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Information on EC 2.8.2.20 - protein-tyrosine sulfotransferase and Organism(s) Homo sapiens and UniProt Accession O60507

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     2 Transferases
         2.8 Transferring sulfur-containing groups
             2.8.2 Sulfotransferases
                2.8.2.20 protein-tyrosine sulfotransferase
IUBMB Comments
The tyrosine residues of some specific proteins of rat pheochromocytoma cells act as acceptors.
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This record set is specific for:
Homo sapiens
UNIPROT: O60507
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
tyrosylprotein sulfotransferase, tpst2, tpst-1, tpst1, tpst-2, tyrosylprotein sulfotransferase 2, tpst-a, tyrosylprotein sulfotransferase-1, tyrosylprotein sulfotransferase 1, tyrosylprotein sulfotransferase-2, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TPST-1
TPST1
tyrosylprotein sulfotransferase 1
-
tyrosylprotein sulfotransferase-1
-
tyrosylprotein sulfotransferases 1
-
sulfotransferase, protein (tyrosine)
-
-
-
-
TPST-1
-
-
TPST-2
TPST1
TPST2
tyrosylprotein sulfotransferase
tyrosylprotein sulfotransferase 2
-
-
tyrosylprotein sulfotransferase-2
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
3'-phosphoadenylyl sulfate + protein tyrosine = adenosine 3',5'-bisphosphate + protein tyrosine-O-sulfate
show the reaction diagram
catalytic mechanism, structure-function analysis
3'-phosphoadenylyl sulfate + protein tyrosine = adenosine 3',5'-bisphosphate + protein tyrosine-O-sulfate
show the reaction diagram
enzymatic mechanism and structure-function relationships, overview. The catalytic mechanism follows the sequential steps: binding of PAPS, binding of the target protein, sulfate transfer, release of the sulfated target and release of 3',5'-ADP
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
sulfate group transfer
SYSTEMATIC NAME
IUBMB Comments
3'-phosphoadenylyl-sulfate:protein-tyrosine O-sulfotransferase
The tyrosine residues of some specific proteins of rat pheochromocytoma cells act as acceptors.
CAS REGISTRY NUMBER
COMMENTARY hide
87588-33-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenylyl sulfate + benzyl-Glu-Tyr
adenosine 3',5'-bisphosphate + benzyl-Glu-Tyr-O-sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + C4P5Y5 peptide
adenosine 3',5'-bisphosphate + sulfated C4P5Y5 peptide
show the reaction diagram
a C4 complement derived peptide substrate, sulfation of the Tyr741 residue
-
-
?
3'-phosphoadenylyl sulfate + CXC-chemokine receptor 4
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
3'-phosphoadenylyl sulfate + CXCR4 1-38
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
CC-chemokine receptor 4 peptide, amino acids 1-38
the enzyme has a strong site preference for sulfation of Tyr-21 over Tyr-7 and Tyr-12, sulfation of Tyr-21 is required for high-affinity interaction with stromal cell-derived factor-1 (SDF-1alpha)
-
?
3'-phosphoadenylyl sulfate + EDFEDYEFDG
adenosine 3',5'-bisphosphate + EDFEDY(sulfated)EFDG
show the reaction diagram
GST-tagged CC4-tide, peptide 5-FAM-EDFEDYEFDG-CONH2, from human complement C4 protein
-
-
?
3'-phosphoadenylyl sulfate + EDYDTTTEFDsYGD
adenosine 3',5'-bisphosphate + EDsYDTTTEFDsYGD
show the reaction diagram
G protein-coupled receptor, human chemokine receptor 1, amino acids 8-20
-
-
?
3'-phosphoadenylyl sulfate + EDYDTTTEFDYGD
adenosine 3',5'-bisphosphate + EDYDTTTEFDsYGD
show the reaction diagram
G protein-coupled receptor human chemokine receptor 1, amino acids 8-20
-
-
?
3'-phosphoadenylyl sulfate + ENYSYDLDYYS
adenosine 3',5'-bisphosphate + ENsYSsYDLDsYsYS
show the reaction diagram
G protein-coupled receptor human gpr1, amino acids 13-23, sulfation order: first Tyr21, second Tyr22, third Tyr15 or 17, fourth Tyr 15 or 17
-
-
?
3'-phosphoadenylyl sulfate + ERHTRSYDYMEGGD
adenosine 3',5'-bisphosphate + ERHTRSYDY(sulfated)MEGGD
show the reaction diagram
FGF7-tide, peptide 5-FAM-ERHTRSYDYMEGGD-CONH2, from fibroblast growth factor 7
-
-
?
3'-phosphoadenylyl sulfate + gastrin peptide
adenosine 3',5'-bisphosphate + sulfated gastrin peptide
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + P-selectin glycoprotein ligand-1
?
show the reaction diagram
recombinantly expressed substrate PSGL-1, glycoprotein found on the plasma membrane of neutrophils or monocytes. TPST activity on GST-tagged PSGL-1 is not affected by the GST fusion tag
-
-
?
3'-phosphoadenylyl sulfate + peptide Y+1 tyrosine
adenosine 3',5'-bisphosphate + peptide Y+1 tyrosine-O-sulfate
show the reaction diagram
i.e. peptide Glu-Leu-Asp-Tyr-Dap-Gly-Glu-Ala
-
-
?
3'-phosphoadenylyl sulfate + protein tyrosine
adenosine 3',5'-bisphosphate + protein tyrosine-O-sulfate
show the reaction diagram
3'-phosphoadenylyl sulfate + PSGL-1
adenosine 3',5'-bisphosphate + PSGL-1 sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + PSGL-1 1-15 peptide
adenosine 3',5'-bisphosphate + sulfated PSGL-1 1-15 peptide
show the reaction diagram
QATEYEYLDYDFLPE-NH2
-
-
?
3'-phosphoadenylyl sulfate + QATEYEYLDYDFLPE
adenosine 3',5'-bisphosphate + QATEsYEsYLDsYDFLPE
show the reaction diagram
human PSGL-1, amino acids 42-56, sulfation order: first Tyr51, second Tyr46 or 48, third Tyr46 or 48
-
-
?
3'-phosphoadenylyl sulfate + QATEYEYLDYDFLPE-NH2
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
P-selectin glycoprotein ligand-1, amino acids 1-15
-
-
?
3'-phosphoadenylyl sulfate + SYGDEYPDYLD
adenosine 3',5'-bisphosphate + SsYGDEsYPDsYLD
show the reaction diagram
G protein-coupled receptor human dez, amino acids 13-23, sulfation order: first Tyr21, second Tyr18, third Tyr14
-
-
?
3'-phosphoadenylyl sulfate + TEYEYLDYDFLPETE
adenosine 3',5'-bisphosphate + TEYEYLDY(sulfated)DFLPETE
show the reaction diagram
PSGL1-tide, peptide 5-FAM-TEYEYLDYDFLPETE-CONH2, from P-selectin glycoprotein ligand-1
-
-
?
3'-phosphoadenylyl sulfate + TTFFDsYDYGA
adenosine 3',5'-bisphosphate + TTFFDsYDsYGA
show the reaction diagram
G protein-coupled receptor, human chemokine receptor 2, amino acids 21-30
-
-
?
3'-phosphoadenylyl sulfate + TTFFDYDsYGA
adenosine 3',5'-bisphosphate + TTFFDsYDsYGA
show the reaction diagram
G protein-coupled receptor, human chemokine receptor 2, amino acids 21-30
-
-
?
3'-phosphoadenylyl sulfate + TTFFDYDYGA
adenosine 3',5'-bisphosphate + TTFFDsYDYGA
show the reaction diagram
G protein-coupled receptor, human chemokine receptor 2, amino acids 21-30
-
-
?
3'-phosphoadenylyl sulfate + TTFFDYDYGA
adenosine 3',5'-bisphosphate + TTFFDYDsYGA
show the reaction diagram
G protein-coupled receptor, human chemokine receptor 2, amino acids 21-30
-
-
?
3'-phosphoadenylyl sulfate + TTVTDYYYPDIFSS
adenosine 3',5'-bisphosphate + TTVTDY(sulfated)YYPDIFSS
show the reaction diagram
CCR8-tide, peptide 5-FAM-TTVTDYYYPDIFSS-CONH2, from C-C motif chemokine receptor 8
-
-
?
3'-phosphoadenylyl sulfate + Tyr-Tyr-Tyr
adenosine 3',5'-bisphosphate + Tyr-Tyr-Tyr-O-sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + vitronectin peptide
adenosine 3',5'-bisphosphate + vitronectin-O-sulfate
show the reaction diagram
amino acids 75-91, Y(SO3H)TVY(SO3H)DDGEEKNDATVHE
-
-
?
3'-phosphoadenylyl sulfate + VTDsYsYYPDI
adenosine 3',5'-bisphosphate + VTDsYsYsYPDI
show the reaction diagram
Tyr16-sulfated G protein-coupled receptor CCR8, amino acids 12-20
-
-
?
3'-phosphoadenylyl sulfate + VTDsYYsYPDI
adenosine 3',5'-bisphosphate + VTDsYsYsYPDI
show the reaction diagram
CC-chemokine receptor 8 nonapeptide, sY15CCR8
-
-
?
3'-phosphoadenylyl sulfate + VTDsYYYPDG
adenosine 3',5'-bisphosphate + VTDsYYsYPDI
show the reaction diagram
CC-chemokine receptor 8 nonapeptide, sY15sY17CCR8
-
-
?
3'-phosphoadenylyl sulfate + VTDsYYYPDI
adenosine 3',5'-bisphosphate + VTDsYYsYPDI
show the reaction diagram
CC-chemokine receptor 8 nonapeptide, amino acids 12-20
-
-
?
3'-phosphoadenylyl sulfate + VTDYsYYPDI
adenosine 3',5'-bisphosphate + VTDsYsYYPDI
show the reaction diagram
Tyr16-sulfated G protein-coupled receptor CCR8, amino acids 12-20
-
-
?
3'-phosphoadenylyl sulfate + VTDYYsYPDI
adenosine 3',5'-bisphosphate + VTDsYYsYPDI
show the reaction diagram
both isoenzymes sequentially sulfate the CCR8 peptide such that Tyr15 is sulfated first followed by Tyr17 sulfation
-
-
?
3'-phosphoadenylyl sulfate + VTDYYYPDI
adenosine 3',5'-bisphosphate + VTDsYYYPDI
show the reaction diagram
non CC-chemokine receptor 8
-
-
?
3'-phosphoadenylyl sulfate + VTDYYYPDI
adenosine 3',5'-bisphosphate + VTDYYsYPDI
show the reaction diagram
a peptide modeled on the N-terminal extracellular domain of human CCR8, amino acids 12-20
-
-
?
3'-phosphoadenylyl sulfate + [PSGL-1 peptide]-L-tyrosine
adenosine 3',5'-bisphosphate + [PSGL-1 peptide]-L-tyrosine-O-sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + [Y+3 peptide]-L-tyrosine
adenosine 3',5'-bisphosphate + [Y+3 peptide]-L-tyrosine-O-sulfate
show the reaction diagram
i.e. biotin-RDRRQATEYEYLDYDFLPETEPPP
-
-
?
3'-phosphoadenylylsulfate + QATEYEYLDYDFLPEC
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
derived from N-terminal residues of the mature leukocyte adhesion molecule P-selectin glycoprotein ligand 1
-
-
?
3'-phosphoadenylyl sulfate + Ac-YLFSVHWPPLNK(COOSu)A-OH
adenosine 3',5'-bisphosphate + Ac-Y(O-sulfate)LFSVHWPPLNK(COOSu)A-OH
show the reaction diagram
-
an N-succinimidyl carbamate modified peptide substrate
-
-
?
3'-phosphoadenylyl sulfate + Ac-YLFSVHWPPLNKA-OH
adenosine 3',5'-bisphosphate + Ac-Y(O-sulfate)LFSVHWPPLNKA-OH
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylyl sulfate + benzyl-Glu-Tyr
adenosine 3',5'-bisphosphate + benzyl-Glu-Tyr-O-sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + C3aR tyrosine
adenosine 3',5'-bisphosphate + C3aR tyrosine O-sulfate
show the reaction diagram
-
C3a-anaphylatoxin chemotactic receptor,C3aR. Sulfation sequence motif is HNRCGY174KFGLSSSLDY184PDFY188 GDPLEQGFQDY317Y318NLGQF
-
-
?
3'-phosphoadenylyl sulfate + C5aR tyrosine
adenosine 3',5'-bisphosphate + C5aR tyrosine O-sulfate
show the reaction diagram
-
C5a-anaphylatoxin chemotactic receptor. Sulfation sequence motif is TTPDY11GHY14DDKDTLD
-
-
?
3'-phosphoadenylyl sulfate + CC receptor tyrosine
adenosine 3',5'-bisphosphate + CC receptor tyrosine O-sulfate
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylyl sulfate + CCR5 1-18 peptide
adenosine 3',5'-bisphosphate + sulfated CCR5 1-18peptide
show the reaction diagram
-
substrate is a synthetic human CCR5 peptide MDYQVSSPIYDINYYTSE-NH2. Sulfation pattern: Tyr3 is sulfated first, followed by Tyr14 or Tyr15, and finally Tyr10
-
-
?
3'-phosphoadenylyl sulfate + CCR5 2-18 peptide
adenosine 3',5'-bisphosphate + sulfated CCR5 2-18peptide
show the reaction diagram
-
substrate is a synthetic human CCR5 peptide DYQVSSPIYDINYYTSE-NH2. Sulfation pattern: Tyr14 and Tyr15 are sulfated first, followed by Tyr10, with Tyr3 sulfated last
-
-
?
3'-phosphoadenylyl sulfate + CCR8 1-17 M1A peptide
adenosine 3',5'-bisphosphate + sulfated CCR8 1-17 M1A peptide
show the reaction diagram
-
substrate is a synthetic modified mouse CCR8 peptide ADYTMEPNVTMTDYYPD-NH2. Sulfation pattern: Tyr3 is sulfated first, followed by Tyr14, with Tyr15 last
-
-
?
3'-phosphoadenylyl sulfate + CCR8 2-17 M1A peptide
adenosine 3',5'-bisphosphate + sulfated CCR8 2-17 M1A peptide
show the reaction diagram
-
substrate is a synthetic modified mouse CCR8 peptide DYTMEPNVTMTDYYPD-NH2. Sulfation pattern: Tyr14 is sulfated first, followed by Tyr3 and Tyr15
-
-
?
3'-phosphoadenylyl sulfate + CX3CR1 tyrosine
adenosine 3',5'-bisphosphate + CX3CR1 tyrosine O-sulfate
show the reaction diagram
3'-phosphoadenylyl sulfate + CXC-chemokine receptor 4
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
3'-phosphoadenylyl sulfate + CXCR4 1-38
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
CC-chemokine receptor 4 peptide, amino acids 1-38
the enzyme has a strong site preference for sulfation of Tyr-21 over Tyr-7 and Tyr-12, sulfation of Tyr-21 is required for high-affinity interaction with stromal cell-derived factor-1 (SDF-1alpha)
-
?
3'-phosphoadenylyl sulfate + CXCR4 peptide tyrosine
adenosine 3',5'-bisphosphate + CXCR4 peptide tyrosine O-sulfate
show the reaction diagram
-
a cytokine receptor peptide fragment
-
-
?
3'-phosphoadenylyl sulfate + EDFEDYEFDG
adenosine 3',5'-bisphosphate + EDFEDY(sulfated)EFDG
show the reaction diagram
GST-tagged CC4-tide, peptide 5-FAM-EDFEDYEFDG-CONH2, from human complement C4 protein
-
-
?
3'-phosphoadenylyl sulfate + EDYDTTTEFDsYGD
adenosine 3',5'-bisphosphate + EDsYDTTTEFDsYGD
show the reaction diagram
G protein-coupled receptor, human chemokine receptor 1, amino acids 8-20
-
-
?
3'-phosphoadenylyl sulfate + EDYDTTTEFDYGD
adenosine 3',5'-bisphosphate + EDYDTTTEFDsYGD
show the reaction diagram
G protein-coupled receptor human chemokine receptor 1, amino acids 8-20
-
-
?
3'-phosphoadenylyl sulfate + EEPEYGE
adenosine 3',5'-bisphosphate + EEPEY(O-sulfate)GE
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylyl sulfate + ENYSYDLDYYS
adenosine 3',5'-bisphosphate + ENsYSsYDLDsYsYS
show the reaction diagram
G protein-coupled receptor human gpr1, amino acids 13-23, sulfation order: first Tyr21, second Tyr22, third Tyr15 or 17, fourth Tyr 15 or 17
-
-
?
3'-phosphoadenylyl sulfate + ERHTRSYDYMEGGD
adenosine 3',5'-bisphosphate + ERHTRSYDY(sulfated)MEGGD
show the reaction diagram
FGF7-tide, peptide 5-FAM-ERHTRSYDYMEGGD-CONH2, from fibroblast growth factor 7
-
-
?
3'-phosphoadenylyl sulfate + FSHR tyrosine
adenosine 3',5'-bisphosphate + FSHR tyrosine O-sulfate
show the reaction diagram
-
follicle-stimulating hormone receptor, FSHR. Sulfation sequence motif is F-D/E-Y335
-
-
?
3'-phosphoadenylyl sulfate + human anionic trypsinogen tyrosine
adenosine 3',5'-bisphosphate + trypsinogen tyrosine O-sulfate
show the reaction diagram
i.e. serine protease 2, sulfation of Tyr154 facilitated by a unique sequence context which is characteristically found in primate trypsinogens
-
-
?
3'-phosphoadenylyl sulfate + LHR/CGR tyrosine
adenosine 3',5'-bisphosphate + LHR/CGR tyrosine O-sulfate
show the reaction diagram
-
luteinising hormone receptor, LHR/chorionic gonadotropin receptor, CGR. Sulfation sequence motif is Y385-D/E-Y
-
-
?
3'-phosphoadenylyl sulfate + P-selectin glycoprotein ligand-1
?
show the reaction diagram
recombinantly expressed substrate PSGL-1, glycoprotein found on the plasma membrane of neutrophils or monocytes. TPST activity on GST-tagged PSGL-1 is not affected by the GST fusion tag
-
-
?
3'-phosphoadenylyl sulfate + P-selectin glycoprotein ligand-1 tyrosine
adenosine 3',5'-bisphosphate + P-selectin glycoprotein ligand-1 tyrosine O-sulfate
show the reaction diagram
3'-phosphoadenylyl sulfate + peptide C4P5Y3
?
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + peptide EAY
adenosine 3',5'-bisphosphate + peptide EAY(O-sulfate)
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylyl sulfate + peptide Y+1 tyrosine
adenosine 3',5'-bisphosphate + peptide Y+1 tyrosine-O-sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + poly-Glu6Ala3Tyr1 peptide
adenosine 3',5'-bisphosphate + poly-Glu6Ala3Tyrsulfate peptide
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylyl sulfate + protein tyrosine
adenosine 3',5'-bisphosphate + protein tyrosine O-sulfate
show the reaction diagram
3'-phosphoadenylyl sulfate + protein tyrosine
adenosine 3',5'-bisphosphate + protein tyrosine-O-sulfate
show the reaction diagram
3'-phosphoadenylyl sulfate + PSGL-1
adenosine 3',5'-bisphosphate + PSGL-1 sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + PSGL-1 1-15 peptide
adenosine 3',5'-bisphosphate + sulfated PSGL-1 1-15 peptide
show the reaction diagram
QATEYEYLDYDFLPE-NH2
-
-
?
3'-phosphoadenylyl sulfate + PSGL-1 protein
adenosine 3',5'-bisphosphate + PSGL-1 protein tyrosine-O-sulfate
show the reaction diagram
-
i.e. ATEYEYLDYDFL
-
-
?
3'-phosphoadenylyl sulfate + QATEYEYLDYDFLPE
adenosine 3',5'-bisphosphate + QATEsYEsYLDsYDFLPE
show the reaction diagram
human PSGL-1, amino acids 42-56, sulfation order: first Tyr51, second Tyr46 or 48, third Tyr46 or 48
-
-
?
3'-phosphoadenylyl sulfate + QATEYEYLDYDFLPE-NH2
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
P-selectin glycoprotein ligand-1, amino acids 1-15
-
-
?
3'-phosphoadenylyl sulfate + S1P1R tyrosine
adenosine 3',5'-bisphosphate + S1P1R tyrosine O-sulfate
show the reaction diagram
-
type 1 Sphingosine 1-phosphate receptor, S1P1R. Sulfation sequence motif is D-Y19-V/G/-N-Y22-D
-
-
?
3'-phosphoadenylyl sulfate + statherin
adenosine 3',5'-bisphosphate + statherin O-sulfate
show the reaction diagram
3'-phosphoadenylyl sulfate + statherin
adenosine 3',5'-bisphosphate + statherin-O-sulfate
show the reaction diagram
-
a 43-residue polypeptide, which is tyrosine-rich and contains 7 tyrosine residues
-
-
?
3'-phosphoadenylyl sulfate + SYGDEYPDYLD
adenosine 3',5'-bisphosphate + SsYGDEsYPDsYLD
show the reaction diagram
G protein-coupled receptor human dez, amino acids 13-23, sulfation order: first Tyr21, second Tyr18, third Tyr14
-
-
?
3'-phosphoadenylyl sulfate + TEYEYLDYDFLPETE
adenosine 3',5'-bisphosphate + TEYEYLDY(sulfated)DFLPETE
show the reaction diagram
PSGL1-tide, peptide 5-FAM-TEYEYLDYDFLPETE-CONH2, from P-selectin glycoprotein ligand-1
-
-
?
3'-phosphoadenylyl sulfate + trypsinogen tyrosine
adenosine 3',5'-bisphosphate + trypsinogen tyrosine O-sulfate
show the reaction diagram
sulfation of Tyr154 with Asp as important determinant. Mutation D153N, a naturally occuring polymorphisms in African population, results in a complete loss of trypsinogen sulfation, while mutation of Gly151 and Pro155 of the trypsinogen has no effect on enzyme activity. Genotyping of different populations for the substrate polymorphism, overview
-
-
?
3'-phosphoadenylyl sulfate + TSHR tyrosine
adenosine 3',5'-bisphosphate + TSHR tyrosine O-sulfate
show the reaction diagram
-
thyroid-stimulating hormone receptor, TSHR. Sulfation sequence motif is Y385-D/E-Y
-
-
?
3'-phosphoadenylyl sulfate + TTFFDsYDYGA
adenosine 3',5'-bisphosphate + TTFFDsYDsYGA
show the reaction diagram
G protein-coupled receptor, human chemokine receptor 2, amino acids 21-30
-
-
?
3'-phosphoadenylyl sulfate + TTFFDYDsYGA
adenosine 3',5'-bisphosphate + TTFFDsYDsYGA
show the reaction diagram
G protein-coupled receptor, human chemokine receptor 2, amino acids 21-30
-
-
?
3'-phosphoadenylyl sulfate + TTFFDYDYGA
adenosine 3',5'-bisphosphate + TTFFDsYDYGA
show the reaction diagram
G protein-coupled receptor, human chemokine receptor 2, amino acids 21-30
-
-
?
3'-phosphoadenylyl sulfate + TTFFDYDYGA
adenosine 3',5'-bisphosphate + TTFFDYDsYGA
show the reaction diagram
G protein-coupled receptor, human chemokine receptor 2, amino acids 21-30
-
-
?
3'-phosphoadenylyl sulfate + TTVTDYYYPDIFSS
adenosine 3',5'-bisphosphate + TTVTDY(sulfated)YYPDIFSS
show the reaction diagram
CCR8-tide, peptide 5-FAM-TTVTDYYYPDIFSS-CONH2, from C-C motif chemokine receptor 8
-
-
?
3'-phosphoadenylyl sulfate + Tyr-Tyr-Tyr
adenosine 3',5'-bisphosphate + Tyr-Tyr-Tyr-O-sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + vitronectin peptide
adenosine 3',5'-bisphosphate + vitronectin-O-sulfate
show the reaction diagram
amino acids 75-91, Y(SO3H)TVY(SO3H)DDGEEKNDATVHE
-
-
?
3'-phosphoadenylyl sulfate + VTDsYsYYPDI
adenosine 3',5'-bisphosphate + VTDsYsYsYPDI
show the reaction diagram
Tyr16-sulfated G protein-coupled receptor CCR8, amino acids 12-20
-
-
?
3'-phosphoadenylyl sulfate + VTDsYYsYPDI
adenosine 3',5'-bisphosphate + VTDsYsYsYPDI
show the reaction diagram
CC-chemokine receptor 8 nonapeptide, sY15CCR8
-
-
?
3'-phosphoadenylyl sulfate + VTDsYYYPDG
adenosine 3',5'-bisphosphate + VTDsYYsYPDI
show the reaction diagram
CC-chemokine receptor 8 nonapeptide, sY15sY17CCR8
-
-
?
3'-phosphoadenylyl sulfate + VTDsYYYPDI
adenosine 3',5'-bisphosphate + VTDsYYsYPDI
show the reaction diagram
3'-phosphoadenylyl sulfate + VTDYsYYPDI
adenosine 3',5'-bisphosphate + VTDsYsYYPDI
show the reaction diagram
Tyr16-sulfated G protein-coupled receptor CCR8, amino acids 12-20
-
-
?
3'-phosphoadenylyl sulfate + VTDYYsYPDI
adenosine 3',5'-bisphosphate + VTDsYYsYPDI
show the reaction diagram
both isoenzymes sequentially sulfate the CCR8 peptide such that Tyr15 is sulfated first followed by Tyr17 sulfation
-
-
?
3'-phosphoadenylyl sulfate + VTDYYYPDI
adenosine 3',5'-bisphosphate + VTDsYYYPDI
show the reaction diagram
3'-phosphoadenylyl sulfate + VTDYYYPDI
adenosine 3',5'-bisphosphate + VTDYYsYPDI
show the reaction diagram
a peptide modeled on the N-terminal extracellular domain of human CCR8, amino acids 12-20
-
-
?
3'-phosphoadenylyl sulfate + [PSGL-1 peptide]-L-tyrosine
adenosine 3',5'-bisphosphate + [PSGL-1 peptide]-L-tyrosine-O-sulfate
show the reaction diagram
-
-
-
?
3'-phosphoadenylyl sulfate + [Y+3 peptide]-L-tyrosine
adenosine 3',5'-bisphosphate + [Y+3 peptide]-L-tyrosine-O-sulfate
show the reaction diagram
i.e. biotin-RDRRQATEYEYLDYDFLPETEPPP
-
-
?
3'-phosphoadenylylsulfate + acidic amino acid polymer EAY
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
-
i.e. poly-EAY or Glu6,Ala3,Tyr1, model substrate
-
-
?
3'-phosphoadenylylsulfate + acidic polypeptide tyrosine
adenosine 3',5'-bisphosphate + acidic polypeptide tyrosine-O-sulfate
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylylsulfate + C4 alpha chain
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
-
more efficiently sulphated by TPST1 than TPST2
-
-
?
3'-phosphoadenylylsulfate + DYQVSSPIYDINYYTSE
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
-
amino acids 2-18 derived from peptide CC-chemokine receptor 5, final product has four sulfotyrosine residues, sulfation occurs in the following order: Tyr13, Tyr14, Tyr9, Tyr2
-
-
?
3'-phosphoadenylylsulfate + heparin cofactor II
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
-
more efficiently sulphated by TPST1 than TPST2
-
-
?
3'-phosphoadenylylsulfate + protein tyrosine
adenosine 3',5'-bisphosphate + acidic polypeptide tyrosine-O-sulfate
show the reaction diagram
-
post-translational modification of biologically active peptides and proteins
-
-
?
3'-phosphoadenylylsulfate + QATEYEYLDYDFLPE
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
-
derived from N-terminal residues of the mature leukocyte adhesion molecule P-selectin glycoprotein ligand 1
-
-
?
additional information
?
-
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
3'-phosphoadenylyl sulfate + CXC-chemokine receptor 4
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
CXCR4 signaling is indispensable for embryonic development
-
-
?
3'-phosphoadenylyl sulfate + protein tyrosine
adenosine 3',5'-bisphosphate + protein tyrosine-O-sulfate
show the reaction diagram
3'-phosphoadenylyl sulfate + C3aR tyrosine
adenosine 3',5'-bisphosphate + C3aR tyrosine O-sulfate
show the reaction diagram
-
C3a-anaphylatoxin chemotactic receptor,C3aR. Sulfation sequence motif is HNRCGY174KFGLSSSLDY184PDFY188 GDPLEQGFQDY317Y318NLGQF
-
-
?
3'-phosphoadenylyl sulfate + C5aR tyrosine
adenosine 3',5'-bisphosphate + C5aR tyrosine O-sulfate
show the reaction diagram
-
C5a-anaphylatoxin chemotactic receptor. Sulfation sequence motif is TTPDY11GHY14DDKDTLD
-
-
?
3'-phosphoadenylyl sulfate + CC receptor tyrosine
adenosine 3',5'-bisphosphate + CC receptor tyrosine O-sulfate
show the reaction diagram
-
-
-
-
?
3'-phosphoadenylyl sulfate + CX3CR1 tyrosine
adenosine 3',5'-bisphosphate + CX3CR1 tyrosine O-sulfate
show the reaction diagram
-
a cytokine receptor for CXCL10/IP-10 and CXCL11/I-TAC, contains two potential tyrosine sulfation sites within the sequence ENFSSSY27DY29GENESDS
-
-
?
3'-phosphoadenylyl sulfate + CXC-chemokine receptor 4
adenosine 3',5'-bisphosphate + ?
show the reaction diagram
CXCR4 signaling is indispensable for embryonic development
-
-
?
3'-phosphoadenylyl sulfate + FSHR tyrosine
adenosine 3',5'-bisphosphate + FSHR tyrosine O-sulfate
show the reaction diagram
-
follicle-stimulating hormone receptor, FSHR. Sulfation sequence motif is F-D/E-Y335
-
-
?
3'-phosphoadenylyl sulfate + LHR/CGR tyrosine
adenosine 3',5'-bisphosphate + LHR/CGR tyrosine O-sulfate
show the reaction diagram
-
luteinising hormone receptor, LHR/chorionic gonadotropin receptor, CGR. Sulfation sequence motif is Y385-D/E-Y
-
-
?
3'-phosphoadenylyl sulfate + P-selectin glycoprotein ligand-1 tyrosine
adenosine 3',5'-bisphosphate + P-selectin glycoprotein ligand-1 tyrosine O-sulfate
show the reaction diagram
-
sulfoTyr plays a functional role is P-selectin glycoprotein ligand-1, which is involved in leukocyte-mediated inflammation
-
-
?
3'-phosphoadenylyl sulfate + protein tyrosine
adenosine 3',5'-bisphosphate + protein tyrosine O-sulfate
show the reaction diagram
3'-phosphoadenylyl sulfate + protein tyrosine
adenosine 3',5'-bisphosphate + protein tyrosine-O-sulfate
show the reaction diagram
3'-phosphoadenylyl sulfate + PSGL-1 protein
adenosine 3',5'-bisphosphate + PSGL-1 protein tyrosine-O-sulfate
show the reaction diagram
-
i.e. ATEYEYLDYDFL
-
-
?
3'-phosphoadenylyl sulfate + S1P1R tyrosine
adenosine 3',5'-bisphosphate + S1P1R tyrosine O-sulfate
show the reaction diagram
-
type 1 Sphingosine 1-phosphate receptor, S1P1R. Sulfation sequence motif is D-Y19-V/G/-N-Y22-D
-
-
?
3'-phosphoadenylyl sulfate + statherin
adenosine 3',5'-bisphosphate + statherin O-sulfate
show the reaction diagram
-
TPST is responsible for the sulfation of a variety of secretory and membrane proteins, e.g. of the salivary secretory protein, statherin
-
-
?
3'-phosphoadenylyl sulfate + trypsinogen tyrosine
adenosine 3',5'-bisphosphate + trypsinogen tyrosine O-sulfate
show the reaction diagram
sulfation of Tyr154 with Asp as important determinant. Mutation D153N, a naturally occuring polymorphisms in African population, results in a complete loss of trypsinogen sulfation, while mutation of Gly151 and Pro155 of the trypsinogen has no effect on enzyme activity. Genotyping of different populations for the substrate polymorphism, overview
-
-
?
3'-phosphoadenylyl sulfate + TSHR tyrosine
adenosine 3',5'-bisphosphate + TSHR tyrosine O-sulfate
show the reaction diagram
-
thyroid-stimulating hormone receptor, TSHR. Sulfation sequence motif is Y385-D/E-Y
-
-
?
3'-phosphoadenylyl sulfate + VTDsYYYPDI
adenosine 3',5'-bisphosphate + VTDsYYsYPDI
show the reaction diagram
-
-
-
-
ir
3'-phosphoadenylyl sulfate + VTDYYYPDI
adenosine 3',5'-bisphosphate + VTDsYYYPDI
show the reaction diagram
-
-
-
-
ir
3'-phosphoadenylylsulfate + protein tyrosine
adenosine 3',5'-bisphosphate + acidic polypeptide tyrosine-O-sulfate
show the reaction diagram
-
post-translational modification of biologically active peptides and proteins
-
-
?
additional information
?
-
-
sulfation patterns, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mn2+
activates isozymes TPST-1
Co2+
-
20 mM, stimulates
MnCl2
-
required, maximal activity at 20 mM
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3'-phosphoadenosine 5'-phosphate
-
adenosine 3',5'-bisphosphate
product inhibition
aurintricarboxylic acid
complete inhibition at 0.02 mM
dabrafenib
complete inhibition of TPST1 at 0.4 mM
dephospho-CoA
inhibits slightly at 0.1 mM, the inhibition is increased by addition of PAPS
fluphenazine
-
guanidinyl-naltrindole di-trifluoroacetate
77% inhibition at 0.02 mM
-
PSGL-1 peptide
-
-
RAF265
a phase I imidazo-benzimidazole RAF inhibitor, complete inhibition of TPST1 at 0.4 mM
-
rottlerin
sorafenib
complete inhibition of TPST1 at 0.4 mM
suramin
possesses inhibitory properties consistent with a competitive inhibitor of substrate binding, molecular docking reveals a good fit of suramin into the TPST2 substrate-binding pocket, inhibition kinetic mechanism, overview. Complete inhibition at 0.02 mM
vemurafenib
complete inhibition of TPST1 at 0.4 mM, vemurafenib potentially induces partial TPST-1 activation at lower concentrations, inhibiting the activity at higher concentrations
-
ZM336372
complete inhibition of TPST1 at 0.4 mM
3'-phosphoadenosine 5'-phosphate
-
adenosine 3',5'-bisphosphate
aurintricarboxylic acid
95% inhibition at 0.02 mM
Ca2+
-
inhibits both isozymes
EDTA
-
-
fluphenazine
-
guanidinyl-naltrindole di-trifluoroacetate
74% inhibition at 0.02 mM
-
Poly-EAY
-
substrate inhibition, above 0.002 mM
PSGL-1 peptide
-
-
suramin
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
vemurafenib
complete inhibition of TPST1 at 0.4 mM, vemurafenib potentially induces partial TPST-1 activation at lower concentrations, inhibiting the activity at higher concentrations
-
Lubrol Px
Mg2+
-
strongly stimulates isozyme TPST-2, but not TPST-1
Mn2+
-
strong activation of both isozymes
Triton X-100
-
activation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0051 - 0.54
3'-phosphoadenylyl sulfate
1.297
benzyl-Glu-Tyr
pH 6.0, 30°C, isozyme TPST-1
0.00767
C4P5Y5 peptide
recombinant enzyme TPST1, pH 6.0, 30°C
-
0.652
gastrin peptide
recombinant enzyme TPST1, pH 6.0, 30°C
-
0.002 - 0.0044
peptide Y+1 tyrosine
-
0.0097
PSGL-1
pH 6.0, 30°C, isozyme TPST-1
-
0.0175
Tyr-Tyr-Tyr
pH 6.0, 30°C, isozyme TPST-1
17 - 21
VTDsYYsYPDI
75 - 99
VTDYYYPDI
0.0019
[Y+3 peptide]-L-tyrosine
isoform TPST1, at pH 7.5 and 25°C
-
0.0048 - 0.59
3'-phosphoadenylyl sulfate
1.223
benzyl-Glu-Tyr
pH 6.0, 30°C, isozyme TPST-2
0.0015 - 0.0016
peptide EAY
-
-
-
0.002 - 0.0044
peptide Y+1 tyrosine
-
0.0269
PSGL-1
pH 6.0, 30°C, isozyme TPST-2
-
0.04
statherin
-
0.022
Tyr-Tyr-Tyr
pH 6.0, 30°C, isozyme TPST-2
2 - 17
VTDsYYsYPDI
0.0031
VTDsYYYPDI
-
in 20 mM MOPS, at pH 7.5, 100 mM NaCl, at 30°C
0.0193 - 120
VTDYYYPDI
0.0018
[Y+3 peptide]-L-tyrosine
isoform TPST2, at pH 7.5 and 25°C
-
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00082
C4P5Y5 peptide
recombinant enzyme TPST1, pH 6.0, 30°C
-
0.00011
gastrin peptide
recombinant enzyme TPST1, pH 6.0, 30°C
-
0.054
[Y+3 peptide]-L-tyrosine
isoform TPST1, at pH 7.5 and 25°C
-
0.065
[Y+3 peptide]-L-tyrosine
isoform TPST2, at pH 7.5 and 25°C
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.107
C4P5Y5 peptide
recombinant enzyme TPST1, pH 6.0, 30°C
-
0.00017
gastrin peptide
recombinant enzyme TPST1, pH 6.0, 30°C
-
29
[Y+3 peptide]-L-tyrosine
isoform TPST1, at pH 7.5 and 25°C
-
37
[Y+3 peptide]-L-tyrosine
isoform TPST2, at pH 7.5 and 25°C
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00016 - 0.00074
adenosine 3',5'-bisphosphate
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0099
3'-phosphoadenosine 5'-phosphate
Homo sapiens
isoform TPST1, at pH 7.5 and 25°C
0.0015
adenosine 3',5'-bisphosphate
Homo sapiens
pH 7.4, 20°C, recombinant His6-tagged enzyme
0.3786
ATP
Homo sapiens
pH 7.4, 20°C, recombinant His6-tagged enzyme
0.00045
aurintricarboxylic acid
Homo sapiens
pH 6.5, 22°C, recombinant TPST1
0.0873
CoA
Homo sapiens
pH 7.4, 20°C, recombinant His6-tagged enzyme
0.1665
dephospho-CoA
Homo sapiens
pH 7.4, 20°C, recombinant His6-tagged enzyme
0.0024
guanidinyl-naltrindole di-trifluoroacetate
Homo sapiens
pH 6.5, 22°C, recombinant TPST1
-
0.0005
PSGL-1 peptide
Homo sapiens
isoform TPST1, at pH 7.5 and 25°C
-
0.0065
RAF265
Homo sapiens
pH 7.4, 20°C, recombinant His6-tagged enzyme
-
0.0014
suramin
Homo sapiens
pH 6.5, 22°C, recombinant TPST1
0.011
3'-phosphoadenosine 5'-phosphate
Homo sapiens
isoform TPST2, at pH 7.5 and 25°C
0.00046
aurintricarboxylic acid
Homo sapiens
pH 6.5, 22°C, recombinant TPST1
0.0016
guanidinyl-naltrindole di-trifluoroacetate
Homo sapiens
pH 6.5, 22°C, recombinant TPST1
-
0.0007
PSGL-1 peptide
Homo sapiens
isoform TPST2, at pH 7.5 and 25°C
-
0.0014
suramin
Homo sapiens
pH 6.5, 22°C, recombinant TPST1
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0000031
recombinant TPST-1 in HEK-293T cell extract
0.0000032
recombinant TPST-2 in HEK-293T cell extract
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
peripheral leukocyte
Manually annotated by BRENDA team
-
TPST-2 shows higher expression as TPST-1
Manually annotated by BRENDA team
-
primary culture of umbilical vein endothelial cells, 2 isoforms: TPST1 and TPST2, shear stress causes a shift in protein expression from TPST1 to TPST2
Manually annotated by BRENDA team
-
breast cancer cell line, isozyme TPST-2
Manually annotated by BRENDA team
-
isozymes TPST-1 and TPST-2
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
TPST-1 displays type II transmembrane topology with a short N-terminal cytoplasmic domain, a single 17-residue transmembrane domain, and a luminal catalytic domain
Manually annotated by BRENDA team
TPST-2 displays type II transmembrane topology with a short N-terminal cytoplasmic domain, a single 17-residue transmembrane domain, and a luminal catalytic domain
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
mechanistic inhibition of cellular tyrosine sulfation might be relevant to some of the phenotypes observed in cells exposed to anionic TPST ligands and RAF protein kinase inhibitors. Multiple RAF kinase inhibitors target TPST catalytic activity in vitro
metabolism
biological sulfation (also called sulfonation) is a widespread covalent chemical modification of biomolecules by the addition of a sulfonyl group (SO3-). Inorganic sulfate is made available for incorporation into biomolecules in the form of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) through a process in which ATP is first sulfated by the ATP sulfurylase enzyme to generate adenosine 5'-phosphosulfate, which is then phosphorylated on the 3' position of the ribose ring to generate PAPS. Sulfation is carried out by a class of enzymes called sulfotransferases
physiological function
malfunction
mechanistic inhibition of cellular tyrosine sulfation might be relevant to some of the phenotypes observed in cells exposed to anionic TPST ligands and RAF protein kinase inhibitors. Multiple RAF kinase inhibitors target TPST catalytic activity in vitro
metabolism
-
the two independent TPSTs catalyze the tyrosine-O-sulfation, a post-translational modification
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
TPST1_HUMAN
370
0
42188
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
42190
calculated from nucleotide sequence
45000
x * 45000, SDS-PAGE
54000
SDS-PAGE
45000
x * 45000, SDS-PAGE
54000
-
x * 54000, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 45000, SDS-PAGE
homodimer
heterodimer
-
isoforms TPST1/TPST2 also organize as heterodimer with sialyltransferases
homodimer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
glycoprotein
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
human TPST1 in complex with adenosine 3'-5' diphosphate (PAP) and two different substrate peptides (PDB codes 5WRI and 5WRJ)
purified TPST1 complexed with two substrate peptides, C4 complement-deived C4P5Y5 or a gastrin peptide, and PAP. PST1-PAP-C4P5Y5 is crystallized by sitting drop vapor diffusion method, mixing of 2.5 mg/ml protein, 2 mM PAP, and 1 mM C4P5Y5 peptide in 50 mM Tris-HCl, pH 7.0, and 200 mM NaCl with reservoir solution consisting of 0.2 M trimethylamine N-oxide dihydrate, 0.1 M Tris-HCl, pH 8.5, and 20% w/v PEG monomethyl ether 2000, nine months, at 20°C. TPST1-PAP-gastrin peptide is crystallized by sitting drop vapor diffusion method, mixing of 5.0 mg/ml protein, 2 mM PAP, and 3 mM gastrin peptide in 50 mM Tris-HCl, pH 7.0, and 200 mM NaCl with reservoir solution consisting of 0.2 M potassium sodium tartrate trihydrate and 19.5% w/v PEG 3350, two months, at 20°C. X-ray diffraction structure determination and analysis at 1.6 A and 2.3 A resolution, respectively. The asymmetric unit of human TPST1-PAP-C4P5Y5 contains two human TPST1 molecules, which assemble to form a dimer. In contrast, the asymmetric unit of TPST1-PAP-gastrin peptide contains four human TPST1 molecules, which assemble to form two dimers
determination of crystal and three dimensional structures of the isozymes
-
in complex with substrate peptide C4P5Y3
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E99A
active site mutant
K158A
active site mutant
N262A
-
site-directed mutagenesis, the N-glycosylation site mutant is less N-glycosylated and has a lower molecular weight compared to the wild-type enzyme
N60A
-
site-directed mutagenesis, the N-glycosylation site mutant is less N-glycosylated and has a lower molecular weight compared to the wild-type enzyme
R101A
substrate binding mutant which exhibits nearly complete loss of enzyme activity
R105A
substrate binding mutant
R122A
substrate binding mutant
R78A
active site mutant
S285A
active site mutant
T198A
substrate binding mutant
W113A
the mutant is not able to dimerize
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
40.3
Tm of purified recombinant His6-tagged TPST1
39.8
Tm of purified recombinant His6-tagged TPST2
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the purified recombinant enzyme is thermally stabilized by PAPS, kinetics, overview
TPST isozymes are stabilised by cofactors such as CoA
the purified recombinant enzyme is thermally stabilized by PAPS, kinetics, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
anti-protein C immunoaffinity chromatography
Ni-NTA column chromatography, and Superdex 200 gel filtration
preparation of TPST from Golgi-enriched membrane fractions, recombinant His-tagged GST- or NusA-fused enzyme from Escherichia coli strain BL21(DE3) to homogeneity by nickel affinity chromatography, low solubility or contamination with tag material
recombinant engineered isozyme TPST-1 from HEK293-T cells by solubilization with 1% v/v Triton X-100, anti-protein C affinity chromatography, and ultrafiltration. Recombinant His6-tagged TPST-1 from Escherichia coli strain BL21(DE3)inclusion bodies after solubilization and refolding by glutathione affinity chromatography, ultrafiltration, cleavage of the tag by Precission protease, and gel filtration
recombinant enzyme
recombinant His6-tagged TPST1 (residues Lys43-Leu360) lacking the transmembrane domain, solubilized and refolded from inclusion bodies after expression in Escherichia coli strain BL21(DE3)pLysS by nickel affinity chromatography and gel filtration
recombinant N-terminally His6-tagged TPST1 (Lys43-Glu370) from Escherichia coli strain Origami (DE3) by nickel affinity chromatography, ultrafiltration and gel filtration, the tag is cleaved off through thrombin, thrombin is removed by benzamidine affinity chromatography, followed by desalting gel filtration
recombinant TPST1 from Spodoptera frugiperda cells
2 recombinant isoforms: TPST1 and TPST2
-
anti-protein C immunoaffinity chromatography
HPC4 affinity column chromatography, and gel filtration
-
Ni-NTA column chromatography, and Superdex 200 gel filtration
partial
-
preparation of TPST from Golgi-enriched membrane fractions, recombinant His-tagged GST- or NusA-fused enzyme from Escherichia coli strain BL21(DE3) to homogeneity by nickel affinity chromatography, low solubility or contamination with tag material
recombinant engineered isozyme TPST-1 from HEK293-T cells by solubilization with 1% v/v Triton X-100, anti-protein C affinity chromatography, and ultrafiltration
recombinant His6-tagged TPST2 (residues Gly43-Leu359) lacking the transmembrane domain, solubilized and refolded from inclusion bodies after expression in Escherichia coli strain BL21(DE3)pLysS by nickel affinity chromatography and gel filtration
recombinant TPST1 from Spodoptera frugiperda cells
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in CHO cells
expressed in Sf9 insect cells
expression in HEK-293T cells
expression of isozyme TPST-1 in HEK-293T cells, quantitative real-time PCR expression analysis
gene TPST1, cloning of isozyme TPST-1 without the cytoplasmic N-terminus and the transmembrane domain, which are not required for enzymatic activity, und an N-terminal transferring signal peptide followed by a protein C epitope are N-terminally fused to the catalytic domain (residues 25 to 370 of full-length isozyme), transient recombinant expression in HEK293-T cells. Recombinant expression of His6-tagged isozyme TPST-1 in Escherichia coli strain BL21(DE3) in inclusion bodies
gene TPST1, recombinant expression in Spodoptera frugiperda cells using the baculovirus transfection method
gene TPST1, recombinant expression of His-tagged enzyme fused to GST or NusA in Escherichia coli strain BL21(DE3), method optimization, overview
gene TPST1, recombinant expression of N-terminally His6-tagged TPST1 (residues Lys43-Leu360) lacking the transmembrane domains in Escherichia coli strain BL21(DE3)pLysS in inclusion bodies
recombinant expression of N-terminally His6-tagged TPST1 (Lys43-Glu370) in Escherichia coli strain Origami (DE3) carrying the pGro7 plasmid encoding chaperonin proteins
2 isoforms: TPST1 and TPST2
-
expressed in CHO-K1 cells
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Sf9 insect cells
expression in HEK-293T cells
expression of isozyme TPST-2 in HEK-293T cells, quantitative real-time PCR expression analysis
expression of TPSt-1 in HeLa cells and COS-7 cells as GFP-tagged protein in the Golgi compartment
-
gene TPST1, recombinant expression in Spodoptera frugiperda cells using the baculovirus transfection method
gene TPST2, cloning of isozyme TPST-2 without the cytoplasmic N-terminus and the transmembrane domain, which are not required for enzymatic activity, und an N-terminal transferring signal peptide followed by a protein C epitope are N-terminally fused to the catalytic domain (residues 25 to 377 of full-length isozyme), transient recombinant expression in HEK293-T cells
gene TPST2, recombinant expression of His-tagged enzyme fused to GST or NusA in Escherichia coli strain BL21(DE3), method optimization, overview
gene TPST2, recombinant expression of N-terminally His6-tagged TPST2 (residues Gly43-Leu359) lacking the transmembrane domains in Escherichia coli strain BL21(DE3)pLysS in inclusion bodies
isozymes TPST-1 and TPST-2, DNA and amino acid sequence determinationand analysis, sequence comparison
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
isoform TPST-1 is down-regulated in a dose-dependent manner when increasing shear stress stimulus is applied to cells
isoform TPST-2 is up-regulated in a dose-dependent manner when increasing shear stress stimulus is applied to cells
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
functional refolding of recombinant GST-tagged TPST-1 expressed in Escherichia coli strain BL21(DE3) in inclusion bodies using 6 M guanidine hydrochloride (GndHCl), glutathione, and n-dodecyl-beta-D-maltoside
recombinant His6-tagged TPST1 (residues Lys43-Leu360) lacking the transmembrane domains from Escherichia coli strain BL21(DE3)pLysS inclusion bodies by ultrafiltration, dilution in 100 mM Na-acetate, pH 4.5, 6 M guanidine hydrochloride, and 10 mM DTT, concentrated TPST (about 150 mg) is slowly added to refolding buffer containing 50 mM Tris-HCl, pH 8.5, 500 mM guanidine hydrochloride, 10 mM NaCl, 0.4 mM KCl, 0.1 mM EDTA, 0.14 mM n-dodecyl beta-D-maltoside, 5 mM reduced glutathione, and 2.5 mM oxidised glutathione. The refolding mixture is then incubated for 20 h at 4°C without mixing and precipitated protein is subsequently removed by centrifugation
recombinant His6-tagged TPST2 (residues Gly43-Leu359) lacking the transmembrane domains from Escherichia coli strain BL21(DE3)pLysS inclusion bodies by ultrafiltration, dilution in 100 mM Na-acetate, pH 4.5, 6 M guanidine hydrochloride, and 10 mM DTT, concentrated TPST (about 150 mg) is slowly added to refolding buffer containing 50 mM Tris-HCl, pH 8.5, 500 mM guanidine hydrochloride, 10 mM NaCl, 0.4 mM KCl, 0.1 mM EDTA, 0.14 mM n-dodecyl beta-D-maltoside, 5 mM reduced glutathione, and 2.5 mM oxidised glutathione. The refolding mixture is then incubated for 20 h at 4°C without mixing and precipitated protein is subsequently removed by centrifugation
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
isoform TPST1 expression is associated with the tumornodemetastasis stage and lymph node metastasis in patients with lung cancer
synthesis
usage of tyrosylprotein sulfotransferases for in vitro one-pot enzymatic synthesis of sulfated proteins/peptides
molecular biology
-
conjugation of proteins with N-carbamoyl-succinate-modified peptides is an appropriate tool in research, for instance, in the development of vaccines and drugs or for studying biological mechanisms
synthesis
usage of tyrosylprotein sulfotransferases for in vitro one-pot enzymatic synthesis of sulfated proteins/peptides
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rens-Domiano, S.; Roth, J.A.
Characterization of tyrosylprotein sulfotransferase from rat liver and other tissues
J. Biol. Chem.
264
899-905
1989
Homo sapiens, Mesocricetus auratus, Mus musculus, Oryctolagus cuniculus, Rattus norvegicus
Manually annotated by BRENDA team
Lin, W.H.; Roth, J.A.
Characterization of a tyrosylprotein sulfotransferase in human liver
Biochem. Pharmacol.
40
629-635
1990
Homo sapiens
Manually annotated by BRENDA team
Goettsch, S.; Goettsch, W.; Morawietz, H.; Bayer, P.
Shear stress mediates tyrosylprotein sulfotransferase isoform shift in human endothelial cells
Biochem. Biophys. Res. Commun.
294
541-546
2002
Homo sapiens
Manually annotated by BRENDA team
Moore, K.L.
The biology and enzymology of protein tyrosine O-sulfation
J. Biol. Chem.
278
24243-24246
2003
Homo sapiens, Mammalia, no activity in yeast, no activity in prokaryotes, Drosophila melanogaster (Q9VYB7)
Manually annotated by BRENDA team
Ouyang, Y.; Lane, W.S.; Moore, K.L.
Tyrosylprotein sulfotransferase: purification and molecular cloning of an enzyme that catalyzes tyrosine O-sulfation, a common posttranslational modification of eukaryotic proteins
Proc. Natl. Acad. Sci. USA
95
2896-2901
1998
Homo sapiens (O60507), Homo sapiens, Mus musculus (O70281), Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Seibert, C.; Cadene, M.; Sanfiz, A.; Chait, B.T.; Sakmar, T.P.
Tyrosine sulfation of CCR5 N-terminal peptide by tyrosylprotein sulfotransferases 1 and 2 follows a discrete pattern and temporal sequence
Proc. Natl. Acad. Sci. USA
99
11031-11036
2002
Homo sapiens
Manually annotated by BRENDA team
Kasinathan, C.; Ramaprasad, P.; Sundaram, P.
Identification and characterization of tyrosylprotein sulfotransferase from human saliva
Int. J. Biol. Sci.
1
141-145
2005
Homo sapiens
Manually annotated by BRENDA team
Mishiro, E.; Sakakibara, Y.; Liu, M.; Suiko, M.
Differential enzymatic characteristics and tissue-specific expression of human TPST-1 and TPST-2
J. Biochem.
140
731-737
2006
Homo sapiens (O60507), Homo sapiens (O60704), Homo sapiens
Manually annotated by BRENDA team
Goettsch, S.; Badea, R.A.; Mueller, J.W.; Wotzlaw, C.; Schoelermann, B.; Schulz, L.; Rabiller, M.; Bayer, P.; Hartmann-Fatu, C.
Human TPST1 transmembrane domain triggers enzyme dimerisation and localisation to the Golgi compartment
J. Mol. Biol.
361
436-449
2006
Homo sapiens
Manually annotated by BRENDA team
Kasinathan, C.; Jean, S.; Manowitz, P.
Tyrosine sulfation of arylsulfatase A and its peptide
Protein Pept. Lett.
13
357-361
2006
Homo sapiens
Manually annotated by BRENDA team
Seibert, C.; Veldkamp, C.T.; Peterson, F.C.; Chait, B.T.; Volkman, B.F.; Sakmar, T.P.
Sequential tyrosine sulfation of CXCR4 by tyrosylprotein sulfotransferases
Biochemistry
47
11251-11262
2008
Homo sapiens (O60507), Homo sapiens (O60704), Homo sapiens
Manually annotated by BRENDA team
Nishimura, M.; Naito, S.
Tissue-specific mRNA expression profiles of human carbohydrate sulfotransferase and tyrosylprotein sulfotransferase
Biol. Pharm. Bull.
30
821-825
2007
Homo sapiens, Homo sapiens (O60507)
Manually annotated by BRENDA team
Kasinathan, C.; Gandhi, N.; Ramaprasad, P.; Sundaram, P.; Ramasubbu, N.
Tyrosine sulfation of statherin
Int. J. Biol. Sci.
3
237-241
2007
Homo sapiens
Manually annotated by BRENDA team
Danan, L.M.; Yu, Z.; Hoffhines, A.J.; Moore, K.L.; Leary, J.A.
Mass spectrometric kinetic analysis of human tyrosylprotein sulfotransferase-1 and -2
J. Am. Soc. Mass Spectrom.
19
1459-1466
2008
Homo sapiens (O60507), Homo sapiens (O60704), Homo sapiens
Manually annotated by BRENDA team
Yu, Y.; Hoffhines, A.J.; Moore, K.L.; Leary, J.A.
Determination of the sites of tyrosine O-sulfation in peptides and proteins
Nat. Methods
4
583-588
2007
Homo sapiens (O60507), Homo sapiens (O60704)
Manually annotated by BRENDA team
Ronai, Z.; Witt, H.; Rickards, O.; Destro-Bisol, G.; Bradbury, A.R.; Sahin-Toth, M.
A common African polymorphism abolishes tyrosine sulfation of human anionic trypsinogen (PRSS2)
Biochem. J.
418
155-161
2009
Homo sapiens (O60704), Homo sapiens
Manually annotated by BRENDA team
Jen, C.H.; Moore, K.L.; Leary, J.A.
Pattern and temporal sequence of sulfation of CCR5 N-terminal peptides by tyrosylprotein sulfotransferase-2: an assessment of the effects of N-terminal residues
Biochemistry
48
5332-5338
2009
Homo sapiens
Manually annotated by BRENDA team
Mhidia, R.; Vallin, A.; Ollivier, N.; Blanpain, A.; Shi, G.; Christiano, R.; Johannes, L.; Melnyk, O.
Synthesis of peptide-protein conjugates using N-succinimidyl carbamate chemistry
Bioconjug. Chem.
21
219-228
2010
Homo sapiens
Manually annotated by BRENDA team
Kanan, Y.; Hoffhines, A.; Rauhauser, A.; Murray, A.; Al-Ubaidi, M.R.
Protein tyrosine-O-sulfation in the retina
Exp. Eye Res.
89
559-567
2009
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Stone, M.J.; Chuang, S.; Hou, X.; Shoham, M.; Zhu, J.Z.
Tyrosine sulfation: an increasingly recognised post-translational modification of secreted proteins
N. Biotechnol.
25
299-317
2009
Bos taurus, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Lu, L.; Chen, B.; Wu, J.; Wang, C.; Chen, D.; Yang, Y.
Implantation of post-translational tyrosylprotein sulfation into a prokaryotic expression system
ChemBioChem
12
377-379
2011
Homo sapiens
Manually annotated by BRENDA team
Danan, L.M.; Yu, Z.; Ludden, P.J.; Jia, W.; Moore, K.L.; Leary, J.A.
Catalytic mechanism of Golgi-resident human tyrosylprotein sulfotransferase-2: a mass spectrometry approach
J. Am. Soc. Mass Spectrom.
21
1633-1642
2010
Homo sapiens
Manually annotated by BRENDA team
Teramoto, T.; Fujikawa, Y.; Kawaguchi, Y.; Kurogi, K.; Soejima, M.; Adachi, R.; Nakanishi, Y.; Mishiro-Sato, E.; Liu, M.C.; Sakakibara, Y.; Suiko, M.; Kimura, M.; Kakuta, Y.
Crystal structure of human tyrosylprotein sulfotransferase-2 reveals the mechanism of protein tyrosine sulfation reaction
Nat. Commun.
4
1572
2013
Homo sapiens (O60704), Homo sapiens
Manually annotated by BRENDA team
Zhou, W.; Duckworth, B.P.; Geraghty, R.J.
Fluorescent peptide sensors for tyrosylprotein sulfotransferase activity
Anal. Biochem.
461
1-6
2014
Homo sapiens (O60507), Homo sapiens (O60704), Homo sapiens
Manually annotated by BRENDA team
Marforio, T.D.; Giacinto, P.; Bottoni, A.; Calvaresi, M.
Computational evidence for the catalytic mechanism of tyrosylprotein sulfotransferases: a density functional theory investigation
Biochemistry
54
4404-4410
2015
Homo sapiens (O60704), Homo sapiens
Manually annotated by BRENDA team
Nedumpully-Govindan, P.; Li, L.; Alexov, E.G.; Blenner, M.A.; Ding, F.
Structural and energetic determinants of tyrosylprotein sulfotransferase sulfation specificity
Bioinformatics
30
2302-2309
2014
Homo sapiens (O60507), Homo sapiens (O60704)
Manually annotated by BRENDA team
Hartmann-Fatu, C.; Bayer, P.
Determinants of tyrosylprotein sulfation coding and substrate specificity of tyrosylprotein sulfotransferases in metazoans
Chem. Biol. Interact.
259
17-22
2016
Homo sapiens (O60507), Homo sapiens (O60704)
Manually annotated by BRENDA team
Hartmann-Fatu, C.; Trusch, F.; Moll, C.N.; Michin, I.; Hassinen, A.; Kellokumpu, S.; Bayer, P.
Heterodimers of tyrosylprotein sulfotransferases suggest existence of a higher organization level of transferases in the membrane of the trans-Golgi apparatus
J. Mol. Biol.
427
1404-1412
2015
Homo sapiens
Manually annotated by BRENDA team
Jiang, Z.; Zhu, J.; Ma, Y.; Hong, C.; Xiao, S.; Jin, L.
Tyrosylprotein sulfotransferase 1 expression is negatively correlated with c-Met and lymph node metastasis in human lung cancer
Mol. Med. Rep.
12
5217-5222
2015
Homo sapiens (O60507), Homo sapiens
Manually annotated by BRENDA team
Singh, W.; Karabencheva-Christova, T.; Black, G.; Sparagano, O.; Christov, C.
Conformational flexibility influences structure-function relationships in tyrosyl protein sulfotransferase-2
RSC Adv.
6
11344-11352
2016
Homo sapiens (O60704)
-
Manually annotated by BRENDA team
Singh, W.; Karabencheva-Christova, T.; Sparagano, O.; Black, G.; Petrov, P.; Christov, C.
Dimerization and ligand binding in tyrosylprotein sulfotransferase-2 are influenced by molecular motions
RSC Adv.
6
18542-18548
2016
Homo sapiens (O60704)
-
Manually annotated by BRENDA team
Wang, C.C.; Chen, B.H.; Lu, L.Y.; Hung, K.S.; Yang, Y.S.
Preparation of tyrosylprotein sulfotransferases for in vitro one-pot enzymatic synthesis of sulfated proteins/peptides
ACS Omega
3
11633-11642
2018
Drosophila melanogaster (Q9VYB7), Drosophila melanogaster, Homo sapiens (O60507), Homo sapiens (O60704), Homo sapiens
Manually annotated by BRENDA team
Zhou, W.; Wang, Y.; Xie, J.; Geraghty, R.J.
A fluorescence-based high-throughput assay to identify inhibitors of tyrosylprotein sulfotransferase activity
Biochem. Biophys. Res. Commun.
482
1207-1212
2017
Homo sapiens (O60507), Homo sapiens (O60704)
Manually annotated by BRENDA team
Byrne, D.P.; Li, Y.; Ngamlert, P.; Ramakrishnan, K.; Eyers, C.E.; Wells, C.; Drewry, D.H.; Zuercher, W.J.; Berry, N.G.; Fernig, D.G.; Eyers, P.A.
New tools for evaluating protein tyrosine sulfation tyrosylprotein sulfotransferases (TPSTs) are novel targets for RAF protein kinase inhibitors
Biochem. J.
475
2435-2455
2018
Homo sapiens (O60507), Homo sapiens (O60704)
Manually annotated by BRENDA team
Yeoh, S.; Bayliss, R.
New tools for evaluating protein tyrosine sulfation and carbohydrate sulfation
Biochem. J.
475
3035-3037
2018
Homo sapiens (O60507)
Manually annotated by BRENDA team
Seibert, C.; Sanfiz, A.; Sakmar, T.P.; Veldkamp, C.T.
Preparation and analysis of N-terminal chemokine receptor sulfopeptides using tyrosylprotein sulfotransferase enzymes
Methods Enzymol.
570
357-388
2016
Homo sapiens (O60507), Homo sapiens (O60704)
Manually annotated by BRENDA team
Tanaka, S.; Nishiyori, T.; Kojo, H.; Otsubo, R.; Tsuruta, M.; Kurogi, K.; Liu, M.C.; Suiko, M.; Sakakibara, Y.; Kakuta, Y.
Structural basis for the broad substrate specificity of the human tyrosylprotein sulfotransferase-1
Sci. Rep.
7
8776
2017
Homo sapiens (O60507), Homo sapiens
Manually annotated by BRENDA team