Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P22310 (UD14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
UDP-glucuronosyltransferase 1-4

Short name=UDPGT 1-4
Short name=UGT1*4
Short name=UGT1-04
Short name=UGT1.4
EC=2.4.1.17
Alternative name(s):
Bilirubin-specific UDPGT isozyme 2
Short name=hUG-BR2
UDP-glucuronosyltransferase 1-D
Short name=UGT-1D
Short name=UGT1D
UDP-glucuronosyltransferase 1A4
Gene names
Name:UGT1A4
Synonyms:GNT1, UGT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length534 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein 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 glucuronidatesbilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1 By similarity.

Catalytic activity

UDP-glucuronate + acceptor = UDP + acceptor beta-D-glucuronoside.

Subunit structure

Isoform 1 interacts with isoform 2/i2suggesting 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. Ref.12

Subcellular location

Microsome. Endoplasmic reticulum membrane; Single-pass membrane protein Potential.

Tissue specificity

Isoform 1 and isoform 2 are expressed in liver, kidney, colon and small intestine. Isoform 2 but not isoform 1 is expressed in esophagus. Not expressed in skin. Ref.2 Ref.10

Induction

By phenobarbital.

Involvement in disease

Gilbert syndrome (GILBS) [MIM:143500]: Occurs as a consequence of reduced bilirubin transferase activity and is often detected in young adults with vague non-specific complaints.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Crigler-Najjar syndrome 1 (CN1) [MIM:218800]: Patients have severe hyperbilirubinemia and usually die of kernicterus (bilirubin accumulation in the basal ganglia and brainstem nuclei) within the first year of life. CN1 inheritance is autosomal recessive.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13

Crigler-Najjar syndrome 2 (CN2) [MIM:606785]: Patients have less severe hyperbilirubinemia and usually survive into adulthood without neurologic damage. Phenobarbital, which induces the partially deficient glucuronyl transferase, can diminish the jaundice. CN2 inheritance is autosomal dominant.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14 Ref.15

Miscellaneous

The gene is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.

Sequence similarities

Belongs to the UDP-glycosyltransferase family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P22310-1)

Also known as: i1;

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.
Isoform 2 (identifier: P22310-2)

Also known as: i2; UGT1A4s;

The sequence of this isoform differs from the canonical sequence as follows:
     436-534: SYKENIMRLS...VKKAHKSKTH → RKKQQSGRQM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2828 Potential
Chain29 – 534506UDP-glucuronosyltransferase 1-4
PRO_0000036003

Regions

Transmembrane492 – 50817Helical; Potential

Amino acid modifications

Glycosylation1191N-linked (GlcNAc...) Potential
Glycosylation1421N-linked (GlcNAc...) Ref.11
Glycosylation2961N-linked (GlcNAc...) Potential
Glycosylation3481N-linked (GlcNAc...) Ref.11

Natural variations

Alternative sequence436 – 53499SYKEN…KSKTH → RKKQQSGRQM in isoform 2.
VSP_053960
Natural variant111R → W.
Corresponds to variant rs3892221 [ dbSNP | Ensembl ].
VAR_059844
Natural variant241P → T. Ref.16
Corresponds to variant rs6755571 [ dbSNP | Ensembl ].
VAR_024684
Natural variant481L → V. Ref.5 Ref.16
Corresponds to variant rs2011425 [ dbSNP | Ensembl ].
VAR_058584
Natural variant681H → Y.
Corresponds to variant rs45621441 [ dbSNP | Ensembl ].
VAR_061870
Natural variant1321L → P in CN2. Ref.14
VAR_009506
Natural variant1761I → F.
Corresponds to variant rs45540231 [ dbSNP | Ensembl ].
VAR_052454
Natural variant3321Q → R in CN2. Ref.15
VAR_007710
Natural variant3761S → F in CN1. Ref.13
VAR_007711
Natural variant4871Y → D in CN2. Ref.14
VAR_009507

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (i1) [UniParc].

Last modified August 1, 1991. Version 1.
Checksum: AB745D46F57538BE

FASTA53460,025
        10         20         30         40         50         60 
MARGLQVPLP RLATGLLLLL SVQPWAESGK VLVVPTDGSP WLSMREALRE LHARGHQAVV 

        70         80         90        100        110        120 
LTPEVNMHIK EEKFFTLTAY AVPWTQKEFD RVTLGYTQGF FETEHLLKRY SRSMAIMNNV 

       130        140        150        160        170        180 
SLALHRCCVE LLHNEALIRH LNATSFDVVL TDPVNLCGAV LAKYLSIPAV FFWRYIPCDL 

       190        200        210        220        230        240 
DFKGTQCPNP SSYIPKLLTT NSDHMTFLQR VKNMLYPLAL SYICHTFSAP YASLASELFQ 

       250        260        270        280        290        300 
REVSVVDLVS YASVWLFRGD FVMDYPRPIM PNMVFIGGIN CANGKPLSQE FEAYINASGE 

       310        320        330        340        350        360 
HGIVVFSLGS MVSEIPEKKA MAIADALGKI PQTVLWRYTG TRPSNLANNT ILVKWLPQND 

       370        380        390        400        410        420 
LLGHPMTRAF ITHAGSHGVY ESICNGVPMV MMPLFGDQMD NAKRMETKGA GVTLNVLEMT 

       430        440        450        460        470        480 
SEDLENALKA VINDKSYKEN IMRLSSLHKD RPVEPLDLAV FWVEFVMRHK GAPHLRPAAH 

       490        500        510        520        530 
DLTWYQYHSL DVIGFLLAVV LTVAFITFKC CAYGYRKCLG KKGRVKKAHK SKTH 

« Hide

Isoform 2 (i2) (UGT1A4s) [UniParc].

Checksum: BB72EF2CDE4C0482
Show »

FASTA44549,802

References

« Hide 'large scale' references
[1]"Cloning of two human liver bilirubin UDP-glucuronosyltransferase cDNAs with expression in COS-1 cells."
Ritter J.K., Crawford J.M., Owens I.S.
J. Biol. Chem. 266:1043-1047(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Tissue: Liver.
[2]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Multiple variable first exons: a mechanism for cell- and tissue-specific gene regulation."
Zhang T., Haws P., Wu Q.
Genome Res. 14:79-89(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT VAL-48.
Tissue: Liver.
[6]Guillemette C., Levesque E., Girard H., Bernard O.
Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[7]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[10]"Genetic diversity at the UGT1 locus is amplified by a novel 3' alternative splicing mechanism leading to nine additional UGT1A proteins that act as regulators of glucuronidation activity."
Girard H., Levesque E., Bellemare J., Journault K., Caillier B., Guillemette C.
Pharmacogenet. Genomics 17:1077-1089(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[11]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-142 AND ASN-348.
Tissue: Liver.
[12]"Alternatively spliced products of the UGT1A gene interact with the enzymatically active proteins to inhibit glucuronosyltransferase activity in vitro."
Bellemare J., Rouleau M., Girard H., Harvey M., Guillemette C.
Drug Metab. Dispos. 38:1785-1789(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[13]"Mechanisms of inherited deficiencies of multiple UDP-glucuronosyltransferase isoforms in two patients with Crigler-Najjar syndrome, type I."
Bosma P.J., Chowdhury J.R., Huang T.-J., Lahiri P., Elferink R.P.J.O., van Es H.H.G., Lederstein M., Whitington P.F., Jansen P.L.M., Chowdhury N.R.
FASEB J. 6:2859-2863(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CN1 PHE-376.
[14]"Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase in a patient with Crigler-Najjar syndrome type II."
Aono S., Yamada Y., Keino H., Hanada N., Nakagawa T., Sasaoka Y., Yazawa T., Sato H., Koiwai O.
Biochem. Biophys. Res. Commun. 197:1239-1244(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CN2 PRO-132 AND ASP-487.
[15]"Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex that causes Crigler-Najjar syndrome type 2."
Moghrabi N., Clarke D.J., Boxer M., Burchell B.
Genomics 18:171-173(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CN2 ARG-332.
[16]"Analysis of inherited genetic variations at the UGT1 locus in the French-Canadian population."
Menard V., Girard H., Harvey M., Perusse L., Guillemette C.
Hum. Mutat. 30:677-687(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-24 AND VAL-48.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_009051.1. NM_007120.2.
UniGeneHs.554822.

3D structure databases

ProteinModelPortalP22310.
SMRP22310. Positions 284-445.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid120086. 1 interaction.
IntActP22310. 2 interactions.
STRING9606.ENSP00000362508.

Chemistry

ChEMBLCHEMBL3619.
DrugBankDB00458. Imipramine.
DB00555. Lamotrigine.
DB00910. Paricalcitol.
DB00831. Trifluoperazine.

Protein family/group databases

CAZyGT1. Glycosyltransferase Family 1.

PTM databases

PhosphoSiteP22310.

Polymorphism databases

DMDM136731.

Proteomic databases

PaxDbP22310.
PRIDEP22310.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373409; ENSP00000362508; ENSG00000244474. [P22310-1]
GeneID54657.
KEGGhsa:54657.
UCSCuc002vux.3. human. [P22310-1]

Organism-specific databases

CTD54657.
GeneCardsGC02P234627.
HGNCHGNC:12536. UGT1A4.
MIM143500. phenotype.
191740. gene.
218800. phenotype.
606429. gene.
606785. phenotype.
neXtProtNX_P22310.
PharmGKBPA37179.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1819.
HOGENOMHOG000220832.
HOVERGENHBG004033.
KOK00699.
OMALYICHAS.
OrthoDBEOG78H3T2.
PhylomeDBP22310.
TreeFamTF315472.

Enzyme and pathway databases

BioCycMetaCyc:HS11970-MONOMER.
BRENDA2.4.1.17. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKP22310.

Gene expression databases

BgeeP22310.
GenevestigatorP22310.

Family and domain databases

InterProIPR002213. UDP_glucos_trans.
[Graphical view]
PANTHERPTHR11926. PTHR11926. 1 hit.
PfamPF00201. UDPGT. 1 hit.
[Graphical view]
PROSITEPS00375. UDPGT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiUGT1A4.
GenomeRNAi54657.
NextBio57184.
PROP22310.
SOURCESearch...

Entry information

Entry nameUD14_HUMAN
AccessionPrimary (citable) accession number: P22310
Secondary accession number(s): B2R937, B8K288, Q5DT00
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: April 16, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM