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Information on EC 2.7.7.4 - sulfate adenylyltransferase and Organism(s) Homo sapiens and UniProt Accession O43252
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2.7.7.4 sulfate adenylyltransferaseIUBMB Comments
The human phosphoadenosine-phosphosulfate synthase (PAPS) system is a bifunctional enzyme (fusion product of two catalytic activities). In a first step, sulfate adenylyltransferase catalyses the formation of adenosine 5'-phosphosulfate (APS) from ATP and inorganic sulfate. The second step is catalysed by the adenylylsulfate kinase portion of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase, which involves the formation of PAPS from enzyme-bound APS and ATP. In contrast, in bacteria, yeast, fungi and plants, the formation of PAPS is carried out by two individual polypeptides, sulfate adenylyltransferase (EC 2.7.7.4) and adenylyl-sulfate kinase (EC 2.7.1.25).
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- 2.7.7.4
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two-phase
- peg
- glycol
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bottom
- dextran
-
peg-rich
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liquid-liquid
-
biomolecules
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assimilatory
- vr
- chrysogenum
- k2hpo4
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diagram
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sulfotransferase
- selenate
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microfluidic
- sulfite
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counter-current
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e-cigarettes
- juncea
- o-acetylserine
- na2so4
- phytochelatins
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ultrasonic-assisted
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screw
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immiscible
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sults
- chlorate
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cigar
- agriculture
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
atps, atp sulfurylase, papss2, atp-sulfurylase, sulfurylase, atp sulphurylase, sulfate adenylyltransferase, atps2, atps1, atp-s, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
adenosine triphosphate sulfurylase
native enzyme, a dimer with each 71 kDa subunit containing an adenosine triphosphate sulfurylase and an adenosine 5'-hosphosulfate kinase domain, catalyzes the overall formation of PAPS from ATP and inorganic sulfate
PAPSS1
adenosine 5'-triphosphate sulphurylase
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adenosine 5'-triphosphate-sulfurylase
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adenosine triphosphate sulphurylase
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adenosine-5'-triphosphate sulfurylase
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adenosinetriphosphate sulfurylase
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adenylylsulfate pyrophosphorylase
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adenylyltransferase, sulfate
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ATP sulfurylase
ATP-sulfurylase
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sulfurylase
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ATP sulfurylase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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-, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
ATP:sulfate adenylyltransferase
The human phosphoadenosine-phosphosulfate synthase (PAPS) system is a bifunctional enzyme (fusion product of two catalytic activities). In a first step, sulfate adenylyltransferase catalyses the formation of adenosine 5'-phosphosulfate (APS) from ATP and inorganic sulfate. The second step is catalysed by the adenylylsulfate kinase portion of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase, which involves the formation of PAPS from enzyme-bound APS and ATP. In contrast, in bacteria, yeast, fungi and plants, the formation of PAPS is carried out by two individual polypeptides, sulfate adenylyltransferase (EC 2.7.7.4) and adenylyl-sulfate kinase (EC 2.7.1.25).
CAS REGISTRY NUMBER
COMMENTARY
9012-39-9
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
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substrate binding structure analysis, overview
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?
additional information
?
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substrate binding structure analysis, overview
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?
additional information
?
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substrate binding structure analysis, overview
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?
additional information
?
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the bifunctional PAPS synthases 1 and 2 consist of an N-terminal adenosine-5'-phosphosulphate kinase domain and a C-terminal ATP sulphurylase domain connected by a short irregular linker
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?
additional information
?
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the bifunctional PAPS synthases 1 and 2 consist of an N-terminal adenosine-5'-phosphosulphate kinase domain and a C-terminal ATP sulphurylase domain connected by a short irregular linker
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?
additional information
?
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for human PAPS synthase 1, the steady-state concentration of APS is modelled to be 0.0016 mM, but this may increase up to 0.060 mM under conditions of sulfate excess. The APS concentration for maximal APS kinase activity is 0.015 mM
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?
additional information
?
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for human PAPS synthase 1, the steady-state concentration of APS is modelled to be 0.0016 mM, but this may increase up to 0.060 mM under conditions of sulfate excess. The APS concentration for maximal APS kinase activity is 0.015 mM
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?
additional information
?
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for human PAPS synthase 1, the steady-state concentration of APS is modelled to be 0.0016 mM, but this may increase up to 0.060 mM under conditions of sulfate excess. The APS concentration for maximal APS kinase activity is 0.015 mM
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
for human PAPS synthase 1, the steady-state concentration of APS is modelled to be 0.0016 mM, but this may increase up to 0.060 mM under conditions of sulfate excess. The APS concentration for maximal APS kinase activity is 0.015 mM
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-
?
additional information
?
-
for human PAPS synthase 1, the steady-state concentration of APS is modelled to be 0.0016 mM, but this may increase up to 0.060 mM under conditions of sulfate excess. The APS concentration for maximal APS kinase activity is 0.015 mM
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-
?
additional information
?
-
-
for human PAPS synthase 1, the steady-state concentration of APS is modelled to be 0.0016 mM, but this may increase up to 0.060 mM under conditions of sulfate excess. The APS concentration for maximal APS kinase activity is 0.015 mM
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
adenylyl sulfate
APS, binding mode, overview. On the ATP sulfurylase domain that initially produces APS from sulfate and ATP, APS acts as a potent product inhibitor, being competitive with both ATP and sulfate. For the APS kinase domain that phosphorylates APS to PAPS, APS is an uncompetitive substrate inhibitor that can bind both at the ATP/ADP-binding site and the PAPS/APS-binding site
adenylyl sulfate
APS, binding mode, overview. On the ATP sulfurylase domain that initially produces APS from sulfate and ATP, APS acts as a potent product inhibitor, being competitive with both ATP and sulfate. For the APS kinase domain that phosphorylates APS to PAPS, APS is an uncompetitive substrate inhibitor that can bind both at the ATP/ADP-binding site and the PAPS/APS-binding site
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
the suppression of PAPSS1 and 2 decreases the levels of obligate cofactor and sulfate donor PAPS and reduce cellular sulfotransferase activity. Endogenous SULT2A1 is not upregulated in PAPSS1/2 double knockdown HepG2 cells, whereas the amount of UGT2B4 mRNA is significantly increased. Mechanism(s) responsible for the PAPSS1/2 knockdown-mediated upregulation of human UGT2B4, overview
metabolism
all sulfation reactions rely on active sulfate in the form of 3'-phosphoadenosine-5'-phosphosulfate (PAPS). Sulfate is converted to the sulfonucleotide adenylyl sulfate, APS, by the ubiquitous ATP sulfurylase. APS represents a metabolic branchpoint in bacteria and plants, where it is reduced by APS reductase to sulfite, and finally incorporated into primary metabolites after further reduction. Alternatively, APS is phosphorylated by APS kinase to the universal sulfate donor PAPS. In metazoans and humans, ATP sulfurylase and APS kinase reside on one polypeptide, the bifunctional PAPS synthase. All eukaryotic sulfotransferases depend on the provision of active sulfate inthe form of 3?-phospho-adenosine-5'-phosphosulfate (PAPS) for their proper action. The importance of PAPS for sulfation can rival that of ATP for phosphorylation processes. Various regulatory roles of APS in the overall process of PAPS biosynthesis
metabolism
all sulfation reactions rely on active sulfate in the form of 3'-phosphoadenosine-5'-phosphosulfate (PAPS). Sulfate is converted to the sulfonucleotide adenylyl sulfate, APS, by the ubiquitous ATP sulfurylase. APS represents a metabolic branchpoint in bacteria and plants, where it is reduced by APS reductase to sulfite, and finally incorporated into primary metabolites after further reduction. Alternatively, APS is phosphorylated by APS kinase to the universal sulfate donor PAPS. In metazoans and humans, ATP sulfurylase and APS kinase reside on one polypeptide, the bifunctional PAPS synthase. All eukaryotic sulfotransferases depend on the provision of active sulfate inthe form of 3'-phospho-adenosine-5'-phosphosulfate (PAPS) for their proper action. The importance of PAPS for sulfation can rival that of ATP for phosphorylation processes. Various regulatory roles of APS in the overall process of PAPS biosynthesis
additional information
additional information
the bifunctional PAPS synthase comprises a C-terminal ATP sulfurylase domain and an N-terminal APS kinase domain connected by a short irregular linker, no intermediate channeling by the human enzyme. The human PAPS synthases, PAPS synthase 1 (PAPSS1) and PAPS synthase 2 (PAPSS2) are bifunctional enzymes that consist of ATP sulfurylase and APS kinase domains connected by a flexible linker. Adenylyl sulfate, APS, is a highly specific stabilizer of bifunctional PAPS synthases. APS most likely stabilizes the APS kinase part of these proteins by forming a dead-end enzyme-ADP-APS complex at APS concentrations between 0.0005 and 0.005 mM. At higher concentrations, APS may bind to the catalytic centers of ATP sulfurylase
additional information
the bifunctional PAPS synthase comprises a C-terminal ATP sulfurylase domain and an N-terminal APS kinase domain connected by a short irregular linker, no intermediate channeling by the human enzyme. The human PAPS synthases, PAPS synthase 1 (PAPSS1) and PAPS synthase 2 (PAPSS2) are bifunctional enzymes that consist of ATP sulfurylase and APS kinase domains connected by a flexible linker. Adenylyl sulfate, APS, is a highly specific stabilizer of bifunctional PAPS synthases. APS most likely stabilizes the APS kinase part of these proteins by forming a dead-end enzyme-ADP-APS complex at APS concentrations between 0.0005 and 0.005 mM. At higher concentrations, APS may bind to the catalytic centers of ATP sulfurylase
additional information
-
the bifunctional PAPS synthase comprises a C-terminal ATP sulfurylase domain and an N-terminal APS kinase domain connected by a short irregular linker, no intermediate channeling by the human enzyme. The human PAPS synthases, PAPS synthase 1 (PAPSS1) and PAPS synthase 2 (PAPSS2) are bifunctional enzymes that consist of ATP sulfurylase and APS kinase domains connected by a flexible linker. Adenylyl sulfate, APS, is a highly specific stabilizer of bifunctional PAPS synthases. APS most likely stabilizes the APS kinase part of these proteins by forming a dead-end enzyme-ADP-APS complex at APS concentrations between 0.0005 and 0.005 mM. At higher concentrations, APS may bind to the catalytic centers of ATP sulfurylase
additional information
the bifunctional PAPS synthase comprises a C-terminal ATP sulfurylase domain and an N-terminal APS kinase domain connected by a short irregular linker, no intermediate channeling by the human enzyme. The human PAPS synthases, PAPS synthase 1 (PAPSS1) and PAPS synthase 2 (PAPSS2) are bifunctional enzymes that consist of ATP sulfurylase and APS kinase domains connected by a flexible linker. Adenylyl sulfate, APS, is a highly specific stabilizer of bifunctional PAPS synthases. APS most likely stabilizes the APS kinase part of these proteins by forming a dead-end enzyme-ADP-APS complex at APS concentrations between 0.0005 and 0.005 mM. At higher concentrations, APS may bind to the catalytic centers of ATP sulfurylase
additional information
the bifunctional PAPS synthase comprises a C-terminal ATP sulfurylase domain and an N-terminal APS kinase domain connected by a short irregular linker, no intermediate channeling by the human enzyme. The human PAPS synthases, PAPS synthase 1 (PAPSS1) and PAPS synthase 2 (PAPSS2) are bifunctional enzymes that consist of ATP sulfurylase and APS kinase domains connected by a flexible linker. Adenylyl sulfate, APS, is a highly specific stabilizer of bifunctional PAPS synthases. APS most likely stabilizes the APS kinase part of these proteins by forming a dead-end enzyme-ADP-APS complex at APS concentrations between 0.0005 and 0.005 mM. At higher concentrations, APS may bind to the catalytic centers of ATP sulfurylase
additional information
-
the bifunctional PAPS synthase comprises a C-terminal ATP sulfurylase domain and an N-terminal APS kinase domain connected by a short irregular linker, no intermediate channeling by the human enzyme. The human PAPS synthases, PAPS synthase 1 (PAPSS1) and PAPS synthase 2 (PAPSS2) are bifunctional enzymes that consist of ATP sulfurylase and APS kinase domains connected by a flexible linker. Adenylyl sulfate, APS, is a highly specific stabilizer of bifunctional PAPS synthases. APS most likely stabilizes the APS kinase part of these proteins by forming a dead-end enzyme-ADP-APS complex at APS concentrations between 0.0005 and 0.005 mM. At higher concentrations, APS may bind to the catalytic centers of ATP sulfurylase
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PAPS1_HUMAN
624
0
70833
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
bifunctional ATP sulfurylase/adenosine 5'-phosphosulfate kinase. Full-length enzyme and its constituent adenosine 5'-phosphosulfate kinase and ATP sulfurylase domains are individually expressed. MW is determined by SDS-PAGE for the recombinant full-length enzyme 70000 Da, for the ATP sulfurylase domain 50000 Da, and for the adenosine 5'-phosphosulfate kinase domain 22000 Da
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
the bifunctional PAPS synthase comprises a C-terminal ATP sulfurylase domain and an N-terminal APS kinase domain connected by a short irregular linker
dimer
the bifunctional PAPS synthase comprises a C-terminal ATP sulfurylase domain and an N-terminal APS kinase domain connected by a short irregular linker
additional information
additional information
native enzyme, a dimer with each 71 kDa subunit containing an adenosine triphosphate sulfurylase and an adenosine 5'-hosphosulfate kinase domain, catalyzes the overall formation of PAPS from ATP and inorganic sulfate
additional information
-
native enzyme, a dimer with each 71 kDa subunit containing an adenosine triphosphate sulfurylase and an adenosine 5'-hosphosulfate kinase domain, catalyzes the overall formation of PAPS from ATP and inorganic sulfate
additional information
-
bifunctional ATP sulfurylase/adenosine 5'-phosphosulfate kinase. Full-length enzyme and its constituent adenosine 5'-phosphosulfate kinase and ATP sulfurylase domains are individually expressed. MW is determined by SDS-PAGE for the recombinant full-length enzyme 70000 Da, for the ATP sulfurylase domain 50000 Da, and for the adenosine 5'-phosphosulfate kinase domain 22000 Da
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PAPSS1 crystal structures analysis, PDB IDs 2GIF, 2OFW, 1XNJ, and 2PEY
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
adenylyl sulfate, APS, is a highly specific stabilizer of bifunctional PAPS synthases. APS most likely stabilizes the APS kinase part of these proteins by forming a dead-end enzyme-ADP-APS complex at APS concentrations between 0.0005 and 0.005 mM. At higher concentrations, APS may bind to the catalytic centers of ATP sulfurylase
adenylyl sulfate, APS, is a highly specific stabilizer of bifunctional PAPS synthases. APS most likely stabilizes the APS kinase part of these proteins by forming a dead-end enzyme-ADP-APS complex at APS concentrations between 0.0005 and 0.005 mM. At higher concentrations, APS may bind to the catalytic centers of ATP sulfurylase
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
glutathione Sepharose column chromatography and Superdex 200 gel filtration
bifunctional ATP sulfurylase/adenosine 5'-phosphosulfate kinase. Full-length enzyme and its constituent adenosine 5'-phosphosulfate kinase and ATP sulfurylase domains are individually expressed and purified
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
isoform PAPS synthase 1 wild type and mutant proteins are expressed in Escherichia coli
bifunctional ATP sulfurylase/adenosine 5'-phosphosulfate kinase. Full-length enzyme and its constituent adenosine 5'-phosphosulfate kinase and ATP sulfurylase domains are individually expressed
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Yanagisawa, K.; Sakakibara, Y.; Suiko, M.; Takami, Y.; Nakayama, T.; Nakajima, H.; Takayanagi, K.; Natori, Y.; Liu, M.C.
cDNA cloning, expression, and characterization of the human bifunctional ATP sulfurylase/adenosine 5'-phosphosulfate kinase enzyme
Biosci. Biotechnol. Biochem.
62
1037-1040
1998
Homo sapiens
Lansdon, E.B.; Fisher, A.J.; Segel, I.H.
Human 3'-phosphoadenosine 5'-phosphosulfate synthetase (isoform 1, brain): kinetic properties of the adenosine triphosphate sulfurylase and adenosine 5'-phosphosulfate kinase domains
Biochemistry
43
4356-4365
2004
Homo sapiens (O43252), Homo sapiens
Schroeder, E.; Gebel, L.; Eremeev, A.A.; Morgner, J.; Grum, D.; Knauer, S.K.; Bayer, P.; Mueller, J.W.
Human PAPS synthase isoforms are dynamically regulated enzymes with access to nucleus and cytoplasm
PLoS ONE
7
e29559
2012
Homo sapiens (O43252), Homo sapiens
Barrett, K.G.; Fang, H.; Cukovic, D.; Dombkowski, A.A.; Kocarek, T.A.; Runge-Morris, M.
Upregulation of UGT2B4 expression by 3-phosphoadenosine-5-phosphosulfate synthase knockdown: implications for coordinated control of bile acid conjugation
Drug Metab. Dispos.
43
1061-1070
2015
Homo sapiens (O43252), Homo sapiens
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