P22310 (UD14_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	534 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate.
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 liver. Not expressed in skin or kidney. Ref.2
Induction	By phenobarbital.
Involvement in disease	Defects in UGT1A4 are the cause of Gilbert syndrome (GILBS) [MIM:143500]. Gilbert syndrome occurs as a consequence of reduced bilirubin transferase activity and is often detected in young adults with vague nonspecific complaints. Defects in UGT1A4 are the cause of Crigler-Najjar syndrome type 1 (CN1) [MIM:218800]. CN1 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. Ref.6 Defects in UGT1A4 are the cause of Crigler-Najjar syndrome type 2 (CN2) [MIM:606785]. CN2 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.
Sequence similarities	Belongs to the UDP-glycosyltransferase family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Glycosyltransferase Transferase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microsome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	enzyme binding Inferred from direct assay. Source: BHF-UCL glucuronosyltransferase activity Inferred from electronic annotation. Source: EC protein heterodimerization activity Inferred from physical interaction. Source: BHF-UCL protein homodimerization activity Inferred from physical interaction. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 1 isoform produced by alternative splicing. [Select]

Note: A number of isoforms are produced. The different isozymes have a different N-terminal domain and a common C-terminal domain of 245 residues.

Isoform 1 (identifier: P22310-1)

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 – 28	28	Potential
	Chain	29 – 534	506	UDP-glucuronosyltransferase 1-4		PRO_0000036003
Regions
	Transmembrane	492 – 508	17	Helical; Potential
Amino acid modifications
	Glycosylation	119	1	N-linked (GlcNAc...) Potential
	Glycosylation	142	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	296	1	N-linked (GlcNAc...) Potential
	Glycosylation	348	1	N-linked (GlcNAc...) Ref.5
Natural variations
	Natural variant	11	1	R → W. Corresponds to variant rs3892221 [ dbSNP | Ensembl ].		VAR_059844
	Natural variant	24	1	P → T. Ref.9 Corresponds to variant rs6755571 [ dbSNP | Ensembl ].		VAR_024684
	Natural variant	48	1	L → V. Ref.4 Ref.9 Corresponds to variant rs2011425 [ dbSNP | Ensembl ].		VAR_058584
	Natural variant	68	1	H → Y. Corresponds to variant rs45621441 [ dbSNP | Ensembl ].		VAR_061870
	Natural variant	132	1	L → P in CN2. Ref.7		VAR_009506
	Natural variant	176	1	I → F. Corresponds to variant rs45540231 [ dbSNP | Ensembl ].		VAR_052454
	Natural variant	332	1	Q → R in CN2. Ref.8		VAR_007710
	Natural variant	376	1	S → F in CN1. Ref.6		VAR_007711
	Natural variant	487	1	Y → D in CN2. Ref.7		VAR_009507

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 1, 1991. Version 1. Checksum: AB745D46F57538BE	FASTA	534	60,025
	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

References

	« Hide 'large scale' referencesShow '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: 1898728] [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: 1339448] [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: 11434514] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-48. Tissue: Liver.
[5]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-142 AND ASN-348, MASS SPECTROMETRY. Tissue: Liver.
[6]	"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: 1634050] [Abstract] Cited for: VARIANT CN1 PHE-376.
[7]	"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: 8280139] [Abstract] Cited for: VARIANTS CN2 PRO-132 AND ASP-487.
[8]	"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: 8276413] [Abstract] Cited for: VARIANT CN2 ARG-332.
[9]	"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: 19204906] [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. AK313623 mRNA. Translation: BAG36384.1.
IPI	IPI00439935.
RefSeq	NP_009051.1. NM_007120.2.
UniGene	Hs.554822.
3D structure databases
ProteinModelPortal	P22310.
SMR	P22310. Positions 282-450.
ModBase	Search...
Protein-protein interaction databases
IntAct	P22310. 1 interaction.
STRING	P22310.
Protein family/group databases
CAZy	GT1. Glycosyltransferase Family 1.
PTM databases
PhosphoSite	P22310.
Polymorphism databases
DMDM	136731.
Proteomic databases
PRIDE	P22310.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000373409; ENSP00000362508; ENSG00000244474.
GeneID	54657.
KEGG	hsa:54657.
UCSC	uc002vux.1. human.
Organism-specific databases
CTD	54657.
GeneCards	GC02P234627.
HGNC	HGNC:12536. UGT1A4.
MIM	143500. phenotype. 191740. gene. 218800. phenotype. 606429. gene. 606785. phenotype.
neXtProt	NX_P22310.
PharmGKB	PA37179.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG004033.
OrthoDB	EOG45B1FF.
PhylomeDB	P22310.
Enzyme and pathway databases
BioCyc	MetaCyc:54657-MONOMER.
BRENDA	2.4.1.17. 2681.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P22310.
Genevestigator	P22310.
GermOnline	ENSG00000167165. Homo sapiens.
Family and domain databases
InterPro	IPR002213. UDP_glucos_trans. [Graphical view]
KO	K00699.
PANTHER	PTHR11926. UDP_glucos_trans. 1 hit.
Pfam	PF00201. UDPGT. 1 hit. [Graphical view]
PROSITE	PS00375. UDPGT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00458. Imipramine. DB00555. Lamotrigine. DB00910. Paricalcitol. DB00831. Trifluoperazine.
NextBio	57184.
SOURCE	Search...

Entry information

Entry name

UD14_HUMAN

Accession

Primary (citable) accession number: P22310
Secondary accession number(s): B2R937

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	August 1, 1991
Last modified:	January 25, 2012
This is version 121 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.