UniProtKB - P22310 (UD14_HUMAN)
UDP-glucuronosyltransferase 1A4
UGT1A4
Functioni
UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:18177842, PubMed:24641623).
Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:18177842).
Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3 essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623).
Also glucuronidates the biologically active form of vitamin D3, calcitriol, probably leading to its biliary transport and intestinal reabsorption (PubMed:18177842).
2 PublicationsLacks UDP-glucuronosyltransferase (UGT) activity but acts as a negative regulator of isoform 1.
2 PublicationsMiscellaneous
Catalytic activityi
- EC:2.4.1.172 PublicationsThis reaction proceeds in the forward2 Publications direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
Kineticsi
- KM=6.39 µM for calcidiol (when assaying glucuronidation at position 25)1 Publication
- KM=2.16 µM for calcidiol (when assaying glucuronidation at position 3)1 Publication
- KM=4.19 µM for 5,6-trans-calcidiol (when assaying glucuronidation at position 25)1 Publication
- KM=7.3 µM for calcitriol (when assaying glucuronidation at position 25)1 Publication
- KM=10.6 µM for 17beta-estradiol/estradiol (when assaying glucuronidation at position 17)1 Publication
- KM=21.7 µM for 17alpha-estradiol/epiestradiol (when assaying glucuronidation at position 17)1 Publication
- Vmax=7.35 pmol/min/mg enzyme for the formation of calcidiol 25-O-(beta-D-glucuronate)1 Publication
- Vmax=0.93 pmol/min/mg enzyme for the formation of calcidiol 3-O-(beta-D-glucuronate)1 Publication
- Vmax=0.26 pmol/min/mg enzyme for the formation of 5,6-trans-calcidiol 25-O-(beta-D-glucuronate)1 Publication
- Vmax=33.7 pmol/min/mg enzyme for the formation of calcitriol 25-O-(beta-D-glucuronate)1 Publication
- Vmax=14 pmol/min/mg enzyme for the formation of 17beta-estradiol 17-O-(beta-D-glucuronate)1 Publication
- Vmax=41 pmol/min/mg enzyme for the formation of 17alpha-estradiol 17-O-(beta-D-glucuronate)1 Publication
- Vmax=5.5 pmol/min/mg enzyme for the formation of 16alpha,17beta-estriol 16-O-(beta-D-glucuronate)1 Publication
- Vmax=4.1 pmol/min/mg enzyme for the formation of 16alpha,17alpha-estriol 16-O-(beta-D-glucuronate)1 Publication
- Vmax=1.9 pmol/min/mg enzyme for the formation of 17beta-estradiol 17-O-(beta-D-glucuronate)1 Publication
- Vmax=6.1 pmol/min/mg enzyme for the formation of 17alpha-estradiol 17-O-(beta-D-glucuronate)1 Publication
GO - Molecular functioni
- enzyme binding Source: BHF-UCL
- glucuronosyltransferase activity Source: UniProtKB
- protein heterodimerization activity Source: BHF-UCL
- protein homodimerization activity Source: UniProtKB
GO - Biological processi
- bilirubin conjugation Source: Reactome
- cellular glucuronidation Source: UniProtKB
- flavonoid glucuronidation Source: GO_Central
- heme catabolic process Source: Reactome
- negative regulation of cellular glucuronidation Source: BHF-UCL
- negative regulation of fatty acid metabolic process Source: BHF-UCL
- negative regulation of glucuronosyltransferase activity Source: BHF-UCL
- vitamin D3 metabolic process Source: UniProtKB
- xenobiotic glucuronidation Source: GO_Central
Keywordsi
Molecular function | Glycosyltransferase, Transferase |
Biological process | Lipid metabolism |
Enzyme and pathway databases
BRENDAi | 2.4.1.17, 2681 |
PathwayCommonsi | P22310 |
Reactomei | R-HSA-156588, Glucuronidation R-HSA-189483, Heme degradation R-HSA-5579016, Defective UGT1A4 causes hyperbilirubinemia |
SABIO-RKi | P22310 |
SignaLinki | P22310 |
SIGNORi | P22310 |
Protein family/group databases
CAZyi | GT1, Glycosyltransferase Family 1 |
Chemistry databases
SwissLipidsi | SLP:000001872 |
Names & Taxonomyi
Protein namesi | Recommended name: UDP-glucuronosyltransferase 1A41 Publication (EC:2.4.1.172 Publications)Short name: UGT1A4 Alternative name(s): Bilirubin-specific UDPGT isozyme 2 Short name: hUG-BR2 UDP-glucuronosyltransferase 1-4 Short name: UDPGT 1-4 Short name: UGT1*4 Short name: UGT1-04 Short name: UGT1.4 UDP-glucuronosyltransferase 1-D Short name: UGT-1D Short name: UGT1D |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:12536, UGT1A4 |
MIMi | 606429, gene |
neXtProti | NX_P22310 |
VEuPathDBi | HostDB:ENSG00000244474 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Single-pass membrane protein Sequence analysis
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: Reactome
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 492 – 508 | HelicalSequence analysisAdd BLAST | 17 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 54657 |
MalaCardsi | UGT1A4 |
OpenTargetsi | ENSG00000244474 |
PharmGKBi | PA37179 |
Miscellaneous databases
Pharosi | P22310, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3619 |
DrugBanki | DB00321, Amitriptyline DB01217, Anastrozole DB00714, Apomorphine DB06216, Asenapine DB06401, Bazedoxifene DB05015, Belinostat DB00363, Clozapine DB14635, Curcumin sulfate DB00924, Cyclobenzaprine DB09183, Dasabuvir DB09101, Elvitegravir DB13874, Enasidenib DB11827, Ertugliflozin DB00783, Estradiol DB00977, Ethinylestradiol DB04953, Ezogabine DB11796, Fostemsavir DB09054, Idelalisib DB09262, Imidafenacin DB00555, Lamotrigine DB06077, Lumateperone DB09241, Methylene blue DB00683, Midazolam DB00334, Olanzapine DB09296, Ombitasvir DB11837, Osilodrostat DB00910, Paricalcitol DB12978, Pexidartinib DB00252, Phenytoin DB00794, Primidone DB00503, Ritonavir DB12020, Tecovirimat DB00831, Trifluoperazine DB00197, Troglitazone DB00313, Valproic acid |
DrugCentrali | P22310 |
Genetic variation databases
BioMutai | UGT1A4 |
DMDMi | 136731 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 28 | Sequence analysisAdd BLAST | 28 | |
ChainiPRO_0000036003 | 29 – 534 | UDP-glucuronosyltransferase 1A4Add BLAST | 506 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 119 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 142 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 296 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 348 | N-linked (GlcNAc...) asparagine1 Publication | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
jPOSTi | P22310 |
MassIVEi | P22310 |
MaxQBi | P22310 |
PaxDbi | P22310 |
PeptideAtlasi | P22310 |
PRIDEi | P22310 |
ProteomicsDBi | 53982 [P22310-1] 7279 |
PTM databases
GlyConnecti | 1876, 2 N-Linked glycans (1 site) |
GlyGeni | P22310, 4 sites, 2 N-linked glycans (1 site) |
iPTMneti | P22310 |
PhosphoSitePlusi | P22310 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000244474, Expressed in intestine and 43 other tissues |
Genevisiblei | P22310, HS |
Organism-specific databases
HPAi | ENSG00000244474, Tissue enriched (liver) |
Interactioni
Subunit structurei
Homodimer (PubMed:17179145). Homooligomer (Probable).
Interacts with UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 to form heterodimers (PubMed:17179145).
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, UGT1A6, UGT1A7, UGT1A8, UGT1A9 and UGT1A10 (PubMed:20610558).
1 Publication2 PublicationsGO - Molecular functioni
- enzyme binding Source: BHF-UCL
- protein heterodimerization activity Source: BHF-UCL
- protein homodimerization activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 120086, 4 interactors |
IntActi | P22310, 9 interactors |
STRINGi | 9606.ENSP00000362508 |
Chemistry databases
BindingDBi | P22310 |
Miscellaneous databases
RNActi | P22310, protein |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1192, Eukaryota |
GeneTreei | ENSGT00940000162976 |
HOGENOMi | CLU_012949_1_3_1 |
InParanoidi | P22310 |
OMAi | LLLCRVM |
OrthoDBi | 508327at2759 |
PhylomeDBi | P22310 |
TreeFami | TF315472 |
Family and domain databases
CDDi | cd03784, GT1_Gtf-like, 1 hit |
InterProi | View protein in InterPro IPR002213, UDP_glucos_trans IPR035595, UDP_glycos_trans_CS |
Pfami | View protein in Pfam PF00201, UDPGT, 1 hit |
PROSITEi | View protein in PROSITE PS00375, UDPGT, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MARGLQVPLP RLATGLLLLL SVQPWAESGK VLVVPTDGSP WLSMREALRE
60 70 80 90 100
LHARGHQAVV LTPEVNMHIK EEKFFTLTAY AVPWTQKEFD RVTLGYTQGF
110 120 130 140 150
FETEHLLKRY SRSMAIMNNV SLALHRCCVE LLHNEALIRH LNATSFDVVL
160 170 180 190 200
TDPVNLCGAV LAKYLSIPAV FFWRYIPCDL DFKGTQCPNP SSYIPKLLTT
210 220 230 240 250
NSDHMTFLQR VKNMLYPLAL SYICHTFSAP YASLASELFQ REVSVVDLVS
260 270 280 290 300
YASVWLFRGD FVMDYPRPIM PNMVFIGGIN CANGKPLSQE FEAYINASGE
310 320 330 340 350
HGIVVFSLGS MVSEIPEKKA MAIADALGKI PQTVLWRYTG TRPSNLANNT
360 370 380 390 400
ILVKWLPQND LLGHPMTRAF ITHAGSHGVY ESICNGVPMV MMPLFGDQMD
410 420 430 440 450
NAKRMETKGA GVTLNVLEMT SEDLENALKA VINDKSYKEN IMRLSSLHKD
460 470 480 490 500
RPVEPLDLAV FWVEFVMRHK GAPHLRPAAH DLTWYQYHSL DVIGFLLAVV
510 520 530
LTVAFITFKC CAYGYRKCLG KKGRVKKAHK SKTH
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_059844 | 11 | R → W. Corresponds to variant dbSNP:rs3892221Ensembl. | 1 | |
Natural variantiVAR_024684 | 24 | P → T1 PublicationCorresponds to variant dbSNP:rs6755571Ensembl. | 1 | |
Natural variantiVAR_058584 | 48 | L → V Increased glucuronosyltransferase activity towards calcidiol. 3 PublicationsCorresponds to variant dbSNP:rs2011425Ensembl. | 1 | |
Natural variantiVAR_061870 | 68 | H → Y. Corresponds to variant dbSNP:rs45621441Ensembl. | 1 | |
Natural variantiVAR_052454 | 176 | I → F. Corresponds to variant dbSNP:rs45540231Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_053960 | 436 – 534 | SYKEN…KSKTH → RKKQQSGRQM in isoform 2. 2 PublicationsAdd BLAST | 99 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M84128 Genomic DNA Translation: AAA61249.1 M84124, M84122, M84123 Genomic DNA Translation: AAA61247.1 Sequence problems. M57951 mRNA Translation: AAA63196.1 AF297093 Genomic DNA Translation: AAG30422.1 AY435139 mRNA Translation: AAR95640.1 AK313623 mRNA Translation: BAG36384.1 DQ364249 mRNA Translation: ABC96773.1 AC006985 Genomic DNA No translation available. AC114812 Genomic DNA No translation available. CH471063 Genomic DNA Translation: EAW71061.1 BC139784 mRNA Translation: AAI39785.1 |
CCDSi | CCDS33405.1 [P22310-1] |
RefSeqi | NP_009051.1, NM_007120.2 [P22310-1] |
Genome annotation databases
Ensembli | ENST00000373409; ENSP00000362508; ENSG00000244474 ENST00000450233; ENSP00000408608; ENSG00000244474 [P22310-2] |
GeneIDi | 54657 |
KEGGi | hsa:54657 |
MANE-Selecti | ENST00000373409.8; ENSP00000362508.4; NM_007120.3; NP_009051.1 |
UCSCi | uc002vux.4, human [P22310-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M84128 Genomic DNA Translation: AAA61249.1 M84124, M84122, M84123 Genomic DNA Translation: AAA61247.1 Sequence problems. M57951 mRNA Translation: AAA63196.1 AF297093 Genomic DNA Translation: AAG30422.1 AY435139 mRNA Translation: AAR95640.1 AK313623 mRNA Translation: BAG36384.1 DQ364249 mRNA Translation: ABC96773.1 AC006985 Genomic DNA No translation available. AC114812 Genomic DNA No translation available. CH471063 Genomic DNA Translation: EAW71061.1 BC139784 mRNA Translation: AAI39785.1 |
CCDSi | CCDS33405.1 [P22310-1] |
RefSeqi | NP_009051.1, NM_007120.2 [P22310-1] |
3D structure databases
SMRi | P22310 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 120086, 4 interactors |
IntActi | P22310, 9 interactors |
STRINGi | 9606.ENSP00000362508 |
Chemistry databases
BindingDBi | P22310 |
ChEMBLi | CHEMBL3619 |
DrugBanki | DB00321, Amitriptyline DB01217, Anastrozole DB00714, Apomorphine DB06216, Asenapine DB06401, Bazedoxifene DB05015, Belinostat DB00363, Clozapine DB14635, Curcumin sulfate DB00924, Cyclobenzaprine DB09183, Dasabuvir DB09101, Elvitegravir DB13874, Enasidenib DB11827, Ertugliflozin DB00783, Estradiol DB00977, Ethinylestradiol DB04953, Ezogabine DB11796, Fostemsavir DB09054, Idelalisib DB09262, Imidafenacin DB00555, Lamotrigine DB06077, Lumateperone DB09241, Methylene blue DB00683, Midazolam DB00334, Olanzapine DB09296, Ombitasvir DB11837, Osilodrostat DB00910, Paricalcitol DB12978, Pexidartinib DB00252, Phenytoin DB00794, Primidone DB00503, Ritonavir DB12020, Tecovirimat DB00831, Trifluoperazine DB00197, Troglitazone DB00313, Valproic acid |
DrugCentrali | P22310 |
SwissLipidsi | SLP:000001872 |
Protein family/group databases
CAZyi | GT1, Glycosyltransferase Family 1 |
PTM databases
GlyConnecti | 1876, 2 N-Linked glycans (1 site) |
GlyGeni | P22310, 4 sites, 2 N-linked glycans (1 site) |
iPTMneti | P22310 |
PhosphoSitePlusi | P22310 |
Genetic variation databases
BioMutai | UGT1A4 |
DMDMi | 136731 |
Proteomic databases
jPOSTi | P22310 |
MassIVEi | P22310 |
MaxQBi | P22310 |
PaxDbi | P22310 |
PeptideAtlasi | P22310 |
PRIDEi | P22310 |
ProteomicsDBi | 53982 [P22310-1] 7279 |
Protocols and materials databases
Antibodypediai | 35064, 85 antibodies from 21 providers |
DNASUi | 54657 |
Genome annotation databases
Ensembli | ENST00000373409; ENSP00000362508; ENSG00000244474 ENST00000450233; ENSP00000408608; ENSG00000244474 [P22310-2] |
GeneIDi | 54657 |
KEGGi | hsa:54657 |
MANE-Selecti | ENST00000373409.8; ENSP00000362508.4; NM_007120.3; NP_009051.1 |
UCSCi | uc002vux.4, human [P22310-1] |
Organism-specific databases
CTDi | 54657 |
DisGeNETi | 54657 |
GeneCardsi | UGT1A4 |
HGNCi | HGNC:12536, UGT1A4 |
HPAi | ENSG00000244474, Tissue enriched (liver) |
MalaCardsi | UGT1A4 |
MIMi | 606429, gene |
neXtProti | NX_P22310 |
OpenTargetsi | ENSG00000244474 |
PharmGKBi | PA37179 |
VEuPathDBi | HostDB:ENSG00000244474 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1192, Eukaryota |
GeneTreei | ENSGT00940000162976 |
HOGENOMi | CLU_012949_1_3_1 |
InParanoidi | P22310 |
OMAi | LLLCRVM |
OrthoDBi | 508327at2759 |
PhylomeDBi | P22310 |
TreeFami | TF315472 |
Enzyme and pathway databases
BRENDAi | 2.4.1.17, 2681 |
PathwayCommonsi | P22310 |
Reactomei | R-HSA-156588, Glucuronidation R-HSA-189483, Heme degradation R-HSA-5579016, Defective UGT1A4 causes hyperbilirubinemia |
SABIO-RKi | P22310 |
SignaLinki | P22310 |
SIGNORi | P22310 |
Miscellaneous databases
BioGRID-ORCSi | 54657, 5 hits in 931 CRISPR screens |
GeneWikii | UGT1A4 |
GenomeRNAii | 54657 |
Pharosi | P22310, Tbio |
PROi | PR:P22310 |
RNActi | P22310, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000244474, Expressed in intestine and 43 other tissues |
Genevisiblei | P22310, HS |
Family and domain databases
CDDi | cd03784, GT1_Gtf-like, 1 hit |
InterProi | View protein in InterPro IPR002213, UDP_glucos_trans IPR035595, UDP_glycos_trans_CS |
Pfami | View protein in Pfam PF00201, UDPGT, 1 hit |
PROSITEi | View protein in PROSITE PS00375, UDPGT, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | UD14_HUMAN | |
Accessioni | P22310Primary (citable) accession number: P22310 Secondary accession number(s): B2R937, B8K288, Q5DT00 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1991 |
Last sequence update: | August 1, 1991 | |
Last modified: | February 23, 2022 | |
This is version 208 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families