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P19224

- UD16_HUMAN

UniProt

P19224 - UD16_HUMAN

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Protein
UDP-glucuronosyltransferase 1-6
Gene
UGT1A6, GNT1, UGT1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks transferase activity but acts as a negative regulator of isoform 1 By similarity.

Catalytic activityi

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

GO - Molecular functioni

  1. enzyme binding Source: BHF-UCL
  2. glucuronosyltransferase activity Source: UniProt
  3. protein heterodimerization activity Source: UniProt
  4. protein homodimerization activity Source: UniProt

GO - Biological processi

  1. cellular glucuronidation Source: UniProt
  2. small molecule metabolic process Source: Reactome
  3. xenobiotic metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Enzyme and pathway databases

ReactomeiREACT_6784. Glucuronidation.
SABIO-RKP19224.

Protein family/group databases

CAZyiGT1. Glycosyltransferase Family 1.

Names & Taxonomyi

Protein namesi
Recommended name:
UDP-glucuronosyltransferase 1-6 (EC:2.4.1.17)
Short name:
UDPGT 1-6
Short name:
UGT1*6
Short name:
UGT1-06
Short name:
UGT1.6
Alternative name(s):
Phenol-metabolizing UDP-glucuronosyltransferase
UDP-glucuronosyltransferase 1-F
Short name:
UGT-1F
Short name:
UGT1F
UDP-glucuronosyltransferase 1A6
Gene namesi
Name:UGT1A6
Synonyms:GNT1, UGT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:12538. UGT1A6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei490 – 50617Helical; Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProt
  2. endoplasmic reticulum membrane Source: Reactome
  3. extracellular vesicular exosome Source: UniProt
  4. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37181.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626 Reviewed prediction
Add
BLAST
Chaini27 – 532506UDP-glucuronosyltransferase 1-6
PRO_0000036005Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi294 – 2941N-linked (GlcNAc...) Reviewed prediction
Glycosylationi346 – 3461N-linked (GlcNAc...) Reviewed prediction

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP19224.
PaxDbiP19224.
PRIDEiP19224.

PTM databases

PhosphoSiteiP19224.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiP19224.
GenevestigatoriP19224.

Organism-specific databases

HPAiCAB009819.

Interactioni

Subunit structurei

Isoform 1 interacts with isoform 3/i2 suggesting 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 UGT1A10.1 Publication

Protein-protein interaction databases

IntActiP19224. 7 interactions.
STRINGi9606.ENSP00000303174.

Structurei

3D structure databases

ProteinModelPortaliP19224.
SMRiP19224. Positions 228-443.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1819.
HOGENOMiHOG000220832.
HOVERGENiHBG004033.
KOiK00699.
OMAiLKESKHY.
OrthoDBiEOG78H3T2.
PhylomeDBiP19224.
TreeFamiTF315472.

Family and domain databases

InterProiIPR002213. UDP_glucos_trans.
[Graphical view]
PANTHERiPTHR11926. PTHR11926. 1 hit.
PfamiPF00201. UDPGT. 1 hit.
[Graphical view]
PROSITEiPS00375. UDPGT. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P19224-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MACLLRSFQR ISAGVFFLAL WGMVVGDKLL VVPQDGSHWL SMKDIVEVLS    50
DRGHEIVVVV PEVNLLLKES KYYTRKIYPV PYDQEELKNR YQSFGNNHFA 100
ERSFLTAPQT EYRNNMIVIG LYFINCQSLL QDRDTLNFFK ESKFDALFTD 150
PALPCGVILA EYLGLPSVYL FRGFPCSLEH TFSRSPDPVS YIPRCYTKFS 200
DHMTFSQRVA NFLVNLLEPY LFYCLFSKYE ELASAVLKRD VDIITLYQKV 250
SVWLLRYDFV LEYPRPVMPN MVFIGGINCK KRKDLSQEFE AYINASGEHG 300
IVVFSLGSMV SEIPEKKAMA IADALGKIPQ TVLWRYTGTR PSNLANNTIL 350
VKWLPQNDLL GHPMTRAFIT HAGSHGVYES ICNGVPMVMM PLFGDQMDNA 400
KRMETKGAGV TLNVLEMTSE DLENALKAVI NDKSYKENIM RLSSLHKDRP 450
VEPLDLAVFW VEFVMRHKGA PHLRPAAHDL TWYQYHSLDV IGFLLAVVLT 500
VAFITFKCCA YGYRKCLGKK GRVKKAHKSK TH 532
Length:532
Mass (Da):60,751
Last modified:April 11, 2003 - v2
Checksum:i4A9EA6A88CBC3136
GO
Isoform 2 (identifier: P19224-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-267: Missing.

Note: No experimental confirmation available.

Show »
Length:265
Mass (Da):29,647
Checksum:iC0DEE8F8EC498CFD
GO
Isoform 3 (identifier: P19224-3) [UniParc]FASTAAdd to Basket

Also known as: i2, UGT1A6s

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

Show »
Length:443
Mass (Da):50,528
Checksum:iD49A8F5D16A09EDD
GO

Sequence cautioni

The sequence BM924331 differs from that shown. Reason: Probable cloning artifact.
The sequence BM924331 differs from that shown. Reason: Frameshift at positions 451 and 463.
The sequence BM924331 differs from that shown. Reason: Erroneous termination at position 420. Translated as Glu.

Polymorphismi

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71S → A in allele UGT1A6*2, allele UGT1A6*3 and allele UGT1A6*4. 1 Publication
Corresponds to variant rs6759892 [ dbSNP | Ensembl ].
VAR_024685
Natural varianti70 – 701S → Y.1 Publication
Corresponds to variant rs1042708 [ dbSNP | Ensembl ].
VAR_026628
Natural varianti181 – 1811T → A in allele UGT1A6*2. 4 Publications
Corresponds to variant rs2070959 [ dbSNP | Ensembl ].
VAR_014784
Natural varianti184 – 1841R → S in allele UGT1A6*2 and allele UGT1A6*4. 4 Publications
Corresponds to variant rs1105879 [ dbSNP | Ensembl ].
VAR_015559
Natural varianti510 – 5101A → P.1 Publication
Corresponds to variant rs1042709 [ dbSNP | Ensembl ].
VAR_026629

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 267267Missing in isoform 2.
VSP_045779Add
BLAST
Alternative sequencei434 – 53299SYKEN…KSKTH → RKKQQSGRQM in isoform 3.
VSP_053962Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti231 – 2311E → K in AAA61251. 1 Publication
Sequence conflicti247 – 2493YQK → SE in AAA61251. 1 Publication
Sequence conflicti328 – 3281I → N in AAA61251. 1 Publication
Sequence conflicti419 – 4191S → F in BM924331. 1 Publication
Sequence conflicti446 – 4461H → S in BM924331. 1 Publication
Sequence conflicti468 – 4681K → Q in BM924331. 1 Publication
Sequence conflicti476 – 4772AA → GS in BM924331. 1 Publication
Sequence conflicti514 – 5141R → P in AAA61251. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS2507.1. [P19224-1]
CCDS2508.1. [P19224-2]
PIRiA31340.
RefSeqiNP_001063.2. NM_001072.3. [P19224-1]
UniGeneiHs.554822.

Genome annotation databases

EnsembliENST00000305139; ENSP00000303174; ENSG00000167165. [P19224-1]
ENST00000373424; ENSP00000362523; ENSG00000167165. [P19224-2]
GeneIDi54578.
KEGGihsa:54578.
UCSCiuc002vuv.4. human. [P19224-1]

Polymorphism databases

DMDMi29840832.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS2507.1. [P19224-1 ]
CCDS2508.1. [P19224-2 ]
PIRi A31340.
RefSeqi NP_001063.2. NM_001072.3. [P19224-1 ]
UniGenei Hs.554822.

3D structure databases

ProteinModelPortali P19224.
SMRi P19224. Positions 228-443.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P19224. 7 interactions.
STRINGi 9606.ENSP00000303174.

Chemistry

BindingDBi P19224.
ChEMBLi CHEMBL1743316.

Protein family/group databases

CAZyi GT1. Glycosyltransferase Family 1.

PTM databases

PhosphoSitei P19224.

Polymorphism databases

DMDMi 29840832.

Proteomic databases

MaxQBi P19224.
PaxDbi P19224.
PRIDEi P19224.

Protocols and materials databases

DNASUi 54578.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000305139 ; ENSP00000303174 ; ENSG00000167165 . [P19224-1 ]
ENST00000373424 ; ENSP00000362523 ; ENSG00000167165 . [P19224-2 ]
GeneIDi 54578.
KEGGi hsa:54578.
UCSCi uc002vuv.4. human. [P19224-1 ]

Organism-specific databases

CTDi 54578.
GeneCardsi GC02P234600.
HGNCi HGNC:12538. UGT1A6.
HPAi CAB009819.
MIMi 191740. gene.
606431. gene.
neXtProti NX_P19224.
PharmGKBi PA37181.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1819.
HOGENOMi HOG000220832.
HOVERGENi HBG004033.
KOi K00699.
OMAi LKESKHY.
OrthoDBi EOG78H3T2.
PhylomeDBi P19224.
TreeFami TF315472.

Enzyme and pathway databases

Reactomei REACT_6784. Glucuronidation.
SABIO-RK P19224.

Miscellaneous databases

GeneWikii UGT1A6.
GenomeRNAii 54578.
NextBioi 35481513.
PROi P19224.
SOURCEi Search...

Gene expression databases

Bgeei P19224.
Genevestigatori P19224.

Family and domain databases

InterProi IPR002213. UDP_glucos_trans.
[Graphical view ]
PANTHERi PTHR11926. PTHR11926. 1 hit.
Pfami PF00201. UDPGT. 1 hit.
[Graphical view ]
PROSITEi PS00375. UDPGT. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiUD16_HUMAN
AccessioniPrimary (citable) accession number: P19224
Secondary accession number(s): A6NKK6, B8K289, Q96TE7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: April 11, 2003
Last modified: September 3, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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