P0DTE4 · UD2A1_HUMAN
- ProteinUDP-glucuronosyltransferase 2A1
- GeneUGT2A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids527 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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:10359671, PubMed:18719240, PubMed:19022937, PubMed:19858781, PubMed:23288867, PubMed:23756265).
Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:10359671, PubMed:19858781, PubMed:23756265).
Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone and epitestosterone) and estrogens (estradiol and epiestriol) (PubMed:18719240, PubMed:19022937, PubMed:19858781, PubMed:23288867).
Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265).
Shows a high affinity to aliphatic odorants such as citronellol as well as olfactory tissue specificity, and therefore may be involved in olfaction (PubMed:10359671).
Shows a potential role in detoxification of toxic waste compounds in the amniotic fluid before birth, and air-born chemical after birth (PubMed:19858781).
Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:10359671, PubMed:19858781, PubMed:23756265).
Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone and epitestosterone) and estrogens (estradiol and epiestriol) (PubMed:18719240, PubMed:19022937, PubMed:19858781, PubMed:23288867).
Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265).
Shows a high affinity to aliphatic odorants such as citronellol as well as olfactory tissue specificity, and therefore may be involved in olfaction (PubMed:10359671).
Shows a potential role in detoxification of toxic waste compounds in the amniotic fluid before birth, and air-born chemical after birth (PubMed:19858781).
Miscellaneous
UGT2A1 isoform is part of the UGT2A complex locus which displays alternative use of promoters and exons. The locus is defined by 2 alternative promoters giving rise to 2 functionally active polypeptides UGT2A1 and UGT2A2. Alternative splicing of exons results in additional isoforms for each protein class.
Catalytic activity
- glucuronate acceptor + UDP-alpha-D-glucuronate = acceptor beta-D-glucuronoside + H+ + UDPThis reaction proceeds in the forward direction.
- 16beta,17beta-estriol + UDP-alpha-D-glucuronate = 16beta,17beta-estriol 16-O-(beta-D-glucuronate) + H+ + UDPThis reaction proceeds in the forward direction.
- 16alpha,17alpha-estriol + UDP-alpha-D-glucuronate = 16alpha,17alpha-estriol 16-O-(beta-D-glucuronate) + H+ + UDPThis reaction proceeds in the forward direction.
- 17alpha-estradiol + UDP-alpha-D-glucuronate = 17alpha-estradiol 17-O-(beta-D-glucuronate) + H+ + UDPThis reaction proceeds in the forward direction.
- 17alpha-estradiol + UDP-alpha-D-glucuronate = 17alpha-estradiol 3-O-(beta-D-glucuronate) + H+ + UDPThis reaction proceeds in the forward direction.
- 17beta-estradiol + UDP-alpha-D-glucuronate = 17beta-estradiol 3-O-(beta-D-glucuronate) + H+ + UDPThis reaction proceeds in the forward direction.
- 17beta-estradiol + UDP-alpha-D-glucuronate = 17beta-estradiol 17-O-(beta-D-glucuronate) + H+ + UDPThis reaction proceeds in the forward direction.
- testosterone + UDP-alpha-D-glucuronate = H+ + testosterone 17-O-(beta-D-glucuronate) + UDPThis reaction proceeds in the forward direction.
- epitestosterone + UDP-alpha-D-glucuronate = epitestosterone 17-O-(beta-D-glucuronate) + H+ + UDPThis reaction proceeds in the forward direction.
- lithocholate + UDP-alpha-D-glucuronate = H+ + lithocholoyl-3-O-(beta-D-glucuronate) + UDPThis reaction proceeds in the forward direction.
- lithocholate + UDP-alpha-D-glucuronate = lithocholoyl-24-O-(beta-D-glucuronate) + UDPThis reaction proceeds in the forward direction.
- deoxycholate + UDP-alpha-D-glucuronate = deoxycholoyl-24-O-(beta-D-glucuronate) + UDPThis reaction proceeds in the forward direction.
- hyodeoxycholate + UDP-alpha-D-glucuronate = hyodeoxycholoyl-24-O-(beta-D-glucuronate) + UDPThis reaction proceeds in the forward direction.
- hyocholate + UDP-alpha-D-glucuronate = hyocholoyl-24-O-(beta-D-glucuronate) + UDPThis reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
99 μM | 17alpha-estradiol/epiestradiol | when assaying glucuronidation position 3 | ||||
174 μM | 17beta-estradiol/estradiol | when assaying glucuronidation position 3 | ||||
36 μM | 17alpha-estradiol/epiestradiol | when assaying glucuronidation position 17 | ||||
73 μM | 17beta-estradiol/estradiol | when assaying glucuronidation position 17 | ||||
57 μM | estrone | when assaying glucuronidation position 3 | ||||
160 μM | 16alpha-hydroxyestrone | when assaying glucuronidation position 16 | ||||
38.7 μM | testosterone | when assaying glucuronidation position 17 | ||||
11.6 μM | epitestosterone | when assaying glucuronidation position 17 | ||||
251 μM | UDP-glucuronate (with 3-hydroxybiphenyl as substrate) | |||||
274 μM | UDP-glucuronate (with S---b-citronellol as substrate) | |||||
56.2 μM | testosterone | |||||
75.4 μM | 3-hydroxybiphenyl | |||||
59.5 μM | umbelliferone | |||||
51.6 μM | S---b-citronellol | |||||
170.1 μM | borneol | |||||
39.5 μM | UDP-glucuronate (with 4-methyl-umbelliferone as substrate) | |||||
303 μM | 4-nitrophenol | |||||
32.3 μM | 4-methyl-umbelliferone | |||||
0.6 μM | 4-phenylphenol | |||||
619 μM | 4-phenylphenol | |||||
2344 μM | cholate | when assaying glucuronidation position 24 | ||||
1744 μM | chenodeoxycholate | when assaying glucuronidation position 3 | ||||
1397 μM | chenodeoxycholate | when assaying glucuronidation position 24 | ||||
102.2 μM | lithocholate | when assaying glucuronidation position 3 | ||||
102.3 μM | lithocholate | when assaying glucuronidation position 24 | ||||
2405.6 μM | deoxycholate | when assaying glucuronidation position 3 | ||||
917.9 μM | deoxycholate | when assaying glucuronidation position 24 | ||||
237.4 μM | hyodeoxycholate | when assaying glucuronidation position 6 | ||||
178.5 μM | hyodeoxycholate | when assaying glucuronidation position 24 | ||||
210.7 μM | hyocholate | when assaying glucuronidation position 24 |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
693 pmol/min/mg | for the formation of 17alpha-estradiol 3-O-(beta-D-glucuronate) | ||||
128 pmol/min/mg | for the formation of 17beta-estradiol 3-O-(beta-D-glucuronate) | ||||
78.3 pmol/min/mg | for the formation of 17alpha-estradiol 17-O-(beta-D-glucuronate) | ||||
265 pmol/min/mg | for the formation of 17beta-estradiol 17-O-(beta-D-glucuronate) | ||||
57.1 pmol/min/mg | for the formation of 17alpha-estradiol 3-O-(beta-D-glucuronate) | ||||
4.6 pmol/min/mg | for the formation of 17beta-estradiol 3-O-(beta-D-glucuronate) | ||||
485 pmol/min/mg | for the formation of 17alpha-estradiol 17-O-(beta-D-glucuronate) | ||||
16.4 pmol/min/mg | for the formation of 17beta-estradiol 17-O-(beta-D-glucuronate) | ||||
263 pmol/min/mg | for the formation of 16beta,17beta-estriol 16-O-(beta-D-glucuronate) | ||||
174 pmol/min/mg | for the formation of 16alpha,17alpha-estriol 16-O-(beta-D-glucuronate) | ||||
15.8 pmol/min/mg | for the formation of 16alpha,17beta-estriol 16-O-(beta-D-glucuronate) | ||||
1.5 pmol/min/mg | for the formation of 16beta,17beta-estriol 17-O-(beta-D-glucuronate) | ||||
3.9 pmol/min/mg | for the formation of 16alpha,17alpha-estriol 3-O-(beta-D-glucuronate) | ||||
5.9 pmol/min/mg | for the formation of 16alpha,17alpha-estriol 17-O-(beta-D-glucuronate) | ||||
51 pmol/min/mg | for the formation of estrone 3-O-(beta-D-glucuronate) | ||||
210 pmol/min/mg | for the formation of 16alpha-hydroxyestrone 16-O-(beta-D-glucuronate) | ||||
427 pmol/min/mg | for the formation of testosterone 17-O-(beta-D-glucuronate) | ||||
271 pmol/min/mg | for the formation of epitestosterone 17-O-(beta-D-glucuronate) | ||||
250 pmol/min/mg | with testosterone as substrate | ||||
2600 pmol/min/mg | with 3-hydroxybiphenyl as substrate | ||||
610 pmol/min/mg | with umbelliferone as substrate | ||||
1980 pmol/min/mg | with S---b-citronellol as substrate | ||||
1050 pmol/min/mg | with borneol as substrate | ||||
141 pmol/min/mg | with 4-nitrophenol as substrate | ||||
537 pmol/min/mg | with 4-methyl-umbelliferone as substrate | ||||
116 pmol/min/mg | with 4-phenylphenol as substrate | ||||
325 pmol/min/mg | with 4-phenylphenol as substrate | ||||
83.3 pmol/min/mg | for the formation of choloyl-24-O-(beta-D-glucuronate) | ||||
95 pmol/min/mg | for the formation of chenodeoxycholoyl-3-O-(beta-D-glucuronate) | ||||
536.7 pmol/min/mg | for the formation of chenodeoxycholoyl-24-O-(beta-D-glucuronate) | ||||
685 pmol/min/mg | for the formation of lithocholoyl-3-O-(beta-D-glucuronate) | ||||
305.2 pmol/min/mg | for the formation of lithocholoyl24-O-(beta-D-glucuronate) | ||||
83.3 pmol/min/mg | for the formation of deoxycholoyl-3-O-(beta-D-glucuronate) | ||||
235.2 pmol/min/mg | for the formation of deoxycholoyl-24-O-(beta-D-glucuronate) | ||||
45.1 pmol/min/mg | for the formation of hyodeoxycholate 6-O-(beta-D-glucuronate) | ||||
805.1 pmol/min/mg | for the formation of hyocholoyl-24-O-(beta-D-glucuronate) | ||||
495.1 pmol/min/mg | for the formation of hyocholoyl-24-O-(beta-D-glucuronate) |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Molecular Function | glucuronosyltransferase activity | |
Biological Process | bile acid metabolic process | |
Biological Process | cellular glucuronidation | |
Biological Process | sensory perception of chemical stimulus | |
Biological Process | sensory perception of smell |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameUDP-glucuronosyltransferase 2A1
- EC number
- Short namesUDPGT 2A1; UGT2A1
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP0DTE4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Single-pass type I membrane protein
Endoplasmic reticulum membrane ; Single-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 21-491 | Lumenal | ||||
Sequence: GNVLIWPMEGSHWLNVKIIIDELIKKEHNVTVLVASGALFITPTSNPSLTFEIYKVPFGKERIEGVIKDFVLTWLENRPSPSTIWRFYQEMAKVIKDFHMVSQEICDGVLKNQQLMAKLKKSKFEVLVSDPVFPCGDIVALKLGIPFMYSLRFSPASTVEKHCGKVPYPPSYVPAVLSELTDQMSFTDRIRNFISYHLQDYMFETLWKSWDSYYSKALGGLLLCCPGWSAVADLGSLQPLLPGFKRFSRLSLHCSWDYRLPAGRPTTLCETMGKAEIWLIRTYWDFEFPRPYLPNFEFVGGLHCKPAKPLPKVLWRYKGKKPATLGNNTQLFDWIPQNDLLGHPKTKAFITHGGTNGIYEAIYHGVPMVGVPMFADQPDNIAHMKAKGAAVEVNLNTMTSVDLLSALRTVINEPSYKENAMRLSRIHHDQPVKPLDRAVFWIEFVMRHKGAKHLRVAAHDLTWFQYHSLDV | ||||||
Transmembrane | 492-512 | Helical | ||||
Sequence: IGFLLVCVTTAIFLVIQCCLF | ||||||
Topological domain | 513-527 | Cytoplasmic | ||||
Sequence: SCQKFGKIGKKKKRE |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_024686 | 308 | In isoform P0DTE4-1; in dbSNP:rs4148301 | |||
Sequence: G → R | ||||||
Natural variant | VAR_057326 | 391 | in dbSNP:rs4148304 | |||
Sequence: V → I |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 828 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-20 | |||||
Sequence: MLNNLLLFSLQISLIGTTLG | ||||||
Chain | PRO_0000036023 | 21-527 | UDP-glucuronosyltransferase 2A1 | |||
Sequence: GNVLIWPMEGSHWLNVKIIIDELIKKEHNVTVLVASGALFITPTSNPSLTFEIYKVPFGKERIEGVIKDFVLTWLENRPSPSTIWRFYQEMAKVIKDFHMVSQEICDGVLKNQQLMAKLKKSKFEVLVSDPVFPCGDIVALKLGIPFMYSLRFSPASTVEKHCGKVPYPPSYVPAVLSELTDQMSFTDRIRNFISYHLQDYMFETLWKSWDSYYSKALGGLLLCCPGWSAVADLGSLQPLLPGFKRFSRLSLHCSWDYRLPAGRPTTLCETMGKAEIWLIRTYWDFEFPRPYLPNFEFVGGLHCKPAKPLPKVLWRYKGKKPATLGNNTQLFDWIPQNDLLGHPKTKAFITHGGTNGIYEAIYHGVPMVGVPMFADQPDNIAHMKAKGAAVEVNLNTMTSVDLLSALRTVINEPSYKENAMRLSRIHHDQPVKPLDRAVFWIEFVMRHKGAKHLRVAAHDLTWFQYHSLDVIGFLLVCVTTAIFLVIQCCLFSCQKFGKIGKKKKRE | ||||||
Glycosylation | 49 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 313 | In isoform P0DTE4-1; N-linked (GlcNAc...) asparagine | ||||
Sequence: L | ||||||
Glycosylation | 347 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Protein-protein interaction databases
Structure
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
P0DTE4-5
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.
- Name3
- Length527
- Mass (Da)59,963
- Last updated2022-02-23 v2
- ChecksumCFC20162D2AEBBB6
P0DTE4-1
- Name1
P0DTE4-4
- Name2
- Differences from canonical
- 239-282: GGLLLCCPGWSAVADLGSLQPLLPGFKRFSRLSLHCSWDYRLPA → DGSHWLNIKIILEELIQRNHNVTVLASSATLFINSNPDSPVNFEVIPVSYKKSNIDSLIEHMIMLWIDHRPTPLTIWAFYKELGKLLDTFFQINIQLCDGVLKNPKLMARLQKGGFDVLVADPVTICGDLVALKLGIPFMYTLRFSPASTVERHCGKIPAPVSYVPAALSELTDQMTFGERIKNTISYSLQDYIFQSYWGEWNSYYSKIL
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
D6RFW5 | D6RFW5_HUMAN | UGT2A1 | 483 | ||
D6RHF3 | D6RHF3_HUMAN | UGT2A1 | 158 | ||
A0A140T9Z0 | A0A140T9Z0_HUMAN | UGT2A1 | 693 |
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 92 | in Ref. 1; CAB41974 | ||||
Sequence: L → S | ||||||
Alternative sequence | VSP_061418 | 239-282 | in isoform 2 | |||
Sequence: GGLLLCCPGWSAVADLGSLQPLLPGFKRFSRLSLHCSWDYRLPA → DGSHWLNIKIILEELIQRNHNVTVLASSATLFINSNPDSPVNFEVIPVSYKKSNIDSLIEHMIMLWIDHRPTPLTIWAFYKELGKLLDTFFQINIQLCDGVLKNPKLMARLQKGGFDVLVADPVTICGDLVALKLGIPFMYTLRFSPASTVERHCGKIPAPVSYVPAALSELTDQMTFGERIKNTISYSLQDYIFQSYWGEWNSYYSKIL | ||||||
Alternative sequence | VSP_061419 | 240-283 | in isoform 1 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_061420 | 332 | in isoform 1 | |||
Sequence: K → KEMEEFIQSSGKNGVVVFSLGSMVKNLTEEKANLIASALAQIPQK |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ006054 EMBL· GenBank· DDBJ | CAB41974.1 EMBL· GenBank· DDBJ | mRNA | ||
AK304249 EMBL· GenBank· DDBJ | BAG65116.1 EMBL· GenBank· DDBJ | mRNA | ||
AK314209 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
AC093829 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |