UD15_HUMAN
ID UD15_HUMAN Reviewed; 534 AA.
AC P35504; B8K294;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=UDP-glucuronosyltransferase 1A5 {ECO:0000303|PubMed:18004212};
DE Short=UGT1A5;
DE EC=2.4.1.17 {ECO:0000269|PubMed:18674515};
DE AltName: Full=UDP-glucuronosyltransferase 1-5;
DE Short=UDPGT 1-5;
DE Short=UGT1*5;
DE Short=UGT1-05;
DE Short=UGT1.5;
DE AltName: Full=UDP-glucuronosyltransferase 1-E;
DE Short=UGT-1E;
DE Short=UGT1E;
DE Flags: Precursor;
GN Name=UGT1A5 {ECO:0000312|HGNC:HGNC:12537}; Synonyms=GNT1, UGT1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1339448; DOI=10.1016/s0021-9258(19)50724-4;
RA Ritter J.K., Chen F., Sheen Y.Y., Tran H.M., Kimura S., Yeatman M.T.,
RA Owens I.S.;
RT "A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-
RT glucuronosyltransferase isozymes with identical carboxyl termini.";
RL J. Biol. Chem. 267:3257-3261(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11434514; DOI=10.1097/00008571-200106000-00011;
RA Gong Q.H., Cho J.W., Huang T., Potter C., Gholami N., Basu N.K., Kubota S.,
RA Carvalho S., Pennington M.W., Owens I.S., Popescu N.C.;
RT "Thirteen UDP-glucuronosyltransferase genes are encoded at the human UGT1
RT gene complex locus.";
RL Pharmacogenetics 11:357-368(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 98-534 (ISOFORM 2).
RA Guillemette C., Levesque E., Girard H., Bernard O.;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION (ISOFORM 2), ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=18004212; DOI=10.1097/fpc.0b013e3282f1f118;
RA Girard H., Levesque E., Bellemare J., Journault K., Caillier B.,
RA Guillemette C.;
RT "Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative
RT splicing mechanism leading to nine additional UGT1A proteins that act as
RT regulators of glucuronidation activity.";
RL Pharmacogenet. Genomics 17:1077-1089(2007).
RN [6]
RP FUNCTION (ISOFORM 1), AND CATALYTIC ACTIVITY.
RX PubMed=18674515; DOI=10.1016/j.bcp.2008.07.006;
RA Alonen A., Finel M., Kostiainen R.;
RT "The human UDP-glucuronosyltransferase UGT1A3 is highly selective towards
RT N2 in the tetrazole ring of losartan, candesartan, and zolarsartan.";
RL Biochem. Pharmacol. 76:763-772(2008).
CC -!- FUNCTION: [Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes
CC phase II biotransformation reactions in which lipophilic substrates are
CC conjugated with glucuronic acid to increase the metabolite's water
CC solubility, thereby facilitating excretion into either the urine or
CC bile (PubMed:18674515). Essential for the elimination and
CC detoxification of drugs, xenobiotics and endogenous compounds
CC (PubMed:18674515). Involved in the glucuronidation of the AGTR1
CC angiotensin receptor antagonist zolarsatan, a drug which can inhibit
CC the effect of angiotensin II (PubMed:18674515).
CC {ECO:0000269|PubMed:18674515}.
CC -!- FUNCTION: [Isoform 2]: Lacks UGT glucuronidation activity but acts as a
CC negative regulator of isoform 1. {ECO:0000269|PubMed:18004212}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glucuronate acceptor + UDP-alpha-D-glucuronate = acceptor
CC beta-D-glucuronoside + H(+) + UDP; Xref=Rhea:RHEA:21032,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:132367, ChEBI:CHEBI:132368; EC=2.4.1.17;
CC Evidence={ECO:0000269|PubMed:18674515};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC Evidence={ECO:0000305|PubMed:18674515};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=UDP-alpha-D-glucuronate + zolasartan = UDP + zolarsartan-1-N-
CC beta-D-glucuronide; Xref=Rhea:RHEA:63744, ChEBI:CHEBI:58052,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:149524, ChEBI:CHEBI:149527;
CC Evidence={ECO:0000269|PubMed:18674515};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63745;
CC Evidence={ECO:0000305|PubMed:18674515};
CC -!- SUBUNIT: Homodimer (By similarity). Homooligomer (By similarity).
CC Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8, UGT1A9
CC and UGT1A10 to form heterodimers (By similarity). Isoform 1 interacts
CC with isoform 2/i2 suggesting that oligomerization is involved in
CC negative regulation of transferase activity by isoform 2. Isoform 1
CC also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4,
CC UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 (By similarity).
CC {ECO:0000250|UniProtKB:P22309}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P22309}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=i1 {ECO:0000303|PubMed:18004212};
CC IsoId=P35504-1; Sequence=Displayed;
CC Name=2; Synonyms=i2 {ECO:0000303|PubMed:18004212}, UGT1A5s;
CC IsoId=P35504-2; Sequence=VSP_053961;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in colon and
CC small intestine. Neither isoform is expressed in liver, kidney or
CC esophagus. {ECO:0000269|PubMed:18004212}.
CC -!- MISCELLANEOUS: UGT1A5 isoform is part of the UGT1A complex locus which
CC displays alternative use of promoters, first exons and terminal exons.
CC The locus is defined by 13 first exons, which are alternatively spliced
CC to 3 other common exons and 2 alternative terminal exons 5. From the 27
CC possible mRNA isoforms, 9 produce functionally active polypeptides
CC (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1
CC (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to
CC 9 additional alternatively spliced products termed isoforms i2 and
CC which lack transferase activity. {ECO:0000269|PubMed:18004212}.
CC -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC {ECO:0000305}.
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DR EMBL; M84129; AAA61250.1; -; Genomic_DNA.
DR EMBL; M84124; AAA61247.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M84122; AAA61247.1; JOINED; Genomic_DNA.
DR EMBL; M84123; AAA61247.1; JOINED; Genomic_DNA.
DR EMBL; AF297093; AAG30421.1; -; Genomic_DNA.
DR EMBL; AC006985; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC114812; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DQ383514; ABD42927.1; -; mRNA.
DR CCDS; CCDS33404.1; -. [P35504-1]
DR PIR; B42586; B42586.
DR RefSeq; NP_061951.1; NM_019078.1. [P35504-1]
DR AlphaFoldDB; P35504; -.
DR SMR; P35504; -.
DR BioGRID; 120057; 19.
DR STRING; 9606.ENSP00000362513; -.
DR ChEMBL; CHEMBL4523985; -.
DR DrugCentral; P35504; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR GlyConnect; 1877; 2 N-Linked glycans (1 site).
DR GlyGen; P35504; 3 sites, 2 N-linked glycans (1 site).
DR iPTMnet; P35504; -.
DR PhosphoSitePlus; P35504; -.
DR BioMuta; UGT1A5; -.
DR DMDM; 549153; -.
DR jPOST; P35504; -.
DR MassIVE; P35504; -.
DR PaxDb; P35504; -.
DR PeptideAtlas; P35504; -.
DR PRIDE; P35504; -.
DR ProteomicsDB; 55073; -. [P35504-1]
DR Antibodypedia; 47694; 27 antibodies from 13 providers.
DR DNASU; 54579; -.
DR Ensembl; ENST00000373414.4; ENSP00000362513.3; ENSG00000288705.1. [P35504-1]
DR GeneID; 54579; -.
DR KEGG; hsa:54579; -.
DR MANE-Select; ENST00000373414.4; ENSP00000362513.3; NM_019078.2; NP_061951.1.
DR CTD; 54579; -.
DR DisGeNET; 54579; -.
DR GeneCards; UGT1A5; -.
DR HGNC; HGNC:12537; UGT1A5.
DR HPA; ENSG00000240224; Tissue enhanced (gallbladder, intestine, liver).
DR MalaCards; UGT1A5; -.
DR MIM; 191740; gene.
DR MIM; 606430; gene.
DR neXtProt; NX_P35504; -.
DR PharmGKB; PA37180; -.
DR VEuPathDB; HostDB:ENSG00000240224; -.
DR eggNOG; KOG1192; Eukaryota.
DR GeneTree; ENSGT00940000162976; -.
DR HOGENOM; CLU_012949_1_3_1; -.
DR InParanoid; P35504; -.
DR OMA; YMADACP; -.
DR PhylomeDB; P35504; -.
DR TreeFam; TF315472; -.
DR BRENDA; 2.4.1.17; 2681.
DR PathwayCommons; P35504; -.
DR Reactome; R-HSA-156588; Glucuronidation.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR BioGRID-ORCS; 54579; 57 hits in 908 CRISPR screens.
DR GeneWiki; UGT1A5; -.
DR GenomeRNAi; 54579; -.
DR Pharos; P35504; Tdark.
DR PRO; PR:P35504; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P35504; protein.
DR Genevisible; P35504; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IBA:GO_Central.
DR GO; GO:0015020; F:glucuronosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0052695; P:cellular glucuronidation; IBA:GO_Central.
DR CDD; cd03784; GT1_Gtf-like; 1.
DR InterPro; IPR002213; UDP_glucos_trans.
DR InterPro; IPR035595; UDP_glycos_trans_CS.
DR Pfam; PF00201; UDPGT; 1.
DR PROSITE; PS00375; UDPGT; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Membrane; Reference proteome; Signal; Transferase;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..534
FT /note="UDP-glucuronosyltransferase 1A5"
FT /id="PRO_0000036004"
FT TRANSMEM 492..508
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 348
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 436..534
FT /note="SYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQY
FT HSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH -> RKKQQSGR
FT QM (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_053961"
FT VARIANT 48
FT /note="L -> S (in dbSNP:rs3755323)"
FT /id="VAR_052455"
FT VARIANT 50
FT /note="D -> E (in dbSNP:rs3755322)"
FT /id="VAR_059845"
FT VARIANT 63
FT /note="L -> P (in dbSNP:rs3755321)"
FT /id="VAR_052456"
FT VARIANT 142
FT /note="H -> N (in dbSNP:rs3755320)"
FT /id="VAR_059846"
FT VARIANT 144
FT /note="T -> S (in dbSNP:rs28946885)"
FT /id="VAR_052457"
FT VARIANT 158
FT /note="A -> G (in dbSNP:rs12475068)"
FT /id="VAR_052458"
FT VARIANT 225
FT /note="H -> Y (in dbSNP:rs17862867)"
FT /id="VAR_052459"
FT VARIANT 249
FT /note="V -> L (in dbSNP:rs17862868)"
FT /id="VAR_052460"
FT VARIANT 259
FT /note="G -> R (in dbSNP:rs3892170)"
FT /id="VAR_052461"
SQ SEQUENCE 534 AA; 60071 MW; 05989F2A18EEFAA4 CRC64;
MATGLQVPLP QLATGLLLLL SVQPWAESGK VLVVPTDGSH WLSMREALRD LHARGHQVVV
LTLEVNMYIK EENFFTLTTY AISWTQDEFD RLLLGHTQSF FETEHLLMKF SRRMAIMNNM
SLIIHRSCVE LLHNEALIRH LHATSFDVVL TDPFHLCAAV LAKYLSIPAV FFLRNIPCDL
DFKGTQCPNP SSYIPRLLTT NSDHMTFLQR VKNMLYPLAL SYLCHAVSAP YASLASELFQ
REVSVVDLVS HASVWLFRGD FVMDYPRPIM PNMVFIGGIN CANGKPLSQE FEAYINASGE
HGIVVFSLGS MVSEIPEKKA MAIADALGKI PQTVLWRYTG TRPSNLANNT ILVKWLPQND
LLGHPMTRAF ITHAGSHGVY ESICNGVPMV MMPLFGDQMD NAKRMETKGA GVTLNVLEMT
SEDLENALKA VINDKSYKEN IMRLSSLHKD RPVEPLDLAV FWVEFVMRHK GAPHLRPAAH
DLTWYQYHSL DVIGFLLAVV LTVAFITFKC CAYGYRKCLG KKGRVKKAHK SKTH
