Reviewed,
UniProtKB/Swiss-Prot P19224 (UD16_HUMAN)
Last modified
July 7, 2009.
Version 90.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: UDP-glucuronosyltransferase 1-6 EC=2.4.1.17 Alternative name(s): UDP-glucuronosyltransferase 1A6 Short name=UDPGT Short name=UGT1*6 UGT1-06 Short name=UGT1.6 UGT-1F Short name=UGT1F Phenol-metabolizing UDP-glucuronosyltransferase | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 532 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at transcript level. |
General annotation (Comments)
| Function | UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. |
| Catalytic activity | UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside. |
| Subcellular location | Microsome. Endoplasmic reticulum membrane; Single-pass membrane protein Potential. |
| Tissue specificity | Expressed in skin, kidney and liver. Ref.1 |
| Polymorphism | Polymorphisms in the UGT1A6 gene define four common haplotypes: UGT1A6*1, UGT1A6*2, UGT1A6*3 and UGT1A6*4. Liver tissue samples that were homozygous for UGT1A6*2 exhibited a high rate of glucuronidation relative to tissues with other genotypes. Biochemical kinetic studies indicate that the UGT1A6*2 allozyme, expressed homozygously, had almost two-fold greater activity toward p-nitrophenol than UGT1A6*1 and when expressed heterozygously (UGT1A6*1/*2) it is associated with low enzyme activity. Common genetic variation in UGT1A6 confers functionally significant differences in biochemical phenotype. This genetic variation might impact clinical efficacy or toxicity of drugs metabolized by UGT1A6. |
| Sequence similarities | Belongs to the UDP-glycosyltransferase family. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Endoplasmic reticulum Membrane Microsome |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Signal Transmembrane |
| Molecular function | Glycosyltransferase Transferase |
| PTM | Glycoprotein |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | xenobiotic metabolic process Ref.2 Inferred from direct assay. Source: UniProtKB |
| Cellular component | endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membraneInferred from electronic annotation. Source: UniProtKB-KW microsomeNon-traceable author statement. Source: UniProtKB |
| Molecular function | glucuronosyltransferase activity Inferred from electronic annotation. Source: EC |
| Complete GO annotation... | |
Alternative products
| This entry describes 1 isoform produced by alternative splicing. [Select] Note: A number of isoforms may be produced. Isoforms have a different N-terminal domain and a common C-terminal domain of 245 residues. | ||||||
| Isoform 1 (identifier: P19224-1) 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. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 26 | 26 | Potential | ||||||
| Chain | 27 – 532 | 506 | UDP-glucuronosyltransferase 1-6 | PRO_0000036005 | |||||
Regions | |||||||||
| Transmembrane | 490 – 506 | 17 | Potential | ||||||
Amino acid modifications | |||||||||
| Glycosylation | 294 | 1 | N-linked (GlcNAc...) Potential | ||||||
| Glycosylation | 346 | 1 | N-linked (GlcNAc...) Potential | ||||||
Natural variations | |||||||||
| Natural variant | 7 | 1 | S → A in allele UGT1A6*2, allele UGT1A6*3 and allele UGT1A6*4. dbSNP rs6759892. Ref.6 | VAR_024685 | |||||
| Natural variant | 70 | 1 | S → Y: dbSNP rs1042708. Ref.1 | VAR_026628 | |||||
| Natural variant | 181 | 1 | T → A in allele UGT1A6*2. dbSNP rs2070959. Ref.6 Ref.5 | VAR_014784 | |||||
| Natural variant | 184 | 1 | R → S in allele UGT1A6*2 and allele UGT1A6*4. dbSNP rs1105879. Ref.6 Ref.5 | VAR_015559 | |||||
| Natural variant | 510 | 1 | A → P: dbSNP rs1042709. Ref.1 | VAR_026629 | |||||
Experimental info | |||||||||
| Sequence conflict | 231 | 1 | E → K in AAA61251. Ref.1 | ||||||
| Sequence conflict | 247 – 249 | 3 | YQK → SE in AAA61251. Ref.1 | ||||||
| Sequence conflict | 328 | 1 | I → N in AAA61251. Ref.1 | ||||||
| Sequence conflict | 514 | 1 | R → P in AAA61251. Ref.1 | ||||||
Sequences
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References
| [1] | "A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini." Ritter J.K., Chen F., Sheen Y.Y., Tran H.M., Kimura S., Yeatman M.T., Owens I.S. J. Biol. Chem. 267:3257-3261(1992) [PubMed: 1339448] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, VARIANTS TYR-70 AND PRO-510. |
| [2] | "Cloning and substrate specificity of a human phenol UDP-glucuronosyltransferase expressed in COS-7 cells." Harding D., Fournel-Gigleux S., Jackson M.R., Burchell B. Proc. Natl. Acad. Sci. U.S.A. 85:8381-8385(1988) [PubMed: 3141926] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. |
| [3] | "Thirteen UDP-glucuronosyltransferase genes are encoded at the human UGT1 gene complex locus." Gong Q.H., Cho J.W., Huang T., Potter C., Gholami N., Basu N.K., Kubota S., Carvalho S., Pennington M.W., Owens I.S., Popescu N.C. Pharmacogenetics 11:357-368(2001) [PubMed: 11434514] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [4] | "Aryl hydrocarbon receptor-inducible or constitutive expression of human UDP glucuronosyltransferase UGT1A6." Muenzel P.A., Lehmkoester T., Brueck M., Ritter J.K., Bock K.W. Arch. Biochem. Biophys. 350:72-78(1998) [PubMed: 9466822] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33. |
| [5] | "Genetic polymorphism in the human UGT1A6 (planar phenol) UDP-glucuronosyltransferase: pharmacological implications." Ciotti M., Marrone A., Potter C., Owens I.S. Pharmacogenetics 7:485-495(1997) [PubMed: 9429234] [Abstract] Cited for: VARIANTS ALA-181 AND SER-184. |
| [6] | "Human UGT1A6 pharmacogenetics: identification of a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissue and in cultured cells." Nagar S., Zalatoris J.J., Blanchard R.L. Pharmacogenetics 14:487-499(2004) [PubMed: 15284531] [Abstract] Cited for: VARIANTS ALA-7; ALA-181 AND SER-184. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| M84130 Genomic DNA. Translation: AAC41717.1. M84124, M84122, M84123 Genomic DNA. Translation: AAA61247.1. Sequence problems. J04093 mRNA. Translation: AAA61251.1. AF014112 Genomic DNA. Translation: AAB87411.1. AF297093 Genomic DNA. Translation: AAG30420.1. | |
| IPI | IPI00451965. |
| PIR | A31340. |
| RefSeq | NP_001063.2. |
| UniGene | Hs.554822 |
3D structure databases | |
| ModBase | Search... |
Protein family/group databases | |
| CAZy | GT1. Glycosyltransferase Family 1. |
PTM databases | |
| PhosphoSite | P19224. |
Proteomic databases | |
| PRIDE | P19224. |
Genome annotation databases | |
| Ensembl | ENSG00000167165. Homo sapiens. [Contig view] |
| GeneID | 54578. |
| KEGG | hsa:54578. |
| UCSC | uc002vuv.2. human. |
Organism-specific databases | |
| GeneCards | GC02P234217. |
| HGNC | HGNC:12538. UGT1A6. |
| MIM | 191740. gene. 606431. gene. |
| Orphanet | 205. Crigler-Najjar syndrome. 357. Gilbert syndrome. 2312. Hyperbilirubinemia transient familial neonatal. |
| PharmGKB | PA37181. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | P19224. |
| OMA | P19224. WLSMKDI. |
Enzyme and pathway databases | |
| Reactome | REACT_13433. Biological oxidations. |
Gene expression databases | |
| ArrayExpress | P19224. |
| Bgee | P19224. |
| GermOnline | ENSG00000167165. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR002213. UDP_glucos_trans. [Graphical view] |
| PANTHER | PTHR11926. UDP_glucos_trans. 1 hit. |
| Pfam | PF00201. UDPGT. 1 hit. [Graphical view] |
| PROSITE | PS00375. UDPGT. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 57086. |
| SOURCE | Search... |
Entry information
| Entry name | UD16_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P19224 Secondary accession number(s): Q96TE7 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


