P22309 (UD11_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
UDP-glucuronosyltransferase 1-1
Short name=UDPGT 1-1
Short name=UGT1*1
Short name=UGT1-01
Short name=UGT1.1
EC=2.4.1.17

Alternative name(s):
Bilirubin-specific UDPGT isozyme 1
Short name=hUG-BR1
UDP-glucuronosyltransferase 1-A
Short name=UGT-1A
Short name=UGT1A
UDP-glucuronosyltransferase 1A1

Gene names

Name:	UGT1A1
Synonyms:	GNT1, UGT1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	533 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.7 Ref.8
Catalytic activity	UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside. Ref.7
Subunit structure	Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGT1A1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX.
Subcellular location	Microsome. Endoplasmic reticulum membrane; Single-pass membrane protein Potential.
Tissue specificity	Expressed in liver. Not expressed in skin or kidney. Ref.2
Polymorphism	Genetic variation in UGT1A1 defines the bilirubin serum levels quantitative trait locus 1 (BILIQTL1) [MIM:601816]. Variation in serum bilirubin is associated with altered cardiovascular disease risk and drug metabolism.
Involvement in disease	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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.22 Ref.23 Ref.27 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. 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. Ref.24 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.23 Ref.29 Ref.30 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.12 Ref.13 Ref.17 Ref.19 Ref.20 Ref.21 Ref.23 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30
Sequence similarities	Belongs to the UDP-glycosyltransferase family.
Biophysicochemical properties	Kinetic parameters: KM=0.26 µM for bilirubin Ref.7 Vmax=1080 pmol/min/mg enzyme with bilirubin as substrate
Sequence caution	The sequence AAA61247.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence AAF03522.2 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Glycosyltransferase Transferase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acute-phase response Inferred from electronic annotation. Source: Compara bilirubin conjugation Traceable author statement Ref.2. Source: ProtInc biphenyl catabolic process Inferred from electronic annotation. Source: Compara cellular response to ethanol Inferred from electronic annotation. Source: Compara cellular response to glucocorticoid stimulus Inferred from electronic annotation. Source: Compara digestion Non-traceable author statement Ref.1. Source: ProtInc drug metabolic process Inferred by curator PubMed 19996319. Source: BHF-UCL estrogen metabolic process Traceable author statement PubMed 8780690. Source: ProtInc flavone metabolic process Inferred from direct assay PubMed 18052087. Source: BHF-UCL flavonoid glucuronidation Inferred from direct assay PubMed 20056724. Source: BHF-UCL heme catabolic process Traceable author statement. Source: Reactome liver development Inferred from electronic annotation. Source: Compara negative regulation of steroid metabolic process Inferred by curator PubMed 19996319. Source: BHF-UCL organ regeneration Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to nutrient Inferred from electronic annotation. Source: Compara response to starvation Inferred from electronic annotation. Source: Compara retinoic acid metabolic process Inferred by curator PubMed 20308471. Source: BHF-UCL xenobiotic glucuronidation Inferred from direct assay PubMed 20056724. Source: BHF-UCL
Cellular_component	cytochrome complex Inferred from electronic annotation. Source: Compara endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	enzyme binding Inferred from direct assay PubMed 20610558. Source: BHF-UCL enzyme inhibitor activity Inferred from direct assay PubMed 19996319. Source: BHF-UCL glucuronosyltransferase activity Inferred from direct assay PubMed 18052087PubMed 19996319PubMed 20056724PubMed 20308471. Source: BHF-UCL retinoic acid binding Inferred from direct assay PubMed 20308471. Source: BHF-UCL steroid binding Inferred from direct assay PubMed 19996319. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 1 isoform produced by alternative splicing. [Select]

Note: A number of isoforms are produced. The different isozymes have a different N-terminal domain and a common C-terminal domain of 245 residues.

Isoform 1 (identifier: P22309-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 533	508	UDP-glucuronosyltransferase 1-1		PRO_0000036000
Regions
	Transmembrane	491 – 507	17	Helical; Potential
Amino acid modifications
	Glycosylation	102	1	N-linked (GlcNAc...) Ref.10
	Glycosylation	295	1	N-linked (GlcNAc...) Potential
	Glycosylation	347	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	15	1	L → R in CN2; mutant protein rapidly degraded by the proteasome owing to its mislocalization in the cell. Ref.8 Ref.19 Ref.23 Ref.28		VAR_019410
	Natural variant	34	1	P → Q in CN2. Ref.29		VAR_026134
	Natural variant	39	1	H → D in CN1. Ref.23		VAR_026135
	Natural variant	71	1	G → R in CN2, GILBS and HBLRTFN; has significant residual bilirubin glucuronidation activity of about 25% to 50% of that of the wild-type protein; displays no change in biluribin affinity. Ref.7 Ref.8 Ref.12 Ref.18 Ref.21 Ref.23 Ref.24 Corresponds to variant rs4148323 [ dbSNP | Ensembl ].		VAR_009504
	Natural variant	83	1	F → L in GILBS; displays less than 10% of wild-type bilirubin glucuronidation activity. Ref.7 Ref.27 Corresponds to variant rs56059937 [ dbSNP | Ensembl ].		VAR_026136
	Natural variant	170	1	Missing in CN1 and CN2; has nearly normal activity at pH 7.6 and is inactive at pH 6.4. Ref.14 Ref.17 Ref.23 Ref.29		VAR_007695
	Natural variant	171	1	Missing in CN2. Ref.30		VAR_064955
	Natural variant	175	1	L → Q in CN2; has low residual bilirubin glucuronidation activity of about 4.6% of that of the wild-type protein. Ref.8 Ref.17 Ref.23 Ref.25		VAR_019411
	Natural variant	177	1	C → R in CN1. Ref.17 Ref.23		VAR_007697
	Natural variant	191	1	S → F in CN2; has low residual bilirubin glucuronidation activity of about 5.3% of that of the wild-type protein. Ref.8		VAR_064956
	Natural variant	209	1	R → W in CN2; has low residual bilirubin glucuronidation activity of about 2.9% of that of the wild-type protein. Ref.8 Ref.17 Ref.21 Ref.23 Ref.29		VAR_007698
	Natural variant	225	1	V → G in CN2. Ref.23 Ref.29 Corresponds to variant rs35003977 [ dbSNP | Ensembl ].		VAR_026137
	Natural variant	229	1	P → Q in CN2 and GILBS; displays 2-fold decrease in biluribin affinity and 61% of wild-type bilirubin glucuronidation activity. Ref.7 Ref.18 Ref.21 Ref.23		VAR_009505
	Natural variant	276	1	G → R in CN1. Ref.17 Ref.23		VAR_007699
	Natural variant	279	1	N → Y in CN2. Ref.30		VAR_064957
	Natural variant	291	1	E → V in CN1. Ref.23		VAR_026138
	Natural variant	292	1	A → V in CN1. Ref.15		VAR_007700
	Natural variant	294	1	I → T in GILBS and CN2; 40-55% normal activity; normal Km for bilirubin; when homozygous far less repressive and generates the mild Gilbert phenotype. Ref.20 Ref.23		VAR_026139
	Natural variant	308	1	G → E in CN1; no enzyme activity. Ref.15 Ref.16 Ref.23		VAR_007701
	Natural variant	331	1	Q → R in CN2; has no residual bilirubin glucuronidation activity. Ref.8 Ref.13 Ref.23		VAR_007702
	Natural variant	336	1	R → L in CN1 and CN2. Ref.29		VAR_026140
	Natural variant	336	1	R → Q in CN1. Ref.29		VAR_026141
	Natural variant	336	1	R → W in CN2; has very low residual bilirubin glucuronidation activity of about 0.4% of that of the wild-type protein. Ref.8 Ref.23 Ref.29		VAR_026142
	Natural variant	354	1	W → R in CN2. Ref.29 Ref.30		VAR_026143
	Natural variant	357	1	Q → R in CN1. Ref.15 Ref.23 Ref.29		VAR_007703
	Natural variant	367	1	R → G in GILBS. Ref.18 Ref.23 Corresponds to variant rs55750087 [ dbSNP | Ensembl ].		VAR_012283
	Natural variant	368	1	A → T in CN1. Ref.15 Ref.23		VAR_007704
	Natural variant	370	1	I → V in CN2. Ref.30		VAR_064958
	Natural variant	375	1	S → F in CN1; no enzyme activity. Ref.11 Ref.16 Ref.17 Ref.23 Ref.29		VAR_007705
	Natural variant	376	1	H → R in CN1 and CN2.		VAR_026144
	Natural variant	377	1	G → V in CN1 and CN2. Ref.29		VAR_026145
	Natural variant	381	1	S → R in CN1. Ref.15 Ref.23		VAR_007706
	Natural variant	387	1	P → H in CN2; has no residual bilirubin glucuronidation activity. Ref.8		VAR_064959
	Natural variant	387	1	P → S in CN1. Ref.23 Ref.29		VAR_026146
	Natural variant	395	1	G → V in CN1; has no residual bilirubin glucuronidation activity. Ref.8 Ref.29 Ref.30		VAR_026147
	Natural variant	400	1	N → D in CN2. Ref.26 Corresponds to variant rs28934877 [ dbSNP | Ensembl ].		VAR_019412
	Natural variant	401	1	A → P in CN1. Ref.15 Ref.23		VAR_007707
	Natural variant	402	1	K → T in CN1; has no residual bilirubin glucuronidation activity; N-glycosylation does take place at this new additional site. Ref.8		VAR_064960
	Natural variant	403	1	R → C in CN2. Ref.29		VAR_026148
	Natural variant	428	1	K → E in CN1. Ref.15 Ref.23		VAR_007708
	Natural variant	443	1	L → P in CN2; has no residual bilirubin glucuronidation activity. Ref.8 Ref.30		VAR_064961
	Natural variant	461	1	W → R in CN1 and CN2. Ref.29 Ref.30		VAR_026149
	Natural variant	478	1	A → D in CN2. Ref.29		VAR_026150
	Natural variant	486	1	Y → D in CN2, GILBS and HBLRTFN; displays less than 10% of wild-type bilirubin glucuronidation activity. Ref.7 Ref.8 Ref.12 Ref.21 Ref.22 Ref.23 Ref.24		VAR_007709
	Natural variant	511	1	A → P. Corresponds to variant rs1042709 [ dbSNP | Ensembl ].		VAR_025355

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1991. Version 1. Checksum: 19C90231AD0EB547	FASTA	533	59,591
	10 20 30 40 50 60 MAVESQGGRP LVLGLLLCVL GPVVSHAGKI LLIPVDGSHW LSMLGAIQQL QQRGHEIVVL 70 80 90 100 110 120 APDASLYIRD GAFYTLKTYP VPFQREDVKE SFVSLGHNVF ENDSFLQRVI KTYKKIKKDS 130 140 150 160 170 180 AMLLSGCSHL LHNKELMASL AESSFDVMLT DPFLPCSPIV AQYLSLPTVF FLHALPCSLE 190 200 210 220 230 240 FEATQCPNPF SYVPRPLSSH SDHMTFLQRV KNMLIAFSQN FLCDVVYSPY ATLASEFLQR 250 260 270 280 290 300 EVTVQDLLSS ASVWLFRSDF VKDYPRPIMP NMVFVGGINC LHQNPLSQEF EAYINASGEH 310 320 330 340 350 360 GIVVFSLGSM VSEIPEKKAM AIADALGKIP QTVLWRYTGT RPSNLANNTI LVKWLPQNDL 370 380 390 400 410 420 LGHPMTRAFI THAGSHGVYE SICNGVPMVM MPLFGDQMDN AKRMETKGAG VTLNVLEMTS 430 440 450 460 470 480 EDLENALKAV INDKSYKENI MRLSSLHKDR PVEPLDLAVF WVEFVMRHKG APHLRPAAHD 490 500 510 520 530 LTWYQYHSLD VIGFLLAVVL TVAFITFKCC AYGYRKCLGK KGRVKKAHKS KTH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells." Ritter J.K., Crawford J.M., Owens I.S. J. Biol. Chem. 266:1043-1047(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini." Ritter J.K., Chen F., Sheen Y.Y., Tran H.M., Kimura S., Yeatman M.T., Owens I.S. J. Biol. Chem. 267:3257-3261(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[3]	"Thirteen UDP-glucuronosyltransferase genes are encoded at the human UGT1 gene complex locus." Gong Q.H., Cho J.W., Huang T., Potter C., Gholami N., Basu N.K., Kubota S., Carvalho S., Pennington M.W., Owens I.S., Popescu N.C. Pharmacogenetics 11:357-368(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Analysis of the promoter of human bilirubin UDP-glucuronosyltransferase gene (UGT1*1) in relevance to Gilbert's syndrome." Ueyama H., Koiwai O., Soeda Y., Sato H., Satoh Y., Ohkubo I., Doida Y. Hepatol. Res. 9:152-163(1997) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50.
[6]	"A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins." Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M. Mol. Biol. Cell 13:4456-4469(2002) [PubMed] [Europe PMC] [Abstract] Cited for: COMPONENT OF A CHAPERONE COMPLEX.
[7]	"Influence of mutations associated with Gilbert and Crigler-Najjar type II syndromes on the glucuronidation kinetics of bilirubin and other UDP-glucuronosyltransferase 1A substrates." Udomuksorn W., Elliot D.J., Lewis B.C., Mackenzie P.I., Yoovathaworn K., Miners J.O. Pharmacogenet. Genomics 17:1017-1029(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, KINETIC PARAMETERS, SUBSTRATE SPECIFICITY, CHARACTERIZATION OF VARIANTS CN2 ARG-71; LEU-83; GLN-229 AND ASP-486.
[8]	"Crigler-Najjar syndrome in The Netherlands: identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutants." Sneitz N., Bakker C.T., de Knegt R.J., Halley D.J., Finel M., Bosma P.J. Hum. Mutat. 31:52-59(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBSTRATE SPECIFICITY, VARIANT CN1 THR-402, VARIANTS CN2 ARG-15; ARG-71; PHE-191; TRP-209; TRP-336; HIS-387; PRO-443 AND ASP-486, CHARACTERIZATION OF VARIANT CN1 THR-402, CHARACTERIZATION OF VARIANTS CN2 ARG-71; GLN-175; PHE-191; TRP-209; ARG-331; TRP-336; HIS-387; VAL-395 AND PRO-443.
[9]	"Genome-wide association meta-analysis for total serum bilirubin levels." Johnson A.D., Kavousi M., Smith A.V., Chen M.H., Dehghan A., Aspelund T., Lin J.P., van Duijn C.M., Harris T.B., Cupples L.A., Uitterlinden A.G., Launer L., Hofman A., Rivadeneira F., Stricker B., Yang Q., O'Donnell C.J., Gudnason V., Witteman J.C. Hum. Mol. Genet. 18:2700-2710(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN BILIQTL1.
[10]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-102, MASS SPECTROMETRY. Tissue: Liver.
[11]	"Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I." Bosma P.J., Chowdhury J.R., Huang T.-J., Lahiri P., Elferink R.P.J.O., van Es H.H.G., Lederstein M., Whitington P.F., Jansen P.L.M., Chowdhury N.R. FASEB J. 6:2859-2863(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CN1 PHE-375.
[12]	"Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II." Aono S., Yamada Y., Keino H., Hanada N., Nakagawa T., Sasaoka Y., Yazawa T., Sato H., Koiwai O. Biochem. Biophys. Res. Commun. 197:1239-1244(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CN2 ARG-71 AND ASP-486.
[13]	"Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2." Moghrabi N., Clarke D.J., Boxer M., Burchell B. Genomics 18:171-173(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CN2 ARG-331.
[14]	"A phenylalanine codon deletion at the UGT1 gene complex locus of a Crigler-Najjar type I patient generates a pH-sensitive bilirubin UDP-glucuronosyltransferase." Ritter J.K., Yeatman M.T., Kaiser C., Gridelli B., Owens I.S. J. Biol. Chem. 268:23573-23579(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CN1 PHE-170 DEL.
[15]	"Genetic heterogeneity of Crigler-Najjar syndrome type I: a study of 14 cases." Labrune P., Myara A., Hadchouel M., Ronchi F., Bernard O., Trivin F., Roy Chowdhury N., Roy Chowdhury J., Munnich A., Odievre M. Hum. Genet. 94:693-697(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CN1 VAL-292; GLU-308; ARG-357; THR-368; ARG-381; PRO-401 AND GLU-428.
[16]	"Identification of two single base substitutions in the UGT1 gene locus which abolish bilirubin uridine diphosphate glucuronosyltransferase activity in vitro." Erps L.T., Ritter J.K., Hersh J.H., Blossom D., Martin N.C., Owens I.S. J. Clin. Invest. 93:564-570(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CN1 GLU-308 AND PHE-375, CHARACTERIZATION OF VARIANTS CN1 GLU-308 AND PHE-375.
[17]	"Discrimination between Crigler-Najjar type I and II by expression of mutant bilirubin uridine diphosphate-glucuronosyltransferase." Seppen J., Bosma P.J., Goldhoorn B.G., Bakker C.T.M., Roy Chowdhury J., Roy Chowdhury N., Jansen P.L.M., Oude Elferink R.P.J. J. Clin. Invest. 94:2385-2391(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CN1 PHE-170 DEL; ARG-177; ARG-276 AND PHE-375, VARIANTS CN2 GLN-175 AND TRP-209.
[18]	"Analysis of genes for bilirubin UDP-glucuronosyltransferase in Gilbert's syndrome." Aono S., Adachi Y., Uyama E., Yamada Y., Keino H., Nanno T., Koiwai O., Sato H. Lancet 345:958-959(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GILBS ARG-71; GLN-229 AND GLY-367. Tissue: Liver and Peripheral blood leukocyte.
[19]	"A mutation which disrupts the hydrophobic core of the signal peptide of bilirubin UDP-glucuronosyltransferase, an endoplasmic reticulum membrane protein, causes Crigler-Najjar type II." Seppen J., Steenken E., Lindhout D., Bosma P.J., Oude Elferink R.P.J. FEBS Lett. 390:294-298(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CN2 ARG-15, CHARACTERIZATION OF VARIANT CN2 ARG-15.
[20]	"Coding defect and a TATA box mutation at the bilirubin UDP-glucuronosyltransferase gene cause Crigler-Najjar type I disease." Ciotti M., Chen F., Rubaltelli F.F., Owens I.S. Biochim. Biophys. Acta 1407:40-50(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CN2 THR-294, CHARACTERIZATION OF VARIANT CN2 THR-294.
[21]	"Analysis of bilirubin uridine 5'-diphosphate (UDP)-glucuronosyltransferase gene mutations in seven patients with Crigler-Najjar syndrome type II." Yamamoto K., Soeda Y., Kamisako T., Hosaka H., Fukano M., Sato H., Fujiyama Y., Dachi Y., Satoh Y., Bamba T. J. Hum. Genet. 43:111-114(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CN2 ARG-71; TRP-209; GLN-229 AND ASP-486.
[22]	"Gilbert syndrome caused by a homozygous missense mutation (Tyr486Asp) of bilirubin UDP-glucuronosyltransferase gene." Maruo Y., Sato H., Yamano T., Doida Y., Shimada M. J. Pediatr. 132:1045-1047(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GILBS ASP-486.
[23]	"Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype." Kadakol A., Ghosh S.S., Sappal B.S., Sharma G., Chowdhury J.R., Chowdhury N.R. Hum. Mutat. 16:297-306(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CN1 ASP-39; PHE-170 DEL; ARG-177; ARG-276; VAL-291; GLU-308; TRP-336; ARG-357; THR-368; PHE-375; ARG-381; SER-387; PRO-401 AND GLU-428, VARIANTS CN2 ARG-15; GLN-175; TRP-209; GLY-225 AND ARG-331, VARIANTS GILBS ARG-71; GLN-229; THR-294; GLY-367 AND ASP-486.
[24]	"Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate-glucuronosyltransferase gene." Maruo Y., Nishizawa K., Sato H., Sawa H., Shimada M. Pediatrics 106:E59-E59(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HBLRTFN ARG-71 AND ASP-486.
[25]	"Interaction of coding region mutations and the Gilbert-type promoter abnormality of the UGT1A1 gene causes moderate degrees of unconjugated hyperbilirubinaemia and may lead to neonatal kernicterus." Kadakol A., Sappal B.S., Ghosh S.S., Lowenheim M., Chowdhury A., Chowdhury S., Santra A., Arias I.M., Chowdhury J.R., Chowdhury N.R. J. Med. Genet. 38:244-249(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CN2 GLN-175.
[26]	"Association of a homozygous (TA)8 promoter polymorphism and a N400D mutation of UGT1A1 in a child with Crigler-Najjar type II syndrome." Labrune P., Myara A., Chalas J., Le Bihan B., Capel L., Francoual J. Hum. Mutat. 20:399-401(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CN2 ASP-400.
[27]	"Novel missense mutation of the UGT1A1 gene in Thai siblings with Gilbert's syndrome." Sutomo R., Laosombat V., Sadewa A.H., Yokoyama N., Nakamura H., Matsuo M., Nishio H. Pediatr. Int. 44:427-432(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GILBS LEU-83.
[28]	"Rapid proteasomal degradation of translocation-deficient UDP-glucuronosyltransferase 1A1 proteins in patients with Crigler-Najjar type II." Ohnishi A., Emi Y. Biochem. Biophys. Res. Commun. 310:735-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT CN2 ARG-15.
[29]	"Spectrum of UGT1A1 mutations in Crigler-Najjar (CN) syndrome patients: identification of twelve novel alleles and genotype-phenotype correlation." Servedio V., d'Apolito M., Maiorano N., Minuti B., Torricelli F., Ronchi F., Zancan L., Perrotta S., Vajro P., Boschetto L., Iolascon A. Hum. Mutat. 25:325-325(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CN1 GLN-336; ARG-357; PHE-375; SER-387 AND VAL-395, VARIANTS CN2 GLN-34; PHE-170 DEL; TRP-209; GLY-225; LEU-336; TRP-336; ARG-354; CYS-403 AND ASP-478, VARIANTS CN1/CN2 VAL-377 AND ARG-461.
[30]	"Seven novel mutations of the UGT1A1 gene in patients with unconjugated hyperbilirubinemia." D'Apolito M., Marrone A., Servedio V., Vajro P., De Falco L., Iolascon A. Haematologica 92:133-134(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CN1 PHE-171 DEL, VARIANTS CN2 TYR-279; ARG-354; VAL-370; VAL-395; PRO-443 AND ARG-461.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Glucuronosyltransferase entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	M57899 mRNA. Translation: AAA63195.1. M84124, M84122, M84123 Genomic DNA. Translation: AAA61247.1. Sequence problems. M84125 Genomic DNA. Translation: AAA61248.1. AF297093 Genomic DNA. Translation: AAG30424.1. AC006985 Genomic DNA. Translation: AAF03522.2. Sequence problems. D87674 Genomic DNA. Translation: BAA25600.1.
IPI	IPI00434346.
PIR	A39092.
RefSeq	NP_000454.1. NM_000463.2.
UniGene	Hs.554822.
3D structure databases
ProteinModelPortal	P22309.
ModBase	Search...
Protein-protein interaction databases
IntAct	P22309. 1 interaction.
STRING	9606.ENSP00000304845.
Protein family/group databases
CAZy	GT1. Glycosyltransferase Family 1.
PTM databases
PhosphoSite	P22309.
Polymorphism databases
DMDM	136729.
Proteomic databases
PaxDb	P22309.
PeptideAtlas	P22309.
PRIDE	P22309.
Protocols and materials databases
DNASU	54658.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000305208; ENSP00000304845; ENSG00000241635.
GeneID	54658.
KEGG	hsa:54658.
UCSC	uc002vvb.3. human.
Organism-specific databases
CTD	54658.
GeneCards	GC02P234668.
HGNC	HGNC:12530. UGT1A1.
MIM	143500. phenotype. 191740. gene. 218800. phenotype. 237900. phenotype. 601816. phenotype. 606785. phenotype.
neXtProt	NX_P22309.
Orphanet	79234. Crigler-Najjar syndrome type 1. 79235. Crigler-Najjar syndrome type 2. 357. Gilbert syndrome. 240885. Irinotecan toxicity. 240905. Raltegravir toxicity. 240973. Susceptibility to adverse reaction due to irinotecan treatment. 241017. Susceptibility to icterus due to raltegravir treatment. 2312. Transient familial neonatal hyperbilirubinemia.
PharmGKB	PA420.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1819.
HOGENOM	HOG000220832.
HOVERGEN	HBG004033.
KO	K00699.
OMA	ESHFRRM.
OrthoDB	EOG45B1FF.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
SABIO-RK	P22309.
Gene expression databases
ArrayExpress	P22309.
Bgee	P22309.
CleanEx	HS_UGT1A1.
Genevestigator	P22309.
GermOnline	ENSG00000167165. Homo sapiens.
Family and domain databases
InterPro	IPR002213. UDP_glucos_trans. [Graphical view]
PANTHER	PTHR11926. PTHR11926. 1 hit.
Pfam	PF00201. UDPGT. 1 hit. [Graphical view]
PROSITE	PS00375. UDPGT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P22309.
ChEMBL	CHEMBL1287617.
DrugBank	DB01048. Abacavir. DB00173. Adenine. DB00586. Diclofenac. DB00783. Estradiol. DB00973. Ezetimibe. DB00762. Irinotecan. DB00688. Mycophenolate mofetil. DB01024. Mycophenolic acid. DB00818. Propofol. DB01045. Rifampin. DB00197. Troglitazone.
GenomeRNAi	54658.
NextBio	57188.
SOURCE	Search...

Entry information

Entry name

UD11_HUMAN

Accession

Primary (citable) accession number: P22309

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1991
Last modified:	May 1, 2013
This is version 149 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.