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Q9HAW7

- UD17_HUMAN

UniProt

Q9HAW7 - UD17_HUMAN

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Protein

UDP-glucuronosyltransferase 1-7

Gene

UGT1A7

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. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.1 Publication

Catalytic activityi

UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside.2 Publications

GO - Molecular functioni

  1. drug binding Source: BHF-UCL
  2. enzyme binding Source: BHF-UCL
  3. enzyme inhibitor activity Source: BHF-UCL
  4. glucuronosyltransferase activity Source: BHF-UCL
  5. protein heterodimerization activity Source: UniProt
  6. protein homodimerization activity Source: UniProt
  7. protein kinase C binding Source: BHF-UCL
  8. retinoic acid binding Source: BHF-UCL

GO - Biological processi

  1. cellular glucuronidation Source: UniProt
  2. coumarin metabolic process Source: BHF-UCL
  3. drug metabolic process Source: BHF-UCL
  4. excretion Source: BHF-UCL
  5. flavone metabolic process Source: BHF-UCL
  6. flavonoid glucuronidation Source: BHF-UCL
  7. negative regulation of catalytic activity Source: GOC
  8. negative regulation of cellular glucuronidation Source: UniProtKB
  9. negative regulation of fatty acid metabolic process Source: BHF-UCL
  10. retinoic acid metabolic process Source: BHF-UCL
  11. xenobiotic glucuronidation Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Enzyme and pathway databases

BRENDAi2.4.1.17. 2681.
ReactomeiREACT_6784. Glucuronidation.
SABIO-RKQ9HAW7.

Protein family/group databases

CAZyiGT1. Glycosyltransferase Family 1.

Names & Taxonomyi

Protein namesi
Recommended name:
UDP-glucuronosyltransferase 1-7 (EC:2.4.1.17)
Short name:
UDPGT 1-7
Short name:
UGT1*7
Short name:
UGT1-07
Short name:
UGT1.7
Alternative name(s):
UDP-glucuronosyltransferase 1-G
Short name:
UGT-1G
Short name:
UGT1G
UDP-glucuronosyltransferase 1A7
Gene namesi
Name:UGT1A7
Synonyms:GNT1, UGT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:12539. UGT1A7.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei488 – 50417HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum Source: BHF-UCL
  2. endoplasmic reticulum membrane Source: BHF-UCL
  3. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37182.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence AnalysisAdd
BLAST
Chaini26 – 530505UDP-glucuronosyltransferase 1-7PRO_0000036006Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi71 – 711N-linked (GlcNAc...)Sequence Analysis
Glycosylationi292 – 2921N-linked (GlcNAc...)Sequence Analysis
Glycosylationi344 – 3441N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ9HAW7.
PaxDbiQ9HAW7.
PRIDEiQ9HAW7.

PTM databases

PhosphoSiteiQ9HAW7.

Expressioni

Tissue specificityi

Liver and gastric tissue. Isoform 1 and isoform 2 are expressed in esophagus. Neither isoform is expressed in liver, kidney, colon and small intestine (PubMed:18004212).2 Publications

Gene expression databases

BgeeiQ9HAW7.
ExpressionAtlasiQ9HAW7. baseline.
GenevestigatoriQ9HAW7.

Interactioni

Subunit structurei

Isoform 1 interacts with isoform 2/i2 suggesting 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 UGT1A10.2 Publications

Protein-protein interaction databases

BioGridi120055. 1 interaction.
IntActiQ9HAW7. 8 interactions.
STRINGi9606.ENSP00000362525.

Structurei

3D structure databases

ProteinModelPortaliQ9HAW7.
SMRiQ9HAW7. Positions 280-441.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the UDP-glycosyltransferase family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1819.
GeneTreeiENSGT00760000118949.
HOGENOMiHOG000220832.
HOVERGENiHBG004033.
InParanoidiQ9HAW7.
KOiK00699.
OMAiSIAVHRY.
OrthoDBiEOG7GBFWS.
PhylomeDBiQ9HAW7.
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 (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9HAW7-1) [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

        10         20         30         40         50
MARAGWTGLL PLYVCLLLTC GFAKAGKLLV VPMDGSHWFT MQSVVEKLIL
60 70 80 90 100
RGHEVVVVMP EVSWQLGRSL NCTVKTYSTS YTLEDQDREF MVFADARWTA
110 120 130 140 150
PLRSAFSLLT SSSNGIFDLF FSNCRSLFND RKLVEYLKES CFDAVFLDPF
160 170 180 190 200
DACGLIVAKY FSLPSVVFAR GIFCHYLEEG AQCPAPLSYV PRLLLGFSDA
210 220 230 240 250
MTFKERVWNH IMHLEEHLFC PYFFKNVLEI ASEILQTPVT AYDLYSHTSI
260 270 280 290 300
WLLRTDFVLE YPKPVMPNMI FIGGINCHQG KPVPMEFEAY INASGEHGIV
310 320 330 340 350
VFSLGSMVSE IPEKKAMAIA DALGKIPQTV LWRYTGTRPS NLANNTILVK
360 370 380 390 400
WLPQNDLLGH PMTRAFITHA GSHGVYESIC NGVPMVMMPL FGDQMDNAKR
410 420 430 440 450
METKGAGVTL NVLEMTSEDL ENALKAVIND KSYKENIMRL SSLHKDRPVE
460 470 480 490 500
PLDLAVFWVE FVMRHKGAPH LRPAAHDLTW YQYHSLDVIG FLLAVVLTVA
510 520 530
FITFKCCAYG YRKCLGKKGR VKKAHKSKTH
Length:530
Mass (Da):59,819
Last modified:April 23, 2003 - v2
Checksum:i7D759A382AE871D3
GO
Isoform 2 (identifier: Q9HAW7-2) [UniParc]FASTAAdd to Basket

Also known as: i2, UGT1A7s

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

Show »
Length:441
Mass (Da):49,596
Checksum:i95FB1E90EB501A8F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti412 – 4121V → A in AAB81536. (PubMed:9271343)Curated
Sequence conflicti433 – 4331Y → F in AAB81536. (PubMed:9271343)Curated

Polymorphismi

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti129 – 1291N → K in allele UGT1A7*2 and allele UGT1A7*3. 4 Publications
Corresponds to variant rs17868323 [ dbSNP | Ensembl ].
VAR_015556
Natural varianti131 – 1311R → K in allele UGT1A7*2 and allele UGT1A7*3. 4 Publications
VAR_015557
Natural varianti131 – 1311R → Q.
Corresponds to variant rs17868324 [ dbSNP | Ensembl ].
VAR_052462
Natural varianti208 – 2081W → R in allele UGT1A7*3 and allele UGT1A7*4. 3 Publications
Corresponds to variant rs11692021 [ dbSNP | Ensembl ].
VAR_015558

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei432 – 53099SYKEN…KSKTH → RKKQQSGRQM in isoform 2. 1 PublicationVSP_053963Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS2506.1. [Q9HAW7-1]
RefSeqiNP_061950.2. NM_019077.2. [Q9HAW7-1]
UniGeneiHs.554822.

Genome annotation databases

EnsembliENST00000373426; ENSP00000362525; ENSG00000244122. [Q9HAW7-1]
GeneIDi54577.
KEGGihsa:54577.
UCSCiuc002vut.3. human. [Q9HAW7-1]

Polymorphism databases

DMDMi30173486.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSi CCDS2506.1. [Q9HAW7-1 ]
RefSeqi NP_061950.2. NM_019077.2. [Q9HAW7-1 ]
UniGenei Hs.554822.

3D structure databases

ProteinModelPortali Q9HAW7.
SMRi Q9HAW7. Positions 280-441.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 120055. 1 interaction.
IntActi Q9HAW7. 8 interactions.
STRINGi 9606.ENSP00000362525.

Chemistry

BindingDBi Q9HAW7.
ChEMBLi CHEMBL1743317.
DrugBanki DB00688. Mycophenolate mofetil.
DB01024. Mycophenolic acid.

Protein family/group databases

CAZyi GT1. Glycosyltransferase Family 1.

PTM databases

PhosphoSitei Q9HAW7.

Polymorphism databases

DMDMi 30173486.

Proteomic databases

MaxQBi Q9HAW7.
PaxDbi Q9HAW7.
PRIDEi Q9HAW7.

Protocols and materials databases

DNASUi 54577.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000373426 ; ENSP00000362525 ; ENSG00000244122 . [Q9HAW7-1 ]
GeneIDi 54577.
KEGGi hsa:54577.
UCSCi uc002vut.3. human. [Q9HAW7-1 ]

Organism-specific databases

CTDi 54577.
GeneCardsi GC02P234581.
HGNCi HGNC:12539. UGT1A7.
MIMi 191740. gene.
606432. gene.
neXtProti NX_Q9HAW7.
PharmGKBi PA37182.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1819.
GeneTreei ENSGT00760000118949.
HOGENOMi HOG000220832.
HOVERGENi HBG004033.
InParanoidi Q9HAW7.
KOi K00699.
OMAi SIAVHRY.
OrthoDBi EOG7GBFWS.
PhylomeDBi Q9HAW7.
TreeFami TF315472.

Enzyme and pathway databases

BRENDAi 2.4.1.17. 2681.
Reactomei REACT_6784. Glucuronidation.
SABIO-RK Q9HAW7.

Miscellaneous databases

GeneWikii UGT1A7_(gene).
GenomeRNAii 54577.
NextBioi 35481515.
PROi Q9HAW7.
SOURCEi Search...

Gene expression databases

Bgeei Q9HAW7.
ExpressionAtlasi Q9HAW7. baseline.
Genevestigatori Q9HAW7.

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. "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.
    , 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.

Entry informationi

Entry nameiUD17_HUMAN
AccessioniPrimary (citable) accession number: Q9HAW7
Secondary accession number(s): B8K293, O00473
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 11, 2003
Last sequence update: April 23, 2003
Last modified: October 29, 2014
This is version 120 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