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Q9HAW9 (UD18_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 113. 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 1-8

Short name=UDPGT 1-8
Short name=UGT1*8
Short name=UGT1-08
Short name=UGT1.8
EC=2.4.1.17
Alternative name(s):
UDP-glucuronosyltransferase 1-H
Short name=UGT-1H
Short name=UGT1H
UDP-glucuronosyltransferase 1A8
Gene names
Name:UGT1A8
Synonyms:GNT1, UGT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length530 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. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1. Ref.9 Ref.10 Ref.11

Catalytic activity

UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside. Ref.11

Subunit structure

Isoform 1 interacts with isoform 2/i2suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A9 and UGT1A10. Ref.11

Subcellular location

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

Tissue specificity

Colon specific. Isoform 1 and 2 are expressed in liver, kidney, colon and small intestine; isoform 2 but not isoform 1 is expressed in liver (Ref.9). Ref.1 Ref.9

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.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionGlycosyltransferase
Transferase
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcoumarin metabolic process

Inferred by curator PubMed 19996319. Source: BHF-UCL

drug metabolic process

Inferred from direct assay Ref.11. Source: BHF-UCL

fatty acid metabolic process

Inferred from direct assay Ref.11. Source: BHF-UCL

flavone metabolic process

Inferred from direct assay PubMed 18052087. Source: BHF-UCL

flavonoid glucuronidation

Inferred from direct assay PubMed 20056724. Source: BHF-UCL

negative regulation of catalytic activity

Inferred from direct assay PubMed 19996319Ref.11. Source: GOC

negative regulation of cellular metabolic process

Inferred from direct assay Ref.11. Source: BHF-UCL

negative regulation of fatty acid metabolic process

Inferred by curator PubMed 19996319. Source: BHF-UCL

negative regulation of steroid metabolic process

Inferred by curator PubMed 19996319. Source: BHF-UCL

retinoic acid metabolic process

Inferred by curator PubMed 20308471. Source: BHF-UCL

steroid metabolic process

Inferred by curator PubMed 19996319. Source: BHF-UCL

xenobiotic glucuronidation

Inferred from direct assay PubMed 20056724. Source: BHF-UCL

   Cellular_componentendoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular membrane-bounded organelle

Inferred from direct assay Ref.11. Source: BHF-UCL

   Molecular_functiondrug binding

Inferred by curator Ref.11. Source: BHF-UCL

enzyme binding

Inferred by curator Ref.11. Source: BHF-UCL

enzyme inhibitor activity

Inferred from direct assay PubMed 19996319Ref.11. Source: BHF-UCL

fatty acid binding

Inferred from direct assay PubMed 19996319. Source: BHF-UCL

glucuronosyltransferase activity

Inferred from direct assay PubMed 18052087PubMed 19996319PubMed 20056724PubMed 20308471Ref.11. Source: BHF-UCL

protein heterodimerization activity

Inferred from physical interaction Ref.11. Source: BHF-UCL

protein homodimerization activity

Inferred from physical interaction Ref.11. Source: BHF-UCL

retinoic acid binding

Inferred by curator PubMed 20308471. Source: BHF-UCL

steroid binding

Inferred from direct assay PubMed 19996319. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HAW9-1)

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: Q9HAW9-2)

Also known as: i2; UGT1A8s;

The sequence of this isoform differs from the canonical sequence as follows:
     432-530: SYKENIMRLS...VKKAHKSKTH → RKKQQSGRQM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 530505UDP-glucuronosyltransferase 1-8
PRO_0000036007

Regions

Transmembrane488 – 50417Helical; Potential

Amino acid modifications

Glycosylation711N-linked (GlcNAc...) Potential
Glycosylation2921N-linked (GlcNAc...) Ref.8
Glycosylation3441N-linked (GlcNAc...) Ref.8

Natural variations

Alternative sequence432 – 53099SYKEN…KSKTH → RKKQQSGRQM in isoform 2.
VSP_053964
Natural variant531H → N.
Corresponds to variant rs45504099 [ dbSNP | Ensembl ].
VAR_052463
Natural variant1321K → R. Ref.1 Ref.6
VAR_015543
Natural variant1441A → V. Ref.12
Corresponds to variant rs17862841 [ dbSNP | Ensembl ].
VAR_058585
Natural variant1541G → A. Ref.1 Ref.6
VAR_015544
Natural variant1731A → G in allele UGT1A8*2. Ref.1 Ref.3 Ref.4 Ref.6 Ref.12
Corresponds to variant rs1042597 [ dbSNP | Ensembl ].
VAR_015545
Natural variant1731A → V.
Corresponds to variant rs1042597 [ dbSNP | Ensembl ].
VAR_061871
Natural variant2021T → A. Ref.1 Ref.6
VAR_015546
Natural variant2121M → L. Ref.1 Ref.6
VAR_015547
Natural variant2311A → T. Ref.12
VAR_058586
Natural variant2771C → Y in allele UGT1A8*3; dramatic reduction in catalytic activity. Ref.3 Ref.12
Corresponds to variant rs17863762 [ dbSNP | Ensembl ].
VAR_015549

Sequences

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

Last modified March 1, 2001. Version 1.
Checksum: AD838436940F4190

FASTA53059,742
        10         20         30         40         50         60 
MARTGWTSPI PLCVSLLLTC GFAEAGKLLV VPMDGSHWFT MQSVVEKLIL RGHEVVVVMP 

        70         80         90        100        110        120 
EVSWQLGKSL NCTVKTYSTS YTLEDLDREF MDFADAQWKA QVRSLFSLFL SSSNGFFNLF 

       130        140        150        160        170        180 
FSHCRSLFND RKLVEYLKES SFDAVFLDPF DACGLIVAKY FSLPSVVFAR GIACHYLEEG 

       190        200        210        220        230        240 
AQCPAPLSYV PRILLGFSDA MTFKERVRNH IMHLEEHLFC QYFSKNALEI ASEILQTPVT 

       250        260        270        280        290        300 
AYDLYSHTSI WLLRTDFVLD YPKPVMPNMI FIGGINCHQG KPLPMEFEAY INASGEHGIV 

       310        320        330        340        350        360 
VFSLGSMVSE IPEKKAMAIA DALGKIPQTV LWRYTGTRPS NLANNTILVK WLPQNDLLGH 

       370        380        390        400        410        420 
PMTRAFITHA GSHGVYESIC NGVPMVMMPL FGDQMDNAKR METKGAGVTL NVLEMTSEDL 

       430        440        450        460        470        480 
ENALKAVIND KSYKENIMRL SSLHKDRPVE PLDLAVFWVE FVMRHKGAPH LRPAAHDLTW 

       490        500        510        520        530 
YQYHSLDVIG FLLAVVLTVA FITFKCCAYG YRKCLGKKGR VKKAHKSKTH 

« Hide

Isoform 2 (i2) (UGT1A8s) [UniParc].

Checksum: CE3BAC9FD06D0565
Show »

FASTA44149,518

References

« Hide 'large scale' references
[1]"Expression of the UDP-glucuronosyltransferase 1A locus in human colon. Identification and characterization of the novel extrahepatic UGT1A8."
Strassburg C.P., Manns M.P., Tukey R.H.
J. Biol. Chem. 273:8719-8726(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS ARG-132; ALA-154; GLY-173; ALA-202 AND LEU-212.
[2]"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].
[3]"Identification and functional characterization of UDP-glucuronosyltransferases UGT1A8*1, UGT1A8*2 and UGT1A8*3."
Huang Y.-H., Galijatovic A., Nguyen N., Geske D., Beaton D., Green J., Green M., Peters W.H., Tukey R.H.
Pharmacogenetics 12:287-297(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GLY-173 AND TYR-277.
Tissue: Colon.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLY-173.
Tissue: Tongue.
[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]"Identification of genetic polymorphisms within the human extrahepatic UGT1A8 gene."
Strassburg C.P., Vogel A., Manns M.P.
Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-285, VARIANTS ARG-132; ALA-154; GLY-173; ALA-202 AND LEU-212.
[7]Guillemette C., Levesque E., Girard H., Bernard O.
Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[8]"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-292 AND ASN-344.
Tissue: Liver.
[9]"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: FUNCTION (ISOFORM 2), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[10]"Structure and concentration changes affect characterization of UGT isoform-specific metabolism of isoflavones."
Tang L., Singh R., Liu Z., Hu M.
Mol. Pharm. 6:1466-1482(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"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: CATALYTIC ACTIVITY, FUNCTION (ISOFORM 2), SUBUNIT.
[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 VAL-144; GLY-173; THR-231 AND TYR-277.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF030310 mRNA. Translation: AAB84259.1.
AF297093 Genomic DNA. Translation: AAG30416.1.
AF462267 mRNA. Translation: AAL75963.1.
AF462268 mRNA. Translation: AAL75964.1.
AC006985 Genomic DNA. No translation available.
AC019072 Genomic DNA. No translation available.
AK313488 mRNA. Translation: BAG36270.1.
AF465198 Genomic DNA. Translation: AAL73506.1.
AF465199 Genomic DNA. Translation: AAL73507.1.
AF465200 Genomic DNA. Translation: AAL73508.1.
DQ364251 mRNA. Translation: ABC96775.1.
RefSeqNP_061949.3. NM_019076.4.
UniGeneHs.554822.

3D structure databases

ProteinModelPortalQ9HAW9.
SMRQ9HAW9. Positions 35-62, 280-441.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000362549.

Chemistry

ChEMBLCHEMBL1743318.

Protein family/group databases

CAZyGT1. Glycosyltransferase Family 1.

PTM databases

PhosphoSiteQ9HAW9.

Polymorphism databases

DMDM29839637.

Proteomic databases

PRIDEQ9HAW9.

Protocols and materials databases

DNASU54576.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373450; ENSP00000362549; ENSG00000242366.
GeneID54576.
KEGGhsa:54576.
UCSCuc002vup.3. human. [Q9HAW9-1]

Organism-specific databases

CTD54576.
GeneCardsGC02P234526.
HGNCHGNC:12540. UGT1A8.
MIM191740. gene.
606433. gene.
neXtProtNX_Q9HAW9.
PharmGKBPA37183.
GenAtlasSearch...

Phylogenomic databases

HOGENOMHOG000220832.
HOVERGENHBG004033.
KOK00699.
OMAFITEYEP.
OrthoDBEOG7GBFWS.
PhylomeDBQ9HAW9.
TreeFamTF315472.

Enzyme and pathway databases

BioCycMetaCyc:HS10706-MONOMER.
BRENDA2.4.1.17. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ9HAW9.

Gene expression databases

BgeeQ9HAW9.
GenevestigatorQ9HAW9.

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

GeneWikiUGT1A8.
GenomeRNAi54576.
NextBio57078.
PROQ9HAW9.
SOURCESearch...

Entry information

Entry nameUD18_HUMAN
AccessionPrimary (citable) accession number: Q9HAW9
Secondary accession number(s): B2R8S3 expand/collapse secondary AC list , B8K290, O14928, Q8TEX4, Q8WTQ9, Q8WX85
Entry history
Integrated into UniProtKB/Swiss-Prot: April 11, 2003
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 113 of the entry and version 1 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