ID   UD14_RABIT              Reviewed;         532 AA.
AC   Q28612;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   27-MAR-2024, entry version 104.
DE   RecName: Full=UDP-glucuronosyltransferase 1A4 {ECO:0000305};
DE            Short=UGT1A4;
DE            EC=2.4.1.17 {ECO:0000250|UniProtKB:P22310};
DE   AltName: Full=UDP-glucuronosyltransferase 1-4;
DE            Short=UDPGT 1-4;
DE            Short=UGT1*4;
DE            Short=UGT1-04;
DE            Short=UGT1.4;
DE   Flags: Precursor;
GN   Name=Ugt1a4;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=New Zealand white; TISSUE=Liver;
RA   Philipp T., Durazzo M., Trautwein C., Alex B., Johnson E.F., Straub J.G.,
RA   Straub P., Tukey R.H., Manns M.;
RL   Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: UDP-glucuronosyltransferase (UGT) that catalyzes phase II
CC       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. Essential for the elimination and detoxification of drugs,
CC       xenobiotics and endogenous compounds. Involved in the glucuronidation
CC       of calcidiol, which is the major circulating form of vitamin D3
CC       essential for the regulation of calcium and phosphate homeostasis. Also
CC       glucuronidates the biologically active form of vitamin D3, calcitriol,
CC       probably leading to its biliary transport and intestinal reabsorption.
CC       {ECO:0000250|UniProtKB:P22310}.
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:0000250|UniProtKB:P22310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21033;
CC         Evidence={ECO:0000250|UniProtKB:P22310};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=calcidiol + UDP-alpha-D-glucuronate = calcidiol 25-O-(beta-D-
CC         glucuronide) + H(+) + UDP; Xref=Rhea:RHEA:55840, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17933, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC         ChEBI:CHEBI:139277; Evidence={ECO:0000250|UniProtKB:P22310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55841;
CC         Evidence={ECO:0000250|UniProtKB:P22310};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=calcidiol + UDP-alpha-D-glucuronate = calcidiol 3-O-(beta-D-
CC         glucuronide) + H(+) + UDP; Xref=Rhea:RHEA:55844, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17933, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC         ChEBI:CHEBI:139278; Evidence={ECO:0000250|UniProtKB:P22310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55845;
CC         Evidence={ECO:0000250|UniProtKB:P22310};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=calcitriol + UDP-alpha-D-glucuronate = calcitriol 25-O-(beta-
CC         D-glucuronide) + H(+) + UDP; Xref=Rhea:RHEA:55836, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17823, ChEBI:CHEBI:58052, ChEBI:CHEBI:58223,
CC         ChEBI:CHEBI:139274; Evidence={ECO:0000250|UniProtKB:P22310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55837;
CC         Evidence={ECO:0000250|UniProtKB:P22310};
CC   -!- SUBUNIT: Homodimers. Homooligomer. Interacts with UGT1A1, UGT1A3,
CC       UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers.
CC       {ECO:0000250|UniProtKB:P22310}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:P22310}; Single-pass membrane protein
CC       {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=1;
CC         Comment=UGT1A4 is one of the isoforms produced at the UGT1A complex
CC         locus. The UGT1A complex locus produces different isoforms based on
CC         alternative use of promoters, first exons and terminal exons.
CC         {ECO:0000250|UniProtKB:P22310};
CC       Name=1;
CC         IsoId=Q28612-1; Sequence=Displayed;
CC   -!- SIMILARITY: Belongs to the UDP-glycosyltransferase family.
CC       {ECO:0000305}.
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DR   EMBL; U09101; AAA51868.1; -; mRNA.
DR   RefSeq; NP_001082791.1; NM_001089322.1. [Q28612-1]
DR   AlphaFoldDB; Q28612; -.
DR   SMR; Q28612; -.
DR   STRING; 9986.ENSOCUP00000033104; -.
DR   CAZy; GT1; Glycosyltransferase Family 1.
DR   GlyCosmos; Q28612; 2 sites, No reported glycans.
DR   GeneID; 100038310; -.
DR   KEGG; ocu:100038310; -.
DR   CTD; 100038310; -.
DR   InParanoid; Q28612; -.
DR   OrthoDB; 382054at2759; -.
DR   Proteomes; UP000001811; Unplaced.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0015020; F:glucuronosyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0052695; P:cellular glucuronidation; ISS:UniProtKB.
DR   GO; GO:0070640; P:vitamin D3 metabolic process; ISS:UniProtKB.
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   2: Evidence at transcript level;
KW   Alternative splicing; Endoplasmic reticulum; Glycoprotein;
KW   Glycosyltransferase; Lipid metabolism; Membrane; Reference proteome;
KW   Signal; Transferase; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..27
FT                   /evidence="ECO:0000255"
FT   CHAIN           28..532
FT                   /note="UDP-glucuronosyltransferase 1A4"
FT                   /id="PRO_0000036015"
FT   TRANSMEM        490..506
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   532 AA;  60489 MW;  2A594E81CC6EA672 CRC64;
     MVLGVWITLW RLVRLLLLLC VLPWAEGGKV LVVPMDGSPW LSLREVVRDV HARGHQVLVL
     GPEVTMHIKG EDFFTLQTYA TPYSKEEFDQ LMQRNYQMIF KPQHSLKTLL ETMENLKKFS
     MLCSRSCWEL LHNKPLIKHL NESSFDVVLT DPLDLCGALL AKYLSVPSVF LLRFILCDLD
     FEGTQCPNPS SYIPRMLTMN SDHMSFLQRV KNMLYPLMMK YTCHISYDPY ASLASELFQR
     EVSLVDILSH ASVWLFREDF VLDYPRPIMP NMVFIGGINC ANRKPLSQEF EAYVNASGEH
     GIVVFSLGSM VSEIPEKKAM EIADALGKIP QTVLWRYTGS RPSNLAKNTY LVKWLPQNVL
     LGHPKTRAFI THSGSHGIYE GICNGVPMVM LPLFGDQMDN AKRIETRGAG VTLNVLEMTS
     DDLANALKTV INDKSYKENI MRLSSLHKDR PVEPLDLAVF WVEFVMRHKG AAPRPAAHDL
     TWYQYHSLDV IGFLLAIVLT VAFVTFKCCA FAWGKCFGKK GRVKKAHKSK VH
//