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   27-MAR-2024, entry version 188.
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   GlyCosmos; P35504; 3 sites, 2 glycans.
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; 9606-ENSP00000362513; -.
DR   PeptideAtlas; P35504; -.
DR   Antibodypedia; 47694; 29 antibodies from 14 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   AGR; HGNC:12537; -.
DR   CTD; 54579; -.
DR   DisGeNET; 54579; -.
DR   GeneCards; UGT1A5; -.
DR   HGNC; HGNC:12537; UGT1A5.
DR   HPA; ENSG00000288705; 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; KYFCHIS; -.
DR   OrthoDB; 382054at2759; -.
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 970 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:0019899; F:enzyme binding; IBA:GO_Central.
DR   GO; GO:0015020; F:glucuronosyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046982; F:protein heterodimerization activity; IEA:UniProt.
DR   GO; GO:0042803; F:protein homodimerization activity; IEA:UniProt.
DR   GO; GO:0052695; P:cellular glucuronidation; IBA:GO_Central.
DR   CDD; cd03784; GT1_Gtf-like; 1.
DR   Gene3D; 3.40.50.2000; Glycogen Phosphorylase B; 2.
DR   InterPro; IPR002213; UDP_glucos_trans.
DR   InterPro; IPR035595; UDP_glycos_trans_CS.
DR   PANTHER; PTHR48043; EG:EG0003.4 PROTEIN-RELATED; 1.
DR   PANTHER; PTHR48043:SF157; UDP GLUCURONOSYLTRANSFERASE 1 FAMILY POLYPEPTIDE A3 PRECURSOR-RELATED; 1.
DR   Pfam; PF00201; UDPGT; 1.
DR   SUPFAM; SSF53756; UDP-Glycosyltransferase/glycogen phosphorylase; 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
//