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P19224 (UD16_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
UDP-glucuronosyltransferase 1-6

Short name=UDPGT 1-6
Short name=UGT1*6
Short name=UGT1-06
Short name=UGT1.6
EC=2.4.1.17
Alternative name(s):
Phenol-metabolizing UDP-glucuronosyltransferase
UDP-glucuronosyltransferase 1-F
Short name=UGT-1F
Short name=UGT1F
UDP-glucuronosyltransferase 1A6
Gene names
Name:UGT1A6
Synonyms:GNT1, UGT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length532 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 hasspecificity for phenols. Isoform 3 lacks transferase activity but acts as a negative regulator of isoform 1 By similarity.

Catalytic activity

UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside.

Subunit structure

Isoform 1 interacts with isoform 3/i2suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 3. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A7, UGT1A8, UGT1A9 and UGT1A10. Ref.9

Subcellular location

Microsome. Endoplasmic reticulum membrane; Single-pass membrane protein Potential.

Tissue specificity

Expressed in skin. Isoforms 1 and 3 are expressed in kidney and liver. Isoform 1 but not isoform 2 is expressed in colon, esophagus and small intestine. Ref.1 Ref.8

Polymorphism

Polymorphisms in the UGT1A6 gene define four common haplotypes: UGT1A6*1, UGT1A6*2, UGT1A6*3 and UGT1A6*4. Liver tissue samples that were homozygous for UGT1A6*2 exhibited a high rate of glucuronidation relative to tissues with other genotypes. Biochemical kinetic studies indicate that the UGT1A6*2 allozyme, expressed homozygously, had almost two-fold greater activity toward p-nitrophenol than UGT1A6*1 and when expressed heterozygously (UGT1A6*1/*2) it is associated with low enzyme activity. Common genetic variation in UGT1A6 confers functionally significant differences in biochemical phenotype. This genetic variation might impact clinical efficacy or toxicity of drugs metabolized by UGT1A6.

Miscellaneous

The gene is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.

Sequence similarities

Belongs to the UDP-glycosyltransferase family.

Sequence caution

The sequence BM924331 differs from that shown. Reason: Erroneous termination at position 420. Translated as Glu.

The sequence BM924331 differs from that shown. Reason: Frameshift at positions 451 and 463.

The sequence BM924331 differs from that shown. Reason: Probable cloning artifact.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P19224-1)

Also known as: i1;

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.
Isoform 2 (identifier: P19224-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-267: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P19224-3)

Also known as: i2; UGT1A6s;

The sequence of this isoform differs from the canonical sequence as follows:
     434-532: SYKENIMRLS...VKKAHKSKTH → RKKQQSGRQM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 532506UDP-glucuronosyltransferase 1-6
PRO_0000036005

Regions

Transmembrane490 – 50617Helical; Potential

Amino acid modifications

Glycosylation2941N-linked (GlcNAc...) Potential
Glycosylation3461N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 267267Missing in isoform 2.
VSP_045779
Alternative sequence434 – 53299SYKEN…KSKTH → RKKQQSGRQM in isoform 3.
VSP_053962
Natural variant71S → A in allele UGT1A6*2, allele UGT1A6*3 and allele UGT1A6*4. Ref.11
Corresponds to variant rs6759892 [ dbSNP | Ensembl ].
VAR_024685
Natural variant701S → Y. Ref.1
Corresponds to variant rs1042708 [ dbSNP | Ensembl ].
VAR_026628
Natural variant1811T → A in allele UGT1A6*2. Ref.4 Ref.10 Ref.11 Ref.12
Corresponds to variant rs2070959 [ dbSNP | Ensembl ].
VAR_014784
Natural variant1841R → S in allele UGT1A6*2 and allele UGT1A6*4. Ref.4 Ref.10 Ref.11 Ref.12
Corresponds to variant rs1105879 [ dbSNP | Ensembl ].
VAR_015559
Natural variant5101A → P. Ref.1
Corresponds to variant rs1042709 [ dbSNP | Ensembl ].
VAR_026629

Experimental info

Sequence conflict2311E → K in AAA61251. Ref.1
Sequence conflict247 – 2493YQK → SE in AAA61251. Ref.1
Sequence conflict3281I → N in AAA61251. Ref.1
Sequence conflict4191S → F in BM924331. Ref.6
Sequence conflict4461H → S in BM924331. Ref.6
Sequence conflict4681K → Q in BM924331. Ref.6
Sequence conflict476 – 4772AA → GS in BM924331. Ref.6
Sequence conflict5141R → P in AAA61251. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (i1) [UniParc].

Last modified April 11, 2003. Version 2.
Checksum: 4A9EA6A88CBC3136

FASTA53260,751
        10         20         30         40         50         60 
MACLLRSFQR ISAGVFFLAL WGMVVGDKLL VVPQDGSHWL SMKDIVEVLS DRGHEIVVVV 

        70         80         90        100        110        120 
PEVNLLLKES KYYTRKIYPV PYDQEELKNR YQSFGNNHFA ERSFLTAPQT EYRNNMIVIG 

       130        140        150        160        170        180 
LYFINCQSLL QDRDTLNFFK ESKFDALFTD PALPCGVILA EYLGLPSVYL FRGFPCSLEH 

       190        200        210        220        230        240 
TFSRSPDPVS YIPRCYTKFS DHMTFSQRVA NFLVNLLEPY LFYCLFSKYE ELASAVLKRD 

       250        260        270        280        290        300 
VDIITLYQKV SVWLLRYDFV LEYPRPVMPN MVFIGGINCK KRKDLSQEFE AYINASGEHG 

       310        320        330        340        350        360 
IVVFSLGSMV SEIPEKKAMA IADALGKIPQ TVLWRYTGTR PSNLANNTIL VKWLPQNDLL 

       370        380        390        400        410        420 
GHPMTRAFIT HAGSHGVYES ICNGVPMVMM PLFGDQMDNA KRMETKGAGV TLNVLEMTSE 

       430        440        450        460        470        480 
DLENALKAVI NDKSYKENIM RLSSLHKDRP VEPLDLAVFW VEFVMRHKGA PHLRPAAHDL 

       490        500        510        520        530 
TWYQYHSLDV IGFLLAVVLT VAFITFKCCA YGYRKCLGKK GRVKKAHKSK TH 

« Hide

Isoform 2 [UniParc].

Checksum: C0DEE8F8EC498CFD
Show »

FASTA26529,647
Isoform 3 (i2) (UGT1A6s) [UniParc].

Checksum: D49A8F5D16A09EDD
Show »

FASTA44350,528

References

« Hide 'large scale' references
[1]"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, VARIANTS TYR-70 AND PRO-510.
[2]"Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells."
Harding D., Fournel-Gigleux S., Jackson M.R., Burchell B.
Proc. Natl. Acad. Sci. U.S.A. 85:8381-8385(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[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]Guillemette C., Levesque E., Girard H., Bernard O.
Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANTS ALA-181 AND SER-184.
[5]"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. expand/collapse author list , 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].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-488 (ISOFORM 2).
[7]"Aryl hydrocarbon receptor-inducible or constitutive expression of human UDP glucuronosyltransferase UGT1A6."
Muenzel P.A., Lehmkoester T., Brueck M., Ritter J.K., Bock K.W.
Arch. Biochem. Biophys. 350:72-78(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
[8]"Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activity."
Girard H., Levesque E., Bellemare J., Journault K., Caillier B., Guillemette C.
Pharmacogenet. Genomics 17:1077-1089(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[9]"Alternatively spliced products of the UGT1A gene interact with the enzymatically active proteins to inhibit glucuronosyltransferase activity in vitro."
Bellemare J., Rouleau M., Girard H., Harvey M., Guillemette C.
Drug Metab. Dispos. 38:1785-1789(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[10]"Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications."
Ciotti M., Marrone A., Potter C., Owens I.S.
Pharmacogenetics 7:485-495(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-181 AND SER-184.
[11]"Human UGT1A6 pharmacogenetics: identification of a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissue and in cultured cells."
Nagar S., Zalatoris J.J., Blanchard R.L.
Pharmacogenetics 14:487-499(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-7; ALA-181 AND SER-184.
[12]"Analysis of inherited genetic variations at the UGT1 locus in the French-Canadian population."
Menard V., Girard H., Harvey M., Perusse L., Guillemette C.
Hum. Mutat. 30:677-687(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ALA-181 AND SER-184.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M84130 Genomic DNA. Translation: AAC41717.1.
M84124, M84122, M84123 Genomic DNA. Translation: AAA61247.1. Sequence problems.
J04093 mRNA. Translation: AAA61251.1.
AF297093 Genomic DNA. Translation: AAG30420.1.
DQ364250 mRNA. Translation: ABC96774.1.
AC006985 Genomic DNA. No translation available.
AC114812 Genomic DNA. No translation available.
BM924331 mRNA. No translation available.
AF014112 Genomic DNA. Translation: AAB87411.1.
CCDSCCDS2507.1. [P19224-1]
CCDS2508.1. [P19224-2]
PIRA31340.
RefSeqNP_001063.2. NM_001072.3. [P19224-1]
UniGeneHs.554822.

3D structure databases

ProteinModelPortalP19224.
SMRP19224. Positions 228-443.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000303174.

Chemistry

BindingDBP19224.
ChEMBLCHEMBL1743316.

Protein family/group databases

CAZyGT1. Glycosyltransferase Family 1.

PTM databases

PhosphoSiteP19224.

Polymorphism databases

DMDM29840832.

Proteomic databases

MaxQBP19224.
PaxDbP19224.
PRIDEP19224.

Protocols and materials databases

DNASU54578.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000305139; ENSP00000303174; ENSG00000167165. [P19224-1]
ENST00000373424; ENSP00000362523; ENSG00000167165. [P19224-2]
GeneID54578.
KEGGhsa:54578.
UCSCuc002vuv.4. human. [P19224-1]

Organism-specific databases

CTD54578.
GeneCardsGC02P234600.
HGNCHGNC:12538. UGT1A6.
HPACAB009819.
MIM191740. gene.
606431. gene.
neXtProtNX_P19224.
PharmGKBPA37181.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1819.
HOGENOMHOG000220832.
HOVERGENHBG004033.
KOK00699.
OMALKESKHY.
OrthoDBEOG78H3T2.
PhylomeDBP19224.
TreeFamTF315472.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKP19224.

Gene expression databases

BgeeP19224.
GenevestigatorP19224.

Family and domain databases

InterProIPR002213. UDP_glucos_trans.
[Graphical view]
PANTHERPTHR11926. PTHR11926. 1 hit.
PfamPF00201. UDPGT. 1 hit.
[Graphical view]
PROSITEPS00375. UDPGT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiUGT1A6.
GenomeRNAi54578.
NextBio35481513.
PROP19224.
SOURCESearch...

Entry information

Entry nameUD16_HUMAN
AccessionPrimary (citable) accession number: P19224
Secondary accession number(s): A6NKK6, B8K289, Q96TE7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: April 11, 2003
Last modified: July 9, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM