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MetaCyc Enzyme: sulfotransferase 1A3/1A4

Gene: SULT1A3 Accession Number: HS05608 (MetaCyc)

Synonyms: TL-PST, STM, sulfotransferase, monoamine-preferring, thermolabile phenol sulfotransferase, M-PST, placental estrogen sulfotransferase, catecholamine-sulfating phenol sulfotransferase, HAST3, sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3

Species: Homo sapiens

Subunit composition of sulfotransferase 1A3/1A4 = [SULT1A3]2
         sulfotransferase 1A3/1A4 monomer = SULT1A3

Summary:
This enzyme is a member of the SULT enzyme family, and the SULT1 (phenol sulfotransferase) subfamily. It is widely expressed in tissues, including liver, intestine and brain. In humans, sulfation modulates the activity and facilitates the transport of catecholamines and other biogenic amines. SULT1A3 prefers endogenous catecholamines as substrates and is highly expressed in the gastrointestinal tract (in [Dajani98]). Sulfation is a major metabolic detoxification mechanism [Dajani99]. The crystal structure of this enzyme has been reported [Bidwell99, Lu05a].

The enzyme has been purified from human brain [Whittemore85]. Recombinant enzyme from brain cDNA has been expressed in COS-7 cells [Whittemore85], recombinant enzyme from breast carcinoma T47D cell cDNA has been expressed in Escherichia coli [Ganguly95], recombinant enzyme from liver cDNA has been expressed in Escherichia coli [Dajani98], and recombinant enzyme from platelet cDNA has been expressed in Saccharomyces cerevisiae, COS-7 and V79 cells [Dajani99]. It was also expressed in Escherichia coli and purified. [Dajani99]. The molecular mass of the native dimeric enzyme was determined by a combination of dynamic light scattering, and sedimentation equilibrium experiments [Dajani99].

There is evidence that the SULT1A3 gene is duplicated [Hildebrandt04].

Citations: [Jones95, Pai03, Glatt00a, Wood94, Glatt01, Weinshilboum97, Bernier94, Aksoy94, Pai02, Glatt00, Zhu93]

Map Position: [30,526,347 -> 30,536,777] (33.47 centisomes)

Molecular Weight of Polypeptide: 34 kD (experimental) [Dajani99 ]

Molecular Weight of Multimer: 68 kD (experimental) [Dajani99]

Unification Links: ArrayExpress:P50224 , DisProt:DP00011 , Entrez-gene:6818 , Entrez-gene:79008 , PhosphoSite:P50224 , PhylomeDB:P50224 , Pride:P50224 , Protein Model Portal:P50224 , SMR:P50224 , String:9606.ENSP00000339221 , UniProt:P50224

Relationship Links: InterPro:IN-FAMILY:IPR000863 , InterPro:IN-FAMILY:IPR027417 , PDB:Structure:1CJM , PDB:Structure:2A3R , Pfam:IN-FAMILY:PF00685

Gene-Reaction Schematic: ?


Enzymatic reaction of: serotonin sulfotransferase (sulfotransferase 1A3/1A4)

serotonin + 3'-phosphoadenylyl-sulfate <=> adenosine 3',5'-bisphosphate + serotonin O-sulfate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: serotonin degradation

Summary:
It has been shown that purified, recombinant SULT1A1, SULT1A3 and SULT1C#2 isoforms had differential sulfating activities toward serotonin, dopamine, L-dopa and their hydroxylated derivatives [Yasuda07].

Kinetic Parameters:

Substrate
Km (μM)
Citations
serotonin
132.6
[Yasuda07]


Enzymatic reaction of: dopamine sulfotransferase (sulfotransferase 1A3/1A4)

dopamine + 3'-phosphoadenylyl-sulfate <=> adenosine 3',5'-bisphosphate + dopamine 3-O-sulfate + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

Alternative Substrates for dopamine: acetaminophen [Whittemore85 ] , minoxidil [Whittemore85 ] , 3,4-dihydroxybenzylamine [Whittemore85 ] , 6-hydroxydopamine [Whittemore85 ] , 4-methoxytyramine [Whittemore85 ] , serotonin [Whittemore85 ] , octopamine [Whittemore85 ] , 1-naphthol [Ganguly95 ] , 4-nitrophenol [Ganguly95 ]

In Pathways: dopamine degradation

Summary:
The kinetic constants are for the enzyme purified directly from human brain. Sulfation proceeds in an ordered, bisubstrate reaction mechanism with PAPS as the leading substrate [Whittemore85]. The enzyme has been reported to undergo substrate inhibition by dopamine [Barnett04].

The enzyme also has a unique D-dopa/D-tyrosine-sulfating activity stimulated by Mn2+ [Pai03].

Inhibitors (Competitive): ATP [Whittemore85]

Inhibitors (Other): adenosine 3',5'-bisphosphate [Whittemore85]

Kinetic Parameters:

Substrate
Km (μM)
Citations
dopamine
2.9
[Whittemore85]
3'-phosphoadenylyl-sulfate
0.35
[Whittemore85]

pH(opt): 7.0 [Whittemore85]


References

Aksoy94: Aksoy IA, Callen DF, Apostolou S, Her C, Weinshilboum RM (1994). "Thermolabile phenol sulfotransferase gene (STM): localization to human chromosome 16p11.2." Genomics 23(1);275-7. PMID: 7829089

Barnett04: Barnett AC, Tsvetanov S, Gamage N, Martin JL, Duggleby RG, McManus ME (2004). "Active site mutations and substrate inhibition in human sulfotransferase 1A1 and 1A3." J Biol Chem 279(18);18799-805. PMID: 14871892

Bernier94: Bernier F, Lopez Solache I, Labrie F, Luu-The V (1994). "Cloning and expression of cDNA encoding human placental estrogen sulfotransferase." Mol Cell Endocrinol 99(1);R11-5. PMID: 8187949

Bidwell99: Bidwell LM, McManus ME, Gaedigk A, Kakuta Y, Negishi M, Pedersen L, Martin JL (1999). "Crystal structure of human catecholamine sulfotransferase." J Mol Biol 293(3);521-30. PMID: 10543947

Dajani98: Dajani R, Hood AM, Coughtrie MW (1998). "A single amino acid, glu146, governs the substrate specificity of a human dopamine sulfotransferase, SULT1A3." Mol Pharmacol 54(6);942-8. PMID: 9855620

Dajani99: Dajani R, Sharp S, Graham S, Bethell SS, Cooke RM, Jamieson DJ, Coughtrie MW (1999). "Kinetic properties of human dopamine sulfotransferase (SULT1A3) expressed in prokaryotic and eukaryotic systems: comparison with the recombinant enzyme purified from Escherichia coli." Protein Expr Purif 16(1);11-8. PMID: 10336855

Ganguly95: Ganguly TC, Krasnykh V, Falany CN (1995). "Bacterial expression and kinetic characterization of the human monoamine-sulfating form of phenol sulfotransferase." Drug Metab Dispos 23(9);945-50. PMID: 8565785

Glatt00: Glatt H (2000). "Sulfotransferases in the bioactivation of xenobiotics." Chem Biol Interact 129(1-2);141-70. PMID: 11154739

Glatt00a: Glatt H, Engelke CE, Pabel U, Teubner W, Jones AL, Coughtrie MW, Andrae U, Falany CN, Meinl W (2000). "Sulfotransferases: genetics and role in toxicology." Toxicol Lett 112-113;341-8. PMID: 10720750

Glatt01: Glatt H, Boeing H, Engelke CE, Ma L, Kuhlow A, Pabel U, Pomplun D, Teubner W, Meinl W (2001). "Human cytosolic sulphotransferases: genetics, characteristics, toxicological aspects." Mutat Res 482(1-2);27-40. PMID: 11535246

Hildebrandt04: Hildebrandt MA, Salavaggione OE, Martin YN, Flynn HC, Jalal S, Wieben ED, Weinshilboum RM (2004). "Human SULT1A3 pharmacogenetics: gene duplication and functional genomic studies." Biochem Biophys Res Commun 321(4);870-8. PMID: 15358107

Jones95: Jones AL, Hagen M, Coughtrie MW, Roberts RC, Glatt H (1995). "Human platelet phenolsulfotransferases: cDNA cloning, stable expression in V79 cells and identification of a novel allelic variant of the phenol-sulfating form." Biochem Biophys Res Commun 208(2);855-62. PMID: 7695643

Lu05a: Lu JH, Li HT, Liu MC, Zhang JP, Li M, An XM, Chang WR (2005). "Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3'-phosphoadenosine 5'-phosphate." Biochem Biophys Res Commun 335(2);417-23. PMID: 16083857

Pai02: Pai TG, Ohkimoto K, Sakakibara Y, Suiko M, Sugahara T, Liu MC (2002). "Manganese stimulation and stereospecificity of the Dopa (3,4-dihydroxyphenylalanine)/tyrosine-sulfating activity of human monoamine-form phenol sulfotransferase. Kinetic studies of the mechanism using wild-type and mutant enzymes." J Biol Chem 277(46);43813-20. PMID: 12228221

Pai03: Pai TG, Oxendine I, Sugahara T, Suiko M, Sakakibara Y, Liu MC (2003). "Structure-function relationships in the stereospecific and manganese-dependent 3,4-dihydroxyphenylalanine/tyrosine-sulfating activity of human monoamine-form phenol sulfotransferase, SULT1A3." J Biol Chem 278(3);1525-32. PMID: 12424257

Weinshilboum97: Weinshilboum RM, Otterness DM, Aksoy IA, Wood TC, Her C, Raftogianis RB (1997). "Sulfation and sulfotransferases 1: Sulfotransferase molecular biology: cDNAs and genes." FASEB J 11(1);3-14. PMID: 9034160

Whittemore85: Whittemore RM, Pearce LB, Roth JA (1985). "Purification and kinetic characterization of a dopamine-sulfating form of phenol sulfotransferase from human brain." Biochemistry 24(10);2477-82. PMID: 3860259

Wood94: Wood TC, Aksoy IA, Aksoy S, Weinshilboum RM (1994). "Human liver thermolabile phenol sulfotransferase: cDNA cloning, expression and characterization." Biochem Biophys Res Commun 198(3);1119-27. PMID: 8117269

Yasuda07: Yasuda S, Liu MY, Suiko M, Sakakibara Y, Liu MC (2007). "Hydroxylated serotonin and dopamine as substrates and inhibitors for human cytosolic SULT1A3." J Neurochem. PMID: 17908235

Zhu93: Zhu X, Veronese ME, Bernard CC, Sansom LN, McManus ME (1993). "Identification of two human brain aryl sulfotransferase cDNAs." Biochem Biophys Res Commun 195(1);120-7. PMID: 8363592


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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