Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9HAW7 (UD17_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. 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 1-7

Short name=UDPGT 1-7
Short name=UGT1*7
Short name=UGT1-07
Short name=UGT1.7
EC=2.4.1.17
Alternative name(s):
UDP-glucuronosyltransferase 1-G
Short name=UGT-1G
Short name=UGT1G
UDP-glucuronosyltransferase 1A7
Gene names
Name:UGT1A7
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.5 Ref.6 Ref.7

Catalytic activity

UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside. Ref.5 Ref.6

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, UGT1A8, UGT1A9 and UGT1A10. Ref.6 Ref.7

Subcellular location

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

Tissue specificity

Liver and gastric tissue. Isoform 1 and isoform 2 are expressed in esophagus. Neither isoform isexpressed in liver, kidney, colon and small intestine (Ref.5). Ref.1 Ref.5

Polymorphism

There are four common allelic UGT1A7 variants which exhibit significant differences in catalytic activity towards 3-, 7-, and 9-hydroxy-benzo(a)pyrene. UGT1A7*3 exhibits a 5.8-fold lower relative Vmax compared to UGT1A7*1, whereas UGT1A7*2 and UGT1A7*4 have a 2.6- and 2.8-fold lower relative Vmax than UGT1A7*1, respectively, suggesting that these mutations confer slow glucuronidation phenotype.

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.6. Source: BHF-UCL

excretion

Inferred by curator PubMed 20056724. Source: BHF-UCL

flavone metabolic process

Inferred by curator 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.6. Source: GOC

negative regulation of cellular glucuronidation

Inferred from direct assay Ref.6. Source: UniProtKB

negative regulation of fatty acid metabolic process

Inferred from direct assay Ref.6. Source: BHF-UCL

retinoic acid metabolic process

Inferred by curator PubMed 20308471. Source: BHF-UCL

xenobiotic glucuronidation

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

   Cellular_componentendoplasmic reticulum

Inferred from direct assay PubMed 18556656. Source: BHF-UCL

endoplasmic reticulum membrane

Non-traceable author statement Ref.6. Source: BHF-UCL

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functiondrug binding

Inferred from direct assay Ref.6. Source: BHF-UCL

enzyme binding

Inferred from direct assay Ref.6. Source: BHF-UCL

enzyme inhibitor activity

Inferred from direct assay PubMed 19996319Ref.6. Source: BHF-UCL

glucuronosyltransferase activity

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

protein heterodimerization activity

Inferred from physical interaction. Source: BHF-UCL

protein homodimerization activity

Inferred from physical interaction. Source: BHF-UCL

protein kinase C binding

Inferred from physical interaction. Source: BHF-UCL

retinoic acid binding

Inferred from direct assay PubMed 20308471. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9HAW7-1)

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: Q9HAW7-2)

Also known as: i2; UGT1A7s;

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 1-7
PRO_0000036006

Regions

Transmembrane488 – 50417Helical; Potential

Amino acid modifications

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

Natural variations

Alternative sequence432 – 53099SYKEN…KSKTH → RKKQQSGRQM in isoform 2.
VSP_053963
Natural variant1291N → K in allele UGT1A7*2 and allele UGT1A7*3. Ref.2 Ref.3 Ref.8 Ref.9
Corresponds to variant rs17868323 [ dbSNP | Ensembl ].
VAR_015556
Natural variant1311R → K in allele UGT1A7*2 and allele UGT1A7*3. Ref.2 Ref.3 Ref.8 Ref.9
VAR_015557
Natural variant1311R → Q.
Corresponds to variant rs17868324 [ dbSNP | Ensembl ].
VAR_052462
Natural variant2081W → R in allele UGT1A7*3 and allele UGT1A7*4. Ref.2 Ref.8 Ref.9
Corresponds to variant rs11692021 [ dbSNP | Ensembl ].
VAR_015558

Experimental info

Sequence conflict4121V → A in AAB81536. Ref.1
Sequence conflict4331Y → F in AAB81536. Ref.1

Sequences

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

Last modified April 23, 2003. Version 2.
Checksum: 7D759A382AE871D3

FASTA53059,819
        10         20         30         40         50         60 
MARAGWTGLL PLYVCLLLTC GFAKAGKLLV VPMDGSHWFT MQSVVEKLIL RGHEVVVVMP 

        70         80         90        100        110        120 
EVSWQLGRSL NCTVKTYSTS YTLEDQDREF MVFADARWTA PLRSAFSLLT SSSNGIFDLF 

       130        140        150        160        170        180 
FSNCRSLFND RKLVEYLKES CFDAVFLDPF DACGLIVAKY FSLPSVVFAR GIFCHYLEEG 

       190        200        210        220        230        240 
AQCPAPLSYV PRLLLGFSDA MTFKERVWNH IMHLEEHLFC PYFFKNVLEI ASEILQTPVT 

       250        260        270        280        290        300 
AYDLYSHTSI WLLRTDFVLE YPKPVMPNMI FIGGINCHQG KPVPMEFEAY 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) (UGT1A7s) [UniParc].

Checksum: 95FB1E90EB501A8F
Show »

FASTA44149,596

References

« Hide 'large scale' references
[1]"Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissue."
Strassburg C.P., Oldhafer K., Manns M.P., Tukey R.H.
Mol. Pharmacol. 52:212-220(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[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], VARIANTS LYS-129; LYS-131 AND ARG-208.
[3]Guillemette C., Levesque E., Girard H., Bernard O.
Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS LYS-129 AND LYS-131.
[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. 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].
[5]"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: CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, FUNCTION (ISOFORM 2), TISSUE SPECIFICITY.
[6]"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.
[7]"The relative protein abundance of UGT1A alternative splice variants as a key determinant of glucuronidation activity in vitro."
Rouleau M., Roberge J., Falardeau S.A., Villeneuve L., Guillemette C.
Drug Metab. Dispos. 41:694-697(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT.
[8]"Structural heterogeneity at the UDP-glucuronosyltransferase 1 locus: functional consequences of three novel missense mutations in the human UGT1A7 gene."
Guillemette C., Ritter J.K., Auyeung D.J., Kessler F.K., Housman D.E.
Pharmacogenetics 10:629-644(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LYS-129; LYS-131 AND ARG-208, CHARACTERIZATION OF ALLELES.
[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 LYS-129; LYS-131 AND ARG-208.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U89507 mRNA. Translation: AAB81536.1.
AF297093 Genomic DNA. Translation: AAG30419.1.
DQ383513 mRNA. Translation: ABD42926.1.
AC006985 Genomic DNA. No translation available.
AC114812 Genomic DNA. No translation available.
CCDSCCDS2506.1. [Q9HAW7-1]
RefSeqNP_061950.2. NM_019077.2. [Q9HAW7-1]
UniGeneHs.554822.

3D structure databases

ProteinModelPortalQ9HAW7.
SMRQ9HAW7. Positions 280-441.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000362525.

Chemistry

BindingDBQ9HAW7.
ChEMBLCHEMBL1743317.

Protein family/group databases

CAZyGT1. Glycosyltransferase Family 1.

PTM databases

PhosphoSiteQ9HAW7.

Polymorphism databases

DMDM30173486.

Proteomic databases

MaxQBQ9HAW7.
PaxDbQ9HAW7.
PRIDEQ9HAW7.

Protocols and materials databases

DNASU54577.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373426; ENSP00000362525; ENSG00000244122. [Q9HAW7-1]
GeneID54577.
KEGGhsa:54577.
UCSCuc002vut.3. human. [Q9HAW7-1]

Organism-specific databases

CTD54577.
GeneCardsGC02P234581.
HGNCHGNC:12539. UGT1A7.
MIM191740. gene.
606432. gene.
neXtProtNX_Q9HAW7.
PharmGKBPA37182.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1819.
HOGENOMHOG000220832.
HOVERGENHBG004033.
KOK00699.
OMASIAVHRY.
OrthoDBEOG7GBFWS.
PhylomeDBQ9HAW7.
TreeFamTF315472.

Enzyme and pathway databases

BRENDA2.4.1.17. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ9HAW7.

Gene expression databases

BgeeQ9HAW7.
GenevestigatorQ9HAW7.

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

GeneWikiUGT1A7_(gene).
GenomeRNAi54577.
NextBio35481515.
PROQ9HAW7.
SOURCESearch...

Entry information

Entry nameUD17_HUMAN
AccessionPrimary (citable) accession number: Q9HAW7
Secondary accession number(s): B8K293, O00473
Entry history
Integrated into UniProtKB/Swiss-Prot: April 11, 2003
Last sequence update: April 23, 2003
Last modified: July 9, 2014
This is version 117 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