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Protein

UDP-glucuronosyltransferase 1-8

Gene

UGT1A8

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

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.

Catalytic activityi

UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside.1 Publication

GO - Molecular functioni

  • drug binding Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • enzyme inhibitor activity Source: BHF-UCL
  • fatty acid binding Source: BHF-UCL
  • glucuronosyltransferase activity Source: BHF-UCL
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • retinoic acid binding Source: BHF-UCL
  • steroid binding Source: BHF-UCL

GO - Biological processi

  • cellular glucuronidation Source: BHF-UCL
  • coumarin metabolic process Source: BHF-UCL
  • drug metabolic process Source: BHF-UCL
  • fatty acid metabolic process Source: BHF-UCL
  • flavone metabolic process Source: BHF-UCL
  • flavonoid glucuronidation Source: BHF-UCL
  • negative regulation of cellular glucuronidation Source: UniProtKB
  • negative regulation of fatty acid metabolic process Source: BHF-UCL
  • negative regulation of glucuronosyltransferase activity Source: BHF-UCL
  • negative regulation of steroid metabolic process Source: BHF-UCL
  • retinoic acid metabolic process Source: BHF-UCL
  • steroid metabolic process Source: BHF-UCL
  • xenobiotic glucuronidation Source: BHF-UCL

Keywordsi

Molecular functionGlycosyltransferase, Transferase

Enzyme and pathway databases

BioCyciMetaCyc:HS10706-MONOMER
BRENDAi2.4.1.17 2681
ReactomeiR-HSA-156588 Glucuronidation
SABIO-RKiQ9HAW9
SIGNORiQ9HAW9

Protein family/group databases

CAZyiGT1 Glycosyltransferase Family 1

Chemistry databases

SwissLipidsiSLP:000001710

Names & Taxonomyi

Protein namesi
Recommended name:
UDP-glucuronosyltransferase 1-8 (EC:2.4.1.17)
Short name:
UDPGT 1-8
Short name:
UGT1*8
Short name:
UGT1-08
Short name:
UGT1.8
Alternative name(s):
UDP-glucuronosyltransferase 1-H
Short name:
UGT-1H
Short name:
UGT1H
UDP-glucuronosyltransferase 1A8
Gene namesi
Name:UGT1A8
Synonyms:GNT1, UGT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000242366.3
HGNCiHGNC:12540 UGT1A8
MIMi191740 gene
606433 gene
neXtProtiNX_Q9HAW9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei488 – 504HelicalSequence analysisAdd BLAST17

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

DisGeNETi54576
OpenTargetsiENSG00000242366
PharmGKBiPA37183

Chemistry databases

ChEMBLiCHEMBL1743318
DrugBankiDB00861 Diflunisal
DB00295 Morphine
DB00688 Mycophenolate mofetil
DB00818 Propofol
DB00197 Troglitazone
DB00313 Valproic Acid

Polymorphism and mutation databases

BioMutaiUGT1A8
DMDMi29839637

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000003600726 – 530UDP-glucuronosyltransferase 1-8Add BLAST505

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi71N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi292N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi344N-linked (GlcNAc...) asparagine1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ9HAW9
PaxDbiQ9HAW9
PeptideAtlasiQ9HAW9
PRIDEiQ9HAW9
ProteomicsDBi81456

PTM databases

iPTMnetiQ9HAW9
PhosphoSitePlusiQ9HAW9

Expressioni

Tissue specificityi

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 (PubMed:18004212).2 Publications

Gene expression databases

BgeeiENSG00000242366
ExpressionAtlasiQ9HAW9 baseline and differential
GenevisibleiQ9HAW9 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, UGT1A9 and UGT1A10.1 Publication

GO - Molecular functioni

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

Protein-protein interaction databases

IntActiQ9HAW9, 7 interactors
STRINGi9606.ENSP00000362549

Chemistry databases

BindingDBiQ9HAW9

Structurei

3D structure databases

ProteinModelPortaliQ9HAW9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the UDP-glycosyltransferase family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1192 Eukaryota
COG1819 LUCA
GeneTreeiENSGT00760000118949
HOGENOMiHOG000220832
HOVERGENiHBG004033
InParanoidiQ9HAW9
KOiK00699
OMAiIPCSLDM
OrthoDBiEOG091G03YY
PhylomeDBiQ9HAW9
TreeFamiTF315472

Family and domain databases

InterProiView protein in InterPro
IPR002213 UDP_glucos_trans
IPR035595 UDP_glycos_trans_CS
PfamiView protein in Pfam
PF00201 UDPGT, 1 hit
PROSITEiView protein in PROSITE
PS00375 UDPGT, 1 hit

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: Q9HAW9-1) [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
MARTGWTSPI PLCVSLLLTC GFAEAGKLLV VPMDGSHWFT MQSVVEKLIL
60 70 80 90 100
RGHEVVVVMP EVSWQLGKSL NCTVKTYSTS YTLEDLDREF MDFADAQWKA
110 120 130 140 150
QVRSLFSLFL SSSNGFFNLF FSHCRSLFND RKLVEYLKES SFDAVFLDPF
160 170 180 190 200
DACGLIVAKY FSLPSVVFAR GIACHYLEEG AQCPAPLSYV PRILLGFSDA
210 220 230 240 250
MTFKERVRNH IMHLEEHLFC QYFSKNALEI 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):59,742
Last modified:March 1, 2001 - v1
Checksum:iAD838436940F4190
GO
Isoform 2 (identifier: Q9HAW9-2) [UniParc]FASTAAdd to basket
Also known as: i2, UGT1A8s

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

Show »
Length:441
Mass (Da):49,518
Checksum:iCE3BAC9FD06D0565
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05246353H → N. Corresponds to variant dbSNP:rs45504099Ensembl.1
Natural variantiVAR_015543132K → R2 Publications1
Natural variantiVAR_058585144A → V1 PublicationCorresponds to variant dbSNP:rs17862841Ensembl.1
Natural variantiVAR_015544154G → A2 Publications1
Natural variantiVAR_015545173A → G in allele UGT1A8*2. 5 PublicationsCorresponds to variant dbSNP:rs1042597Ensembl.1
Natural variantiVAR_061871173A → V. Corresponds to variant dbSNP:rs1042597Ensembl.1
Natural variantiVAR_015546202T → A2 Publications1
Natural variantiVAR_015547212M → L2 PublicationsCorresponds to variant dbSNP:rs1126803Ensembl.1
Natural variantiVAR_058586231A → T1 PublicationCorresponds to variant dbSNP:rs72551325Ensembl.1
Natural variantiVAR_015549277C → Y in allele UGT1A8*3; dramatic reduction in catalytic activity. 2 PublicationsCorresponds to variant dbSNP:rs17863762Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_053964432 – 530SYKEN…KSKTH → RKKQQSGRQM in isoform 2. CuratedAdd BLAST99

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS33402.1 [Q9HAW9-1]
RefSeqiNP_061949.3, NM_019076.4 [Q9HAW9-1]
UniGeneiHs.554822

Genome annotation databases

EnsembliENST00000373450; ENSP00000362549; ENSG00000242366 [Q9HAW9-1]
GeneIDi54576
KEGGihsa:54576
UCSCiuc002vup.4 human [Q9HAW9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiUD18_HUMAN
AccessioniPrimary (citable) accession number: Q9HAW9
Secondary accession number(s): B2R8S3
, B8K290, O14928, Q8TEX4, Q8WTQ9, Q8WX85
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 11, 2003
Last sequence update: March 1, 2001
Last modified: June 20, 2018
This is version 148 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

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