Reviewed, UniProtKB/Swiss-Prot P19224 (UD16_HUMAN)

Names and origin

Protein names

Recommended name:
    UDP-glucuronosyltransferase 1-6
    EC=2.4.1.17
Alternative name(s):
    UDP-glucuronosyltransferase 1A6
      Short name=UDPGT
      Short name=UGT1*6
    UGT1-06
      Short name=UGT1.6
    UGT-1F
      Short name=UGT1F
    Phenol-metabolizing UDP-glucuronosyltransferase

Gene names

Name:	UGT1A6
Synonyms:	GNT1, UGT1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	532 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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 has specificity for phenols.
Catalytic activity	UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside.
Subcellular location	Microsome. Endoplasmic reticulum membrane; Single-pass membrane protein Potential.
Tissue specificity	Expressed in skin, kidney and liver. Ref.1
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.
Sequence similarities	Belongs to the UDP-glycosyltransferase family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane
Molecular function	Glycosyltransferase Transferase
PTM	Glycoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	xenobiotic metabolic process Ref.2 Inferred from direct assay. Source: UniProtKB
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microsome Non-traceable author statement. Source: UniProtKB
Molecular function	glucuronosyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

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

Note: A number of isoforms may be produced. Isoforms have a different N-terminal domain and a common C-terminal domain of 245 residues.

Isoform 1 (identifier: P19224-1)

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 – 26	26	Potential
	Chain	27 – 532	506	UDP-glucuronosyltransferase 1-6		PRO_0000036005
Regions
	Transmembrane	490 – 506	17	Potential
Amino acid modifications
	Glycosylation	294	1	N-linked (GlcNAc...) Potential
	Glycosylation	346	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	7	1	S → A in allele UGT1A6*2, allele UGT1A6*3 and allele UGT1A6*4. dbSNP rs6759892. Ref.6		VAR_024685
	Natural variant	70	1	S → Y: dbSNP rs1042708. Ref.1		VAR_026628
	Natural variant	181	1	T → A in allele UGT1A6*2. dbSNP rs2070959. Ref.6 Ref.5		VAR_014784
	Natural variant	184	1	R → S in allele UGT1A6*2 and allele UGT1A6*4. dbSNP rs1105879. Ref.6 Ref.5		VAR_015559
	Natural variant	510	1	A → P: dbSNP rs1042709. Ref.1		VAR_026629
Experimental info
	Sequence conflict	231	1	E → K in AAA61251. Ref.1
	Sequence conflict	247 – 249	3	YQK → SE in AAA61251. Ref.1
	Sequence conflict	328	1	I → N in AAA61251. Ref.1
	Sequence conflict	514	1	R → P in AAA61251. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 11, 2003. Version 2. Checksum: 4A9EA6A88CBC3136	FASTA	532	60,751
	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

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: 1339448] [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: 3141926] [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: 11434514] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: 9466822] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33.
[5]	"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: 9429234] [Abstract] Cited for: VARIANTS ALA-181 AND SER-184.
[6]	"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: 15284531] [Abstract] Cited for: VARIANTS ALA-7; ALA-181 AND SER-184.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M84130 Genomic DNA. Translation: AAC41717.1. M84124, M84122, M84123 Genomic DNA. Translation: AAA61247.1. Sequence problems. J04093 mRNA. Translation: AAA61251.1. AF014112 Genomic DNA. Translation: AAB87411.1. AF297093 Genomic DNA. Translation: AAG30420.1.
IPI	IPI00451965.
PIR	A31340.
RefSeq	NP_001063.2.
UniGene	Hs.554822
3D structure databases
ModBase	Search...
Protein family/group databases
CAZy	GT1. Glycosyltransferase Family 1.
PTM databases
PhosphoSite	P19224.
Proteomic databases
PRIDE	P19224.
Genome annotation databases
Ensembl	ENSG00000167165. Homo sapiens. [Contig view]
GeneID	54578.
KEGG	hsa:54578.
UCSC	uc002vuv.2. human.
Organism-specific databases
GeneCards	GC02P234217.
HGNC	HGNC:12538. UGT1A6.
MIM	191740. gene. 606431. gene.
Orphanet	205. Crigler-Najjar syndrome. 357. Gilbert syndrome. 2312. Hyperbilirubinemia transient familial neonatal.
PharmGKB	PA37181.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P19224.
OMA	P19224. WLSMKDI.
Enzyme and pathway databases
Reactome	REACT_13433. Biological oxidations.
Gene expression databases
ArrayExpress	P19224.
Bgee	P19224.
GermOnline	ENSG00000167165. Homo sapiens.
Family and domain databases
InterPro	IPR002213. UDP_glucos_trans. [Graphical view]
PANTHER	PTHR11926. UDP_glucos_trans. 1 hit.
Pfam	PF00201. UDPGT. 1 hit. [Graphical view]
PROSITE	PS00375. UDPGT. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	57086.
SOURCE	Search...

Entry information

Entry name

UD16_HUMAN

Accession

Primary (citable) accession number: P19224
Secondary accession number(s): Q96TE7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	April 11, 2003
Last modified:	July 7, 2009
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)