989595, ECO:0000269PubMed:8276413, ECO:0000269PubMed:8280139, ECO:0000269PubMed:8706880, ECO:0000269PubMed:9621515, ECO:0000269PubMed:9639672}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Isoform 1 and isoform 2 are expressed in liver, colon and small intestine. Isoform 2 but not isoform 1 is expressed in kidney. Isoform 1 and isoform 2 are not expressed in esophagus. Not expressed in skin. {ECO:0000269PubMed:1339448, ECO:0000269PubMed:17187418, ECO:0000269PubMed:18004212}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.

Experimentally validated
Total	6 [view]
Protein-Protein	4 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001972	retinoic acid binding
GO:0004857	enzyme inhibitor activity
GO:0005496	steroid binding
GO:0015020	glucuronosyltransferase activity
GO:0016758	transferase activity, transferring hexosyl groups
GO:0019899	enzyme binding
GO:0030246	carbohydrate binding
GO:0042803	protein homodimerization activity
GO:0046982	protein heterodimerization activity

Biological Process

GO:0001889	liver development
GO:0005975	carbohydrate metabolic process
GO:0006778	porphyrin-containing compound metabolic process
GO:0006789	bilirubin conjugation
GO:0006805	xenobiotic metabolic process
GO:0006953	acute-phase response
GO:0007584	response to nutrient
GO:0007586	digestion
GO:0008152	metabolic process
GO:0008202	steroid metabolic process
GO:0008210	estrogen metabolic process
GO:0010033	response to organic substance
GO:0014070	response to organic cyclic compound
GO:0017144	drug metabolic process
GO:0030259	lipid glycosylation
GO:0031100	organ regeneration
GO:0032496	response to lipopolysaccharide
GO:0032870	cellular response to hormone stimulus
GO:0042167	heme catabolic process
GO:0042493	response to drug
GO:0042573	retinoic acid metabolic process
GO:0042594	response to starvation
GO:0043086	negative regulation of catalytic activity
GO:0044281	small molecule metabolic process
GO:0045471	response to ethanol
GO:0045939	negative regulation of steroid metabolic process
GO:0046483	heterocycle metabolic process
GO:0048545	response to steroid hormone
GO:0051384	response to glucocorticoid
GO:0051552	flavone metabolic process
GO:0052695	cellular glucuronidation
GO:0052696	flavonoid glucuronidation
GO:0052697	xenobiotic glucuronidation
GO:0070980	biphenyl catabolic process
GO:0071361	cellular response to ethanol
GO:0071385	cellular response to glucocorticoid stimulus
GO:2001030	negative regulation of cellular glucuronidation

Cellular Component

GO:0005783	endoplasmic reticulum
GO:0005789	endoplasmic reticulum membrane
GO:0005887	integral component of plasma membrane
GO:0043231	intracellular membrane-bounded organelle
GO:0070069	cytochrome complex