P19224 (UD16_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	532 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 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.
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.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Glycosyltransferase Transferase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	small molecule metabolic process Traceable author statement. Source: Reactome xenobiotic metabolic process Inferred from direct assay Ref.2. Source: UniProtKB
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	enzyme binding Inferred from direct assay PubMed 20610558. Source: BHF-UCL glucuronosyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [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.

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.

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	Helical; Potential
Amino acid modifications
	Glycosylation	294	1	N-linked (GlcNAc...) Potential
	Glycosylation	346	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 267	267	Missing in isoform 2.		VSP_045779
	Natural variant	7	1	S → A in allele UGT1A6*2, allele UGT1A6*3 and allele UGT1A6*4. Ref.8 Corresponds to variant rs6759892 [ dbSNP | Ensembl ].		VAR_024685
	Natural variant	70	1	S → Y. Ref.1 Corresponds to variant rs1042708 [ dbSNP | Ensembl ].		VAR_026628
	Natural variant	181	1	T → A in allele UGT1A6*2. Ref.7 Ref.8 Ref.9 Corresponds to variant rs2070959 [ dbSNP | Ensembl ].		VAR_014784
	Natural variant	184	1	R → S in allele UGT1A6*2 and allele UGT1A6*4. Ref.7 Ref.8 Ref.9 Corresponds to variant rs1105879 [ dbSNP | Ensembl ].		VAR_015559
	Natural variant	510	1	A → P. Ref.1 Corresponds to variant rs1042709 [ dbSNP | Ensembl ].		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	419	1	S → F in BM924331. Ref.5
	Sequence conflict	446	1	H → S in BM924331. Ref.5
	Sequence conflict	468	1	K → Q in BM924331. Ref.5
	Sequence conflict	476 – 477	2	AA → GS in BM924331. Ref.5
	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
	Isoform 2 [UniParc]. Checksum: C0DEE8F8EC498CFD	FASTA	265	29,647
	10 20 30 40 50 60 MPNMVFIGGI NCKKRKDLSQ EFEAYINASG EHGIVVFSLG SMVSEIPEKK AMAIADALGK 70 80 90 100 110 120 IPQTVLWRYT GTRPSNLANN TILVKWLPQN DLLGHPMTRA FITHAGSHGV YESICNGVPM 130 140 150 160 170 180 VMMPLFGDQM DNAKRMETKG AGVTLNVLEM TSEDLENALK AVINDKSYKE NIMRLSSLHK 190 200 210 220 230 240 DRPVEPLDLA VFWVEFVMRH KGAPHLRPAA HDLTWYQYHS LDVIGFLLAV VLTVAFITFK 250 260 CCAYGYRKCL GKKGRVKKAH KSKTH

References

	« Hide 'large scale' referencesShow '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]	"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]	"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).
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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. AC006985 Genomic DNA. No translation available. AC114812 Genomic DNA. No translation available. BM924331 mRNA. No translation available. AF014112 Genomic DNA. Translation: AAB87411.1.
IPI	IPI00410366. IPI00451965.
PIR	A31340.
RefSeq	NP_001063.2. NM_001072.3.
UniGene	Hs.554822.
3D structure databases
ProteinModelPortal	P19224.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000303174.
Protein family/group databases
CAZy	GT1. Glycosyltransferase Family 1.
PTM databases
PhosphoSite	P19224.
Polymorphism databases
DMDM	29840832.
Proteomic databases
PaxDb	P19224.
PRIDE	P19224.
Protocols and materials databases
DNASU	54578.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000305139; ENSP00000303174; ENSG00000167165. ENST00000373424; ENSP00000362523; ENSG00000167165.
GeneID	54578.
KEGG	hsa:54578.
UCSC	uc002vuv.4. human.
Organism-specific databases
CTD	54578.
GeneCards	GC02P234600.
HGNC	HGNC:12538. UGT1A6.
HPA	CAB009819.
MIM	191740. gene. 606431. gene.
neXtProt	NX_P19224.
PharmGKB	PA37181.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1819.
HOGENOM	HOG000220832.
HOVERGEN	HBG004033.
KO	K00699.
OMA	LKESKHY.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
SABIO-RK	P19224.
Gene expression databases
ArrayExpress	P19224.
Bgee	P19224.
Genevestigator	P19224.
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	P19224.
ChEMBL	CHEMBL1743316.
GenomeRNAi	54578.
NextBio	57086.
SOURCE	Search...

Entry information

Entry name

UD16_HUMAN

Accession

Primary (citable) accession number: P19224
Secondary accession number(s): A6NKK6, Q96TE7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	April 11, 2003
Last modified:	May 1, 2013
This is version 126 of the entry and version 2 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.