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Protein

UDP-glucuronosyltransferase 1-10

Gene

UGT1A10

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • glucuronosyltransferase activity Source: BHF-UCL
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase C binding Source: BHF-UCL

GO - Biological processi

  • cellular glucuronidation Source: BHF-UCL
  • cellular response to hormone stimulus Source: GO_Central
  • flavone metabolic process Source: BHF-UCL
  • flavonoid biosynthetic process Source: GO_Central
  • flavonoid glucuronidation Source: GO_Central
  • negative regulation of cellular glucuronidation Source: BHF-UCL
  • negative regulation of fatty acid metabolic process Source: BHF-UCL
  • negative regulation of transferase activity Source: BHF-UCL
  • xenobiotic glucuronidation Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Transferase

Enzyme and pathway databases

BRENDAi2.4.1.17. 2681.
SABIO-RKQ9HAW8.

Protein family/group databases

CAZyiGT1. Glycosyltransferase Family 1.

Names & Taxonomyi

Protein namesi
Recommended name:
UDP-glucuronosyltransferase 1-10 (EC:2.4.1.17)
Short name:
UDPGT 1-10
Short name:
UGT1*10
Short name:
UGT1-10
Short name:
UGT1.10
Alternative name(s):
UDP-glucuronosyltransferase 1-J
Short name:
UGT-1J
Short name:
UGT1J
UDP-glucuronosyltransferase 1A10
Gene namesi
Name:UGT1A10
Synonyms:GNT1, UGT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:12531. UGT1A10.

Subcellular locationi

Topology

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

GO - Cellular componenti

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA37174.

Chemistry

DrugBankiDB00316. Acetaminophen.
DB00749. Etodolac.
DB00678. Losartan.
DB00688. Mycophenolate mofetil.
DB00313. Valproic Acid.

Polymorphism and mutation databases

BioMutaiUGT1A10.
DMDMi29839636.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence AnalysisAdd
BLAST
Chaini26 – 530505UDP-glucuronosyltransferase 1-10PRO_0000036009Add
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

PaxDbiQ9HAW8.
PRIDEiQ9HAW8.

PTM databases

PhosphoSiteiQ9HAW8.

Expressioni

Tissue specificityi

Liver and colon. Isoform 1 and isoform 2 are expressed in colon, esophagus and small intestine; isoform 2 but not isoform 1 is expressed in liver or kidney (PubMed:18004212).2 Publications

Gene expression databases

BgeeiQ9HAW8.
ExpressionAtlasiQ9HAW8. baseline.
GenevisibleiQ9HAW8. HS.

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, UGT1A7, UGT1A8 and UGT1A9.1 Publication

Protein-protein interaction databases

BioGridi120053. 17 interactions.
IntActiQ9HAW8. 7 interactions.
STRINGi9606.ENSP00000343838.

Structurei

3D structure databases

ProteinModelPortaliQ9HAW8.
SMRiQ9HAW8. 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.
InParanoidiQ9HAW8.
KOiK00699.
OMAiEVINNTR.
OrthoDBiEOG7353X5.
PhylomeDBiQ9HAW8.
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. AlignAdd to basket

Isoform 1 (identifier: Q9HAW8-1) [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
MARAGWTSPV PLCVCLLLTC GFAEAGKLLV VPMDGSHWFT MQSVVEKLIL
60 70 80 90 100
RGHEVVVVMP EVSWQLERSL NCTVKTYSTS YTLEDQNREF MVFAHAQWKA
110 120 130 140 150
QAQSIFSLLM SSSSGFLDLF FSHCRSLFND RKLVEYLKES SFDAVFLDPF
160 170 180 190 200
DTCGLIVAKY FSLPSVVFTR GIFCHHLEEG AQCPAPLSYV PNDLLGFSDA
210 220 230 240 250
MTFKERVWNH IVHLEDHLFC QYLFRNALEI ASEILQTPVT AYDLYSHTSI
260 270 280 290 300
WLLRTDFVLD YPKPVMPNMI FIGGINCHQG KPLPMEFEAY 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):59,810
Last modified:March 1, 2001 - v1
Checksum:i73774EEEC7FE37BA
GO
Isoform 2 (identifier: Q9HAW8-2) [UniParc]FASTAAdd to basket

Also known as: i2, UGT1A10s

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

Show »
Length:441
Mass (Da):49,586
Checksum:i06D89D99B1C0300E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1 – 2323MARAG…TCGFA → MAPRRVDQPRSFMCVSTADL WLC (PubMed:9271343).CuratedAdd
BLAST
Sequence conflicti40 – 401T → A in AAB81537 (PubMed:9271343).Curated
Sequence conflicti175 – 1751H → R in AAB81537 (PubMed:9271343).Curated
Sequence conflicti224 – 2241F → L in AAB81537 (PubMed:9271343).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti59 – 591M → I.1 Publication
Corresponds to variant rs56935833 [ dbSNP | Ensembl ].
VAR_018354
Natural varianti139 – 1391E → K.
Corresponds to variant rs10187694 [ dbSNP | Ensembl ].
VAR_052464
Natural varianti202 – 2021T → I.1 Publication
Corresponds to variant rs58704432 [ dbSNP | Ensembl ].
VAR_018355
Natural varianti244 – 2441L → I.
Corresponds to variant rs28969685 [ dbSNP | Ensembl ].
VAR_052465

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei432 – 53099SYKEN…KSKTH → RKKQQSGRQM in isoform 2. 1 PublicationVSP_053966Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U89508 mRNA. Translation: AAB81537.1.
AF297093 Genomic DNA. Translation: AAG30417.1.
AC006985 Genomic DNA. No translation available.
AC019072 Genomic DNA. No translation available.
BC020971 mRNA. Translation: AAH20971.1.
BC053576 mRNA. Translation: AAH53576.1.
BC069210 mRNA. Translation: AAH69210.2.
CCDSiCCDS33403.1. [Q9HAW8-1]
PIRiJC5656.
RefSeqiNP_061948.1. NM_019075.2. [Q9HAW8-1]
UniGeneiHs.554822.

Genome annotation databases

EnsembliENST00000344644; ENSP00000343838; ENSG00000242515. [Q9HAW8-1]
ENST00000373445; ENSP00000362544; ENSG00000242515. [Q9HAW8-2]
GeneIDi54575.
KEGGihsa:54575.
UCSCiuc002vuq.3. human.
uc002vur.3. human. [Q9HAW8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U89508 mRNA. Translation: AAB81537.1.
AF297093 Genomic DNA. Translation: AAG30417.1.
AC006985 Genomic DNA. No translation available.
AC019072 Genomic DNA. No translation available.
BC020971 mRNA. Translation: AAH20971.1.
BC053576 mRNA. Translation: AAH53576.1.
BC069210 mRNA. Translation: AAH69210.2.
CCDSiCCDS33403.1. [Q9HAW8-1]
PIRiJC5656.
RefSeqiNP_061948.1. NM_019075.2. [Q9HAW8-1]
UniGeneiHs.554822.

3D structure databases

ProteinModelPortaliQ9HAW8.
SMRiQ9HAW8. Positions 280-441.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120053. 17 interactions.
IntActiQ9HAW8. 7 interactions.
STRINGi9606.ENSP00000343838.

Chemistry

BindingDBiQ9HAW8.
ChEMBLiCHEMBL1743320.
DrugBankiDB00316. Acetaminophen.
DB00749. Etodolac.
DB00678. Losartan.
DB00688. Mycophenolate mofetil.
DB00313. Valproic Acid.

Protein family/group databases

CAZyiGT1. Glycosyltransferase Family 1.

PTM databases

PhosphoSiteiQ9HAW8.

Polymorphism and mutation databases

BioMutaiUGT1A10.
DMDMi29839636.

Proteomic databases

PaxDbiQ9HAW8.
PRIDEiQ9HAW8.

Protocols and materials databases

DNASUi54575.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000344644; ENSP00000343838; ENSG00000242515. [Q9HAW8-1]
ENST00000373445; ENSP00000362544; ENSG00000242515. [Q9HAW8-2]
GeneIDi54575.
KEGGihsa:54575.
UCSCiuc002vuq.3. human.
uc002vur.3. human. [Q9HAW8-1]

Organism-specific databases

CTDi54575.
GeneCardsiGC02P234545.
HGNCiHGNC:12531. UGT1A10.
MIMi191740. gene.
606435. gene.
neXtProtiNX_Q9HAW8.
PharmGKBiPA37174.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1819.
GeneTreeiENSGT00760000118949.
HOGENOMiHOG000220832.
HOVERGENiHBG004033.
InParanoidiQ9HAW8.
KOiK00699.
OMAiEVINNTR.
OrthoDBiEOG7353X5.
PhylomeDBiQ9HAW8.
TreeFamiTF315472.

Enzyme and pathway databases

BRENDAi2.4.1.17. 2681.
SABIO-RKQ9HAW8.

Miscellaneous databases

GeneWikiiUGT1A10.
GenomeRNAii54575.
NextBioi57074.
PROiQ9HAW8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9HAW8.
ExpressionAtlasiQ9HAW8. baseline.
GenevisibleiQ9HAW8. HS.

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]
ProtoNetiSearch...

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] (ISOFORM 1), 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].
  3. "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].
  4. "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] (ISOFORMS 1 AND 2).
    Tissue: Colon and Kidney.
  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: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
  6. "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.
  7. "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: SUBUNIT.
  8. Cited for: VARIANTS ILE-59 AND ILE-202.

Entry informationi

Entry nameiUD110_HUMAN
AccessioniPrimary (citable) accession number: Q9HAW8
Secondary accession number(s): O00474, Q6NT91, Q7Z6H8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 11, 2003
Last sequence update: March 1, 2001
Last modified: June 24, 2015
This is version 132 of the entry and version 1 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.