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Information on EC 2.7.1.25 - adenylyl-sulfate kinase and Organism(s) Homo sapiens

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IUBMB Comments
The human phosphoadenosine-phosphosulfate synthase (PAPSS) 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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Homo sapiens
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
aps kinase, papss1, aps-kinase, paps synthetase, papss, paps synthase, adenosine-5'-phosphosulfate kinase, adenosine 5'-phosphosulfate kinase, mxan3487, adenylylsulfate kinase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3'-phosphoadenosine 5'-phosphosulfate synthetase1
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3'-phosphoadenosine-5'-phosphosulfate synthetase
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5'-phosphoadenosine sulfate kinase
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adenosine 5'-phosphosulfate kinase
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adenosine 5-phosphosulfate kinase
adenosine 5-phosphosulfate kinase is a domain of human 3-phosphoadenosine 5-phosphosulfate synthetase 1
adenosine phosphosulfate kinase
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adenosine phosphosulfokinase
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adenosine-5'-phosphosulfate 3'-phosphotransferase
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adenosine-5'-phosphosulfate-3'-phosphokinase
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adenosine-5'phosphosulfate kinase
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adenylylsulfate 3'-phosphotransferase
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adenylylsulfate kinase
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APS kinase
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ATP adenosine-5'-phosphosulfate 3'-phosphotransferase
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kinase, adenylylsulfate (phosphorylating)
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PAPS 2
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PAPS synthetase
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two isoforms, type 1 and 2
PAPSS
PAPS synthetase, two isoforms: PAPSS1 and PAPSS2
PAPSS 1
additional information
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phospho group transfer
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SYSTEMATIC NAME
IUBMB Comments
ATP:adenylyl-sulfate 3'-phosphotransferase
The human phosphoadenosine-phosphosulfate synthase (PAPSS) 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 hide
9012-38-8
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + adenosine 5'-phosphosulfate
ADP + 3'-phosphoadenosine 5'-phosphosulfate
show the reaction diagram
ATP + adenosine 5-phosphosulfate
ADP + 3'-phosphoadenosine 5'-phosphosulfate
show the reaction diagram
ATP + adenylyl sulfate
ADP + 3'-phosphoadenylyl sulfate
show the reaction diagram
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r
MgATP2- + adenylyl sulfate
MgADP- + 3'-phosphoadenylyl sulfate
show the reaction diagram
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + adenosine 5'-phosphosulfate
ADP + 3'-phosphoadenosine 5'-phosphosulfate
show the reaction diagram
ATP + adenosine 5-phosphosulfate
ADP + 3'-phosphoadenosine 5'-phosphosulfate
show the reaction diagram
PAPSS 1 is essential for the sulfonation of mucin like glycoproteins such as GlyCAM-1, CD34 and MAdCAM-1 in high endothelial venules
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NaCl
increased activity at high salt conditions, 100 mM
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
adenosine 5'-phosphosulfate
adenylyl sulfate
adenylyl sulfate acts as a strong uncompetitive inhibitor of the APS kinase reaction
NaClO3
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6.57 mM, 50% inhibition of brain PAPSS activity, 3.26 mM, 50% inhibition of liver PAPSS
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dithiothreitol
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0004 - 0.0042
adenosine 5'-phosphosulfate
0.002 - 0.0046
adenylyl sulfate
0.08 - 0.45
ATP
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.17 - 0.364
adenylyl sulfate
1.7 - 4.4
ATP
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.048
adenosine 5'-phosphosulfate
pH 8.0, 30°C
0.017 - 0.029
adenylyl sulfate
additional information
adenylyl sulfate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.12
pH 8.0. 30°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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PAPSS 1, 2a and 2b
Manually annotated by BRENDA team
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PAPSS 1
Manually annotated by BRENDA team
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PAPSS 1, 2a and 2b
Manually annotated by BRENDA team
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PAPSS 1, 2a and 2b
Manually annotated by BRENDA team
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PAPSS 1, 2a and 2b
Manually annotated by BRENDA team
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PAPSS 1, 2a and 2b
Manually annotated by BRENDA team
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PAPSS 1, 2a and 2b
Manually annotated by BRENDA team
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PAPSS 1
Manually annotated by BRENDA team
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PAPSS 1, 2a and 2b
Manually annotated by BRENDA team
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PAPSS 1, 2a and 2b
Manually annotated by BRENDA team
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PAPSS 1
Manually annotated by BRENDA team
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PAPSS 1
Manually annotated by BRENDA team
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PAPSS 1, 2a and 2b
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PAPS2_HUMAN
614
0
69501
Swiss-Prot
other Location (Reliability: 3)
PAPS1_HUMAN
624
0
70833
Swiss-Prot
other Location (Reliability: 3)
Q9UIR2_HUMAN
265
0
30142
TrEMBL
other Location (Reliability: 2)
B7Z4W3_HUMAN
159
0
17521
TrEMBL
other Location (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
150000
gel filtration
162000
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gel filtration
71000
716000
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2 * 716000, MALDI-TOF mass spectrometry, native mass by gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of the PAPSS1 APS-kinase domain in complex with APS and in complex with the products PAPS and ADP are solved, both structures of isolated domain, obtained in different crystal forms, reveal symmetrical dimers
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crystals are grown at room temperature using hanging drops containing equal volumes of protein and reservoir solution
hanging drop vapor diffusion method
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
delta34N
deletion mutant lacking the first 34 N-terminal residues from APS kinase domain results in an enzyme with similar kinetic behaviour to the full-length domain
delta50N
deletion mutant lacking the first 50 N-terminal residues from APS kinase domain show no substrate inhibition by adenylyl sulfate and approximately half of the full-length's turnover number, crystal structure reveals an asymmetrical dimer
E531Q
identified as naturally occurring mutation, E531Q found in a single sample of an African-American’s subject, almost no effect of mutations when expressed in COS-1 or HEK293 cells
G427A
G427A/H428A
no APS kinase activity
H425A
H428A
N426K
R333C
identified as naturally occurring mutation, R333C found exclusively in Caucasian-American’s DNA, almost no effect of mutations when expressed in COS-1 or HEK293 cells
R37A
mutant clone shows no substrate inhibition by adenylyl sulfate, mutant is kinetically indistinguishable from deletion mutant delta50N lacking the first N-terminal residues
R40A
mutant clone shows no substrate inhibition by adenylyl sulfate, mutant is kinetically indistinguishable from deletion mutant delta50N lacking the first N-terminal residues
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni2+-column, recombinant enzyme
protein solution is loaded on a Glutathione-Sepharose Fast Flow column and further purified by gel-filtration chromatography using Superdex 200
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protein solutions are applied on Blue-Sepharose columns and further purified by ion-exchange chromatography
recombinant enzyme using His-tag
recombinant protein using His-tag
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APS kinase domain (amino acids 25-227) of the PAPSS1 coding region are expressed as a GST-fusion protein in Escherichia coli
expressed as His-tag fusion protein in Escherichia coli BL21(DE3)
expressed in COS-1 and HEK293 cells
expression of full-length PAPS synthase and 1-268 N-terminal fragment in COS-1 cells and Escherichia coli
the APS-kinase domain (25-227 amino acid resiudes) of the PAPSS1 coding region are expressed as a GST-fusion protein in Escherichia coli BL-21
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Venkatachalam, K.V.; Akita, H.; Strott, C.A.
Molecular cloning, expression, and characterization of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase and its functional domains
J. Biol. Chem.
273
19311-19320
1998
Homo sapiens (O43252), Homo sapiens
Manually annotated by BRENDA team
Venkatachalam, K.V.; Fuda, H.; Koonin, E.V.; Strott, C.A.
Site-selected mutagenesis of a conserved nucleotide binding HXGH motif located in the ATP sulfurylase domain of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase
J. Biol. Chem.
274
2601-2604
1999
Homo sapiens (O43252), Homo sapiens
Manually annotated by BRENDA team
Xu, Z.H.; Otterness, D.M.; Freimuth, R.R.; Carlini, E.J.; Wood, T.C.; Mitchell, S.; Moon, E.; Kim, U.J.; Xu, J.P.; Siciliano, M.J.; Weinshilboum, R.M.
Human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1) and PAPSS2: gene cloning, characterization and chromosomal localization
Biochem. Biophys. Res. Commun.
268
437-444
2000
Homo sapiens
Manually annotated by BRENDA team
Fuda, H.; Shimizu, C.; Lee, Y.C.; Akita, H.; Strott, C.A.
Characterization and expression of human bifunctional 3'-phosphoadenosine 5'-phosphosulphate synthase isoforms
Biochem. J.
365
497-504
2002
Homo sapiens, Cavia porcellus (O54820)
Manually annotated by BRENDA team
Venkatachalam, K.V.
Human 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase: biochemistry, molecular biology and genetic deficiency
IUBMB Life
55
1-11
2003
Caenorhabditis elegans, Homo sapiens, Homo sapiens (O43252), Homo sapiens (O95340), Mus musculus, Cavia porcellus (O54820), Urechis caupo (Q27128), Danio rerio (Q802U9), Takifugu rubripes (Q90XY2), Drosophila melanogaster (Q9VW48)
Manually annotated by BRENDA team
Harjes, S.; Scheidig, A.; Bayer, P.
Expression, purification and crystallization of human 3'-phosphoadenosine-5'-phosphosulfate synthetase 1
Acta Crystallogr. Sect. D
60
350-352
2004
Homo sapiens
Manually annotated by BRENDA team
Xu, Z.H.; Thomae, B.A.; Eckloff, B.W.; Wieben, E.D.; Weinshilboum, R.M.
Pharmacogenetics of human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1): gene resequencing, sequence variation, and functional genomics
Biochem. Pharmacol.
65
1787-1796
2003
Homo sapiens (O43252), Homo sapiens
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
Harjes, S.; Bayer, P.; Scheidig, A.J.
The crystal structure of human PAPS synthetase 1 reveals asymmetry in substrate binding
J. Mol. Biol.
347
623-635
2005
Homo sapiens (O43252), Homo sapiens
Manually annotated by BRENDA team
Sekulic, N.; Konrad, M.; Lavie, A.
Structural mechanism for substrate inhibition of the adenosine 5-phosphosulfate kinase domain of human 3-phosphoadenosine 5-phosphosulfate synthetase 1 and its ramifications for enzyme regulation
J. Biol. Chem.
282
22112-22121
2007
Homo sapiens (O43252), Homo sapiens (O95340), Homo sapiens
Manually annotated by BRENDA team
Sekulic, N.; Dietrich, K.; Paarmann, I.; Ort, S.; Konrad, M.; Lavie, A.
Elucidation of the active conformation of the APS-kinase domain of human PAPS synthetase 1
J. Mol. Biol.
367
488-500
2007
Homo sapiens
Manually annotated by BRENDA team