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Information on EC 2.8.2.5 - chondroitin 4-sulfotransferase
for references in articles please use BRENDA:EC2.8.2.5
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EC Tree 2 Transferases
2.8 Transferring sulfur-containing groups
2.8.2 Sulfotransferases
2.8.2.5 chondroitin 4-sulfotransferase
IUBMB Comments
The sulfation takes place at the 4-position of N-acetyl-galactosamine residues of chondroitin. Not identical with EC 2.8.2.17 chondroitin 6-sulfotransferase.
The enzyme appears in viruses and cellular organisms
- 2.8.2.5
- proteoglycans
- glycosaminoglycans
-
sulfotransferases
- keratan
- n-acetylgalactosamine
- 4-sulfate
-
chst15
-
4-o-sulfation
-
6-sulfotransferase
-
uronyl
-
2-o-sulfotransferase
-
iduronic
- medicine
- synthesis
Reaction Schemes
showSynonyms
c4st-1, chst11, carbohydrate sulfotransferase, c4st, chondroitin 4-sulfotransferase, c4st-2, chondroitin 4-o-sulfotransferase-1, chondroitin-4-sulfotransferase, chondroitin 4-o-sulfotransferase, chondroitin sulfotransferase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C41C4.1
C4ST
C4ST-1
C4ST-2
carbohydrate sulfotransferase
Chn 4-O-sulfotransferase
chondroitin 4-O-sulfotransferase
chondroitin 4-O-sulfotransferase-1
chondroitin 4-O-sulfotransferase-2
chondroitin 4-sulfotransferase 1
chondroitin 4-sulfotransferase 2
chondroitin sulfotransferase
-
-
-
-
chondroitin-4-sulfotransferase
chst-1
CHST11
CS-sulfotransferase
sulfotransferase, chondroitin
-
-
-
-
sulfotransferase, chondroitin 4-
-
-
-
-
additional information
-
the enzyme belongs to the chondroitin/dermatan 4-O-sulfotransferase, C4ST/D4ST, family
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3'-phosphoadenylyl sulfate + chondroitin = adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
sulfate group transfer
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
chondroitin sulfate biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
3'-phosphoadenylyl-sulfate:chondroitin 4'-sulfotransferase
The sulfation takes place at the 4-position of N-acetyl-galactosamine residues of chondroitin. Not identical with EC 2.8.2.17 chondroitin 6-sulfotransferase.
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CAS REGISTRY NUMBER
COMMENTARY
83589-04-2
-
9026-07-7
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
3'-phosphoadenylylsulfate + chondroitin sulfate C
adenosine 3',5'-bisphosphate + chondroitin sulfate C 4'-sulfate
3'-phosphoadenylylsulfate + chondroitin sulfate D
adenosine 3',5'-bisphosphate + chondroitin sulfate D 4'-sulfate
Substrates: low activity
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin-derived oligosaccharides
adenosine 3',5'-bisphosphate + mixture of 4'-monosulfated oligosaccharides
3'-phosphoadenylylsulfate + desulfated chondroitin sulfate A
adenosine 3',5'-bisphosphate + chondroitin sulfate A
3'-phosphoadenylylsulfate + desulfated chondroitin sulfate B
adenosine 3',5'-bisphosphate + chondroitin sulfate B
Substrates: low activity
Products: -
Products: -
?
3'-phosphoadenylylsulfate + desulfated dermatan sulfate
adenosine 3',5'-bisphosphate + ?
-
Substrates: 113% of the activity with chondroitin
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Q7T3S3, Q75W66
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Q7T3S3, Q75W66
Substrates: recombinant C4ST-1 shows a substrate preference for chondroitin and catalysed the 4-O-sulfation of GalNAc residues
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: the enzyme is involved in the biosynthesis of dermatan sulfate in addition to chondroitin sulfate intermediates
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + dermatan
adenosine 3',5'-bisphosphate + dermatan 4'-sulfate
-
Substrates: the enzyme is involved in the biosynthesis of dermatan sulfate in addition to chondroitin sulfate intermediates
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + dermatan
adenosine 3',5'-bisphosphate + dermatan 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: involved in biosynthesis of chondroitin sulfate
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: isozyme C4ST1, best substrate
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin sulfate C
adenosine 3',5'-bisphosphate + chondroitin sulfate C 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin sulfate C
adenosine 3',5'-bisphosphate + chondroitin sulfate C 4'-sulfate
Substrates: low activity
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin sulfate C
adenosine 3',5'-bisphosphate + chondroitin sulfate C 4'-sulfate
-
Substrates: low activity
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin-derived oligosaccharides
adenosine 3',5'-bisphosphate + mixture of 4'-monosulfated oligosaccharides
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin-derived oligosaccharides
adenosine 3',5'-bisphosphate + mixture of 4'-monosulfated oligosaccharides
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + desulfated chondroitin sulfate A
adenosine 3',5'-bisphosphate + chondroitin sulfate A
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + desulfated chondroitin sulfate A
adenosine 3',5'-bisphosphate + chondroitin sulfate A
Substrates: low activity
Products: -
Products: -
?
3'-phosphoadenylylsulfate + desulfated chondroitin sulfate A
adenosine 3',5'-bisphosphate + chondroitin sulfate A
-
Substrates: low activity
Products: -
Products: -
?
3'-phosphoadenylylsulfate + desulfated dermatan sulfate
?
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + desulfated dermatan sulfate
?
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + desulfated dermatan sulfate
?
Substrates: i.e. dermatan
Products: -
Products: -
?
3'-phosphoadenylylsulfate + desulfated dermatan sulfate
?
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + desulfated dermatan sulfate
?
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + partially desulfated dermatan sulfate
?
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + partially desulfated dermatan sulfate
?
Substrates: isozyme C4ST2, best substrate
Products: -
Products: -
?
3'-phosphoadenylylsulfate + partially desulfated dermatan sulfate
?
Substrates: isozyme C4ST3, very low activity
Products: -
Products: -
?
additional information
?
-
Substrates: C4ST-1 also shows activity with partially desulfated dermatan sulfate, strong preference of zebrafish C4ST-1 for the sequence -GlcA-GalNAc(4S)-GlcA- over -IdoA-GalNAc(4S)-IdoA-
Products: -
Products: -
?
additional information
?
-
Q75W66
Substrates: C4ST-1 also shows activity with partially desulfated dermatan sulfate, strong preference of zebrafish C4ST-1 for the sequence -GlcA-GalNAc(4S)-GlcA- over -IdoA-GalNAc(4S)-IdoA-
Products: -
Products: -
?
additional information
?
-
-
Substrates: C4ST-1 also shows activity with partially desulfated dermatan sulfate, strong preference of zebrafish C4ST-1 for the sequence -GlcA-GalNAc(4S)-GlcA- over -IdoA-GalNAc(4S)-IdoA-
Products: -
Products: -
?
additional information
?
-
Substrates: C4ST-2 also shows activity with partially desulfated dermatan sulfate
Products: -
Products: -
?
additional information
?
-
Q75W66
Substrates: C4ST-2 also shows activity with partially desulfated dermatan sulfate
Products: -
Products: -
?
additional information
?
-
-
Substrates: C4ST-2 also shows activity with partially desulfated dermatan sulfate
Products: -
Products: -
?
additional information
?
-
Substrates: product structure analysis
Products: -
Products: -
?
additional information
?
-
Substrates: product structure analysis
Products: -
Products: -
?
additional information
?
-
Substrates: product structure analysis
Products: -
Products: -
?
additional information
?
-
-
Substrates: product structure analysis
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with dermatan sulfate, keratan sulfate
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with dermatan sulfate, keratan sulfate
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with dermatan sulfate, keratan sulfate
Products: -
Products: -
?
additional information
?
-
Substrates: chondroitin sulfate E is no substrate
Products: -
Products: -
?
additional information
?
-
Substrates: chondroitin sulfate E is no substrate
Products: -
Products: -
?
additional information
?
-
Substrates: chondroitin sulfate E is no substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: chondroitin sulfate E is no substrate
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with desulfated and N-sulfated heparin, and desulfated and N-acetylated heparin
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with desulfated and N-sulfated heparin, and desulfated and N-acetylated heparin
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with desulfated and N-sulfated heparin, and desulfated and N-acetylated heparin
Products: -
Products: -
?
additional information
?
-
-
Substrates: no substrate: chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate. Enzyme mainly transfers sulfate to position 4 of the GalNAc residue located at the GlcA-GalNAc-GlcA sequence
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is required for proper chondroitin sulfate localization, modulation of distinct signaling pathways and cartilage growth plate morphogenesis
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme regulates E disaccharide expression of chondroitin sulfate required for Herpes simplex virus infectivity in mouse cells, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: chondroitin 4-sulfotransferase-1 and -2, which catalyze the 4-O-sulfation of nonsulfated GalNAc residues
Products: -
Products: -
?
additional information
?
-
-
Substrates: chondroitin 4-sulfotransferase-1 and -2, which catalyze the 4-O-sulfation of nonsulfated GalNAc residues
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with dermatan sulfate, keratan sulfate
Products: -
Products: -
?
additional information
?
-
-
Substrates: chondroitin sulfate E, heparan sulfate, and completely desulfated N-resulfated heparin are no acceptor substrates
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
3'-phosphoadenylyl sulfate + dermatan
adenosine 3',5'-bisphosphate + dermatan 4'-sulfate
-
Substrates: the enzyme is involved in the biosynthesis of dermatan sulfate in addition to chondroitin sulfate intermediates
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Q7T3S3, Q75W66
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylyl sulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: the enzyme is involved in the biosynthesis of dermatan sulfate in addition to chondroitin sulfate intermediates
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: involved in biosynthesis of chondroitin sulfate
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
3'-phosphoadenylylsulfate + chondroitin
adenosine 3',5'-bisphosphate + chondroitin 4'-sulfate
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is required for proper chondroitin sulfate localization, modulation of distinct signaling pathways and cartilage growth plate morphogenesis
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme regulates E disaccharide expression of chondroitin sulfate required for Herpes simplex virus infectivity in mouse cells, overview
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Detergents
-
with the exception of Triton X-100 and Nonidet P-40, inhibit sulfation in the mast cell system
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
stimulation by basic substances is much higher than that by Mn2+, however increasing Mn2+ concentration immediately reduces the stimulation by basic substances
-
protamine
-
molar ratio of protamine to repeating disaccharide unit of chondroitin is 1:100
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Molecular cloning, expression, and chromosomal mapping of human chondroitin 4-sulfotransferase, whose expression pattern in human tissues is different from that of chondroitin 6-sulfotransferase.
Adenocarcinoma
Prognostic impact of carbohydrate sulfotransferase 15 in patients with pancreatic ductal adenocarcinoma.
Atherosclerosis
Correlation of C4ST-1 and ChGn-2 expression with chondroitin sulfate chain elongation in atherosclerosis.
Brain Injuries, Traumatic
Decline in arylsulfatase B and Increase in chondroitin 4-sulfotransferase combine to increase chondroitin 4-sulfate in traumatic brain injury.
Breast Neoplasms
Carbohydrate (Chondroitin 4) Sulfotransferase-11-Mediated Induction of Epithelial-Mesenchymal Transition and Generation of Cancer Stem Cells.
Breast Neoplasms
Chondroitin sulfates play a major role in breast cancer metastasis: a role for CSPG4 and CHST11 gene expression in forming surface P-selectin ligands in aggressive breast cancer cells.
Breast Neoplasms
Cleavage of Syndecan-1 Promotes the Proliferation of the Basal-Like Breast Cancer Cell Line BT-549 Via Akt SUMOylation.
Breast Neoplasms
Long noncoding RNA HOTAIR promotes invasion of breast cancer cells through chondroitin sulfotransferase CHST15.
Carcinoma, Hepatocellular
Carbohydrate Sulfotransferase 4 Inhibits the Progression of Hepatitis B Virus-Related Hepatocellular Carcinoma and Is a Potential Prognostic Marker in Several Tumors.
Cardiomyopathy, Dilated
Small interfering RNA therapy against carbohydrate sulfotransferase 15 inhibits cardiac remodeling in rats with dilated cardiomyopathy.
chondroitin 4-sulfotransferase deficiency
Inherited CHST11/MIR3922 deletion is associated with a novel recessive syndrome presenting with skeletal malformation and malignant lymphoproliferative disease.
Chondrosarcoma
Chondroitin 4-sulphotransferase-1 and chondroitin 6-sulphotransferase-1 are affected differently by uronic acid residues neighbouring the acceptor GalNAc residues.
Chondrosarcoma
N-linked oligosaccharides are required to produce and stabilize the active form of chondroitin 4-sulphotransferase-1.
Chondrosarcoma
Purification and characterization of chondroitin 4-sulfotransferase from the culture medium of a rat chondrosarcoma cell line.
Colitis
Pivotal Role of Carbohydrate Sulfotransferase 15 in Fibrosis and Mucosal Healing in Mouse Colitis.
Corneal Dystrophies, Hereditary
Different mutations in carbohydrate sulfotransferase 6 (CHST6) gene cause macular corneal dystrophy types I and II in a single sibship.
Corneal Dystrophies, Hereditary
Identification of novel mutations in the carbohydrate sulfotransferase gene (CHST6) causing macular corneal dystrophy.
Corneal Dystrophies, Hereditary
Impairment of the autophagy-lysosomal pathway and activation of pyroptosis in macular corneal dystrophy.
Corneal Dystrophies, Hereditary
In vivo laser confocal microscopic findings of corneal stromal dystrophies.
Corneal Dystrophies, Hereditary
Localization and expression of CHST6 and keratan sulfate proteoglycans in the human cornea.
Corneal Dystrophies, Hereditary
Macular corneal dystrophy in a Chinese family related with novel mutations of CHST6.
Corneal Dystrophies, Hereditary
Mutation analysis of CHST6 gene in Chinese patients with macular corneal dystrophy.
Corneal Dystrophies, Hereditary
Mutation analysis of the carbohydrate sulfotransferase gene in Vietnamese with macular corneal dystrophy.
Corneal Dystrophies, Hereditary
Mutations in corneal carbohydrate sulfotransferase 6 gene (CHST6) cause macular corneal dystrophy in Iceland.
Corneal Dystrophies, Hereditary
Novel CHST6 Gene Mutations in 2 Unrelated Cases of Macular Corneal Dystrophy.
Corneal Dystrophies, Hereditary
Novel CHST6 nonsense and missense mutations responsible for macular corneal dystrophy.
Corneal Dystrophies, Hereditary
Novel compound heterozygous mutations in the CHST6 gene cause macular corneal dystrophy in a Han Chinese family.
Corneal Dystrophies, Hereditary
Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy.
Corneal Dystrophies, Hereditary
Novel mutations in the CHST6 gene associated with macular corneal dystrophy in southern India.
Corneal Dystrophies, Hereditary
Novel mutations in the CHST6 gene causing macular corneal dystrophy.
Corneal Dystrophies, Hereditary
Novel mutations of CHST6 in Iranian patients with macular corneal dystrophy.
Corneal Dystrophies, Hereditary
Phenotype and genotype analysis in patients with macular corneal dystrophy.
Corneal Dystrophies, Hereditary
Sequencing of the CHST6 gene in Czech macular corneal dystrophy patients supports the evidence of a founder mutation.
Corneal Dystrophies, Hereditary
Truncating mutations in the carbohydrate sulfotransferase 6 gene (CHST6) result in macular corneal dystrophy.
Costello Syndrome
C4ST-1/CHST11-controlled chondroitin sulfation interferes with oncogenic HRAS signaling in Costello syndrome.
Esophageal Stenosis
Prevention of esophageal stricture after endoscopic submucosal dissection using RNA-based silencing of carbohydrate sulfotransferase 15 in a porcine model.
Glioblastoma
Knockdown of carbohydrate sulfotransferase 12 decreases the proliferation and mobility of glioblastoma cells via the WNT/?-catenin pathway.
Hepatitis B
Carbohydrate Sulfotransferase 4 Inhibits the Progression of Hepatitis B Virus-Related Hepatocellular Carcinoma and Is a Potential Prognostic Marker in Several Tumors.
Herpes Simplex
Chondroitin 4-O-sulfotransferase-1 regulates E disaccharide expression of chondroitin sulfate required for herpes simplex virus infectivity.
Infections
Chondroitin 4-O-sulfotransferase-1 regulates E disaccharide expression of chondroitin sulfate required for herpes simplex virus infectivity.
Infections
Cloning and characterization of chst11 from Procambarus clarkii involved in the host immune response of white spot syndrome virus and Aeromonas hydrophila.
Lung Neoplasms
Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations.
Malaria
Natural frequency of polymorphisms linked to the chondroitin 4-sulfotransferase genes and its association with placental malaria.
Melanoma
Mechanism of regulation and suppression of melanoma invasiveness by novel retinoic acid receptor-gamma target gene carbohydrate sulfotransferase 10.
Neoplasm Metastasis
Chondroitin sulfates play a major role in breast cancer metastasis: a role for CSPG4 and CHST11 gene expression in forming surface P-selectin ligands in aggressive breast cancer cells.
Neoplasm Metastasis
CHST11/13 Regulate the Metastasis and Chemosensitivity of Human Hepatocellular Carcinoma Cells Via Mitogen-Activated Protein Kinase Pathway.
Neoplasms
Carbohydrate (Chondroitin 4) Sulfotransferase-11-Mediated Induction of Epithelial-Mesenchymal Transition and Generation of Cancer Stem Cells.
Neoplasms
Carbohydrate Sulfotransferase 4 Inhibits the Progression of Hepatitis B Virus-Related Hepatocellular Carcinoma and Is a Potential Prognostic Marker in Several Tumors.
Neoplasms
Cleavage of Syndecan-1 Promotes the Proliferation of the Basal-Like Breast Cancer Cell Line BT-549 Via Akt SUMOylation.
Neoplasms
Deregulation of the carbohydrate (chondroitin 4) sulfotransferase 11 (CHST11) gene in a B-cell chronic lymphocytic leukemia with a t(12;14)(q23;q32).
Neoplasms
Discovery of Carbohydrate Sulfotransferase Inhibitors from a Kinase-Directed Library We thank Sharon Long and Dave Keating for providing both the NodH sulfotransferase and APS Kinase during our preliminary experiments and Jack Kirsch for numerous helpful conversations. J.I.A. and K.G.B were supported by NIH Molecular Biophysics Training Grant (No. T32GM0895). This research was funded by grants to C.R.B. from the Pew Scholars Program, the W. M. Keck Foundation and the American Cancer Society (Grant No. RPG9700501BE).
Neoplasms
Effects of EUS-guided intratumoral injection of oligonucleotide STNM01 on tumor growth, histology, and overall survival in patients with unresectable pancreatic cancer.
Neoplasms
Inherited CHST11/MIR3922 deletion is associated with a novel recessive syndrome presenting with skeletal malformation and malignant lymphoproliferative disease.
Neoplasms
Inhibition of Cell Proliferation and Growth of Pancreatic Cancer by Silencing of Carbohydrate Sulfotransferase 15 In Vitro and in a Xenograft Model.
Neoplasms
Knockdown of carbohydrate sulfotransferase 12 decreases the proliferation and mobility of glioblastoma cells via the WNT/?-catenin pathway.
Neoplasms
Prognostic impact of carbohydrate sulfotransferase 15 in patients with pancreatic ductal adenocarcinoma.
Osteoarthritis, Hip
Functional Characterization of the Osteoarthritis Susceptibility Mapping to CHST11-A Bioinformatics and Molecular Study.
Ovarian Neoplasms
Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer.
Pancreatic Neoplasms
Effects of EUS-guided intratumoral injection of oligonucleotide STNM01 on tumor growth, histology, and overall survival in patients with unresectable pancreatic cancer.
Pancreatic Neoplasms
Inhibition of Cell Proliferation and Growth of Pancreatic Cancer by Silencing of Carbohydrate Sulfotransferase 15 In Vitro and in a Xenograft Model.
Pancreatic Neoplasms
Overexpression of carbohydrate sulfotransferase 15 in pancreatic cancer stroma is associated with worse prognosis.
Pneumonia
Serum carbohydrate sulfotransferase 7 in lung cancer and non-malignant pulmonary inflammations.
Pulmonary Fibrosis
Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development.
Spinal Cord Injuries
Transcriptional regulation of scar gene expression in primary astrocytes.
Vision Disorders
Localization and expression of CHST6 and keratan sulfate proteoglycans in the human cornea.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00125
3'-phosphoadenylyl sulfate
pH 7.0, 37°C, recombinant enzyme expressed in Escherichia coli
0.036
3'-phosphoadenylyl sulfate
pH 7.0, 37°C, recombinant enzyme expressed in Pichia pastoris
0.0011
3'-phosphoadenylylsulfate
-
pH 6.8, 37°C, mutant with deletion of C-terminal glycosylation site
0.0038
chondroitin
pH 7.0, 37°C, recombinant enzyme expressed in Escherichia coli
0.157
chondroitin
pH 7.0, 37°C, recombinant enzyme expressed in Pichia pastoris
2.7
chondroitin
-
pH 6.8, 37°C, mutant with deletion of C-terminal glycosylation site
additional information
additional information
two-substrate Michaelis-Menten kinetic analysis
-
additional information
additional information
-
two-substrate Michaelis-Menten kinetic analysis
-
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
recombinant enzyme activity with chondroitin and partially desulfated dermatan sulfate
additional information
Q75W66
recombinant enzyme activity with chondroitin and partially desulfated dermatan sulfate
additional information
-
recombinant enzyme activity with chondroitin and partially desulfated dermatan sulfate
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5
6.8
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
28
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
isozyme C4ST3 shows very poor activity with chondroitin and partially desulfated dermatan sulfate as substrates at 37°C compared to 28°C
additional information
isozyme C4ST3 shows very poor activity with chondroitin and partially desulfated dermatan sulfate as substrates at 37°C compared to 28°C
additional information
isozyme C4ST3 shows very poor activity with chondroitin and partially desulfated dermatan sulfate as substrates at 37°C compared to 28°C
additional information
-
isozyme C4ST3 shows very poor activity with chondroitin and partially desulfated dermatan sulfate as substrates at 37°C compared to 28°C
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
bone marrow-derived mast cell, 200fold higher expression of mC4ST-1 than in bone marrow cell
brenda
isozyme C4ST3, high content in adult, low content in fetal liver
brenda
additional information
-
C4ST-2 expression occurs in the early stage bone marrow cell cultures, the process of mast cell maturation does not alter the expression, low expression at day 0, followed by an increase in expression at later stages of culture
brenda
-
C4ST-2 expression occurs in the early stage bone marrow cell cultures, the process of mast cell maturation does not alter the expression, low expression at day 0, followed by an increase in expression at later stages of culture
-
brenda
-
C4ST-1 and C4ST-2 are ubiquitously expressed in the postnatal mouse brain, tissue distribution of expression, overview
brenda
-
developed from bone marrow cells isolated from femur and tibia from C57BL/6 mice, mast cell maturation strongly correlates with the expression of C4ST-1
brenda
-
developed from bone marrow cells isolated from femur and tibia from C57BL/6 mice, mast cell maturation strongly correlates with the expression of C4ST-1
-
brenda
ventricular zone of the dorsal and the ventral telencephalon
brenda
additional information
C4ST-1 is predominantly expressed in spleen, thymus, bone marrow, peripheral blood leukocytes, lymph node, heart, brain, lung, and placenta
brenda
additional information
-
C4ST-1 is predominantly expressed in spleen, thymus, bone marrow, peripheral blood leukocytes, lymph node, heart, brain, lung, and placenta
brenda
additional information
analysis of the content of chondroitin sulfate (CS) in the cells, disaccharide composition analysis of CS, the expression level of CS is expressed as total amounts of unsaturated disaccharides, overview
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
secretion into the medium is supported by ascorbic acid and inhibited by monensin
-
brenda
-
secreted to the extracellular space in a soluble form under the culture conditions
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
there are three major C4ST isoforms in Homo sapiens, C4ST-1, C4ST-2, and C4ST-3. Based on a general amino acid sequence analysis, C4STs contain a single cytoplasmic domain followed by helical transmembrane domain and a lumenal domain. C4ST-1 has two additional variants, and both are capable of sulfating unsulfated chondroitin and dermatan with a preference of D-glucuronic acid (GlcA)->GalNAc over L-iduronic acid (IdoA)->GalNAc. C4ST-2 has a lower activity towards unsulfated dermatan than does C4ST-1
malfunction
metabolism
physiological function
additional information
-
dominant disaccharide species in both disc and arm samples are the di-O-sulfated DELTAHexA(2S)1-3GalNAc(4S) and DELTAHexA(2S)1-3GalNAc(6S), and the tri-O-sulfated disaccharide DELTAHexA(2S)1-3GalNAc(4,6S), while only small amounts of mono-O-sulfated disaccharides (DELTAHexA1-3GalNAc(4S), DELTAHexA1-3GalNAc(6S), and DELTAHexA(2S)1-3GalNAc(2S)) are recovered. The relative distribution of the different disaccharide species indicates a predominance of the tri-O-sulfated units in arms while the disc part contains proportionally more of the di-O-sulfated DELTAHexA(2S)1-3GalNAc(4S) disaccharide. Overall sulfation of arm CS/DS is about 2.4 sulfate groups/disaccharide, while the overall recovery of CS/DS is similar for disc and arms
malfunction
enzyme deletion mutants exhibit reduced survival rates after synchronization with sodium hypochlorite
malfunction
even though C4ST-1 and C4ST-2 exhibit broad and overlapping mRNA expression patterns, indicating the functional redundancy of these enzymes, a deficiency or experimental knockdown of C4ST-1 results in a dramatic decrease of cellular and whole-body levels of chondroitin 4'-sulfate. The enzyme completely loses activity when deglycosylated by treatment with PNGase F
malfunction
the ratio of 4-O-sulfation to 6-O-sulfation (4S/6S) and CS chain length, that occur during the aging process, are decreased in polyamine-depleted cells. In addition, decreased levels of chondroitin synthase 1 (CHSY1, EC 2.4.1.175) and chondroitin 4-O-sulfotransferase 2 proteins are also observed on polyamine depletion. The destabilization of G4 structures by polyamines (i.e. putrescine, spermidine and spermine) stimulates CHSY1 synthesis and, at least in part, contributes to the maturation of CS chains
malfunction
C4ST-1 activity and C4S production are upregulated in human glioma tissues, when compared to normal brain tissue, and the extent of upregulation positively correlates with glioma malignancy. Inhibition of expression of the two CS synthetic enzymes chondroitin 4-O-sulfotransferase-1 (C4ST-1/CHST11) and chondroitin 6-O-sulfotransferase-1 (C6ST-1/CHST3, EC 2.8.2.17) suppress cell viability, migration and invasion, reduce MMP-2 and MMP-9 expression, and reduce N-cadherin expression, but increase E-cadherin levels. Clinicopathological features, overview
malfunction
-
enzyme deletion mutants exhibit reduced survival rates after synchronization with sodium hypochlorite
-
metabolism
-
the enzyme plays a key role in regulating levels of chondroitin sulfate synthesized via chondroitin N-acetylgalactosaminyltransferase-1
metabolism
-
the enzyme regulates the length and amount of chondroitin sulfate chains in co-operation with chondroitin N-acetylgalactosaminyltransferase 2
metabolism
C4ST-1 is believed to play a distinct regulatory role not only in CS 4-O-sulfation but also in the amount of CS synthesis since none of the other family member C4ST-2 and C4ST-3 can compensate for the loss of C4ST-1
metabolism
chondroitin sulfate (CS) biosynthesis is initiated once GalNAc is transferred by CSGalNAcT1 or 2 to the common linkage tetrasaccharide, GlcAbeta1-3galactose (Gal)beta1-3Galbeta1-4xylose (Xyl)beta1-O-serine in proteoglycans and chain elongation is then catalyzed by the chondroitin synthase (CHSY) 1-3/chondroitin-polymerizing factor (CHPF) heterodimer. After synthase-catalyzed polymerization, the majority of the GalNAc residues are 4-O-sulfated by chondroitin 4-O-sulfotransferases (C4ST1, 2 and 3) or 6-O-sulfated by chondroitin 6-O-sulfotransferases (C6ST1 and 2). In addition, resulting A- or C-unit can be further sulfated by GalNAc 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) or chondroitin uronyl 2-O-sulfotransferase (UST), generating di-sulfated disaccharides, E-unit or D-unit, respectively. Structural changes in CS, particularly the ratio of 4-O-sulfation to 6-O-sulfation (4S/6S), occur during normal embryonic development, during growth, and in aging. For example, the 4S/6S ratios of CS (or DS) present in human skin and cartilage decrease from birth to age 20
physiological function
Q7T3S3, Q75W66
chondroitin 4-O-sulfotransferase-1 is required for somitic muscle development and motor axon guidance in zebrafish
physiological function
the enzyme plays an important role in protecting nematodes from oxidative stress
physiological function
chondroitin sulfates are linear sulfated polysaccharides called glycosaminoglycans. They are important nutraceutical and pharmaceutical products that are biosynthesized through the action of chondroitin sulfotransferases on either an unsulfated chondroitin or a dermatan polysaccharide precursor. The major chondroitin-4-sulfotransferase in Homo sapiens is C4ST-1
physiological function
-
potential role for chondroitin sulfate/dermatan sulfate in arm regeneration in Amphiura filiformis, increased sulfation of CS/DS during arm regeneration is observed. Based on the structural changes observed during arm regeneration, chondroitin synthase, chondroitin-4-O-sulfotransferase 2, and dermatan-4-O-sulfotransferase are identified as candidate genes correlating their expression with the expression of the Amphiura filiformis orthologue of bone morphogenetic factors, AfBMP2/4. Quantitative amplification by real-time PCR indicates increased expression of chondroitin synthase and chondroitin-4-O-sulfotransferase 2, with a corresponding increase in AfBMP2/4 during regeneration relative to nonregenerating controls. Proper sulfation of glycosaminoglycans (GAGs), such as chondroitin sulfate (CS) and dermatan sulfate (DS), is important for Amphiura filiformis arm regeneration. The molecules may participate in mechanisms controlling cell proliferation. Role of CS/DS in the regeneration process
physiological function
key molecules promoting migration and invasion exist in the extracellular matrix, and include chondroitin 4-sulfate (C4S) and chondroitin 6-sulfate (C6S), functionally important carbohydrate chains of chondroitin sulfate proteoglycans that participate in regulating cancer development. The C4S- and C6S-enhanced epithelial-tomesenchymal transition and expression of MMP-2 occur via activation of the PI3K/AKT signaling pathway, known to be involved in promoting cell migration and invasion. C4S and C6S increase the numbers of living glioma cells and promote proliferation, they promote colony formation of glioma cells, phenotypes, overview
physiological function
-
the enzyme plays an important role in protecting nematodes from oxidative stress
-
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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). CHSTB_RAT
352
1
41626
Swiss-Prot
other Location (Reliability: 3)
CHSTD_HUMAN
341
1
38920
Swiss-Prot
Mitochondrion (Reliability: 5)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
-
the deglycosylated enzyme forms dimers in solution of 70 kDa
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
four potential glycosylation sites in human C4ST-1: Asn205, Asn223, Asn321, and Asn342. Enzyme C4ST-1 requires glycosylation for its activity. The enzyme completely loses activity when deglycosylated by treatment with PNGase F. In particular, the glycosylation site Asn342 near the C-terminus is believed to be essential to the activity of C4ST-1 since the mutant devoid of this site lost significant activity compared to the wild-type enzyme. Asn223 and Asn342 are thought to contribute mainly to the stability of the protein rather than to the production of the active enzyme. The recombinant glycosylated form of C4ST-1 shows lower stability than the non-glycosylated form
glycoprotein
-
contains about 35% N-linked oligosaccharides, treatment of enzyme with peptide N-glycosidase F causes a marked decrease in activity, production of active form of recombinant enzyme is inhibited by tunicamycin
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
functional knockdown of C4ST-1 with specific antisense morpholino-oligonucleotides leads to a marked decrease in the 4-O-sulfation and amount of chondroitin sulfate in the embryos. Consistent with the preferential expression in the rostrocaudal axis, C4ST-1 morphants display morphological defects exemplified by a ventrally bent trunk and a curled and/or kinky tail, largely due to misregulated myotomal myod expression, implying perturbation of axial muscle differentiation in somites. Rescue of morphological phenotypes of the MO1-injected embryos by injection with zebrafish C4ST-1 RNA, phenotypes, overview
additional information
Q75W66
functional knockdown of C4ST-1 with specific antisense morpholino-oligonucleotides leads to a marked decrease in the 4-O-sulfation and amount of chondroitin sulfate in the embryos. Consistent with the preferential expression in the rostrocaudal axis, C4ST-1 morphants display morphological defects exemplified by a ventrally bent trunk and a curled and/or kinky tail, largely due to misregulated myotomal myod expression, implying perturbation of axial muscle differentiation in somites. Rescue of morphological phenotypes of the MO1-injected embryos by injection with zebrafish C4ST-1 RNA, phenotypes, overview
additional information
-
functional knockdown of C4ST-1 with specific antisense morpholino-oligonucleotides leads to a marked decrease in the 4-O-sulfation and amount of chondroitin sulfate in the embryos. Consistent with the preferential expression in the rostrocaudal axis, C4ST-1 morphants display morphological defects exemplified by a ventrally bent trunk and a curled and/or kinky tail, largely due to misregulated myotomal myod expression, implying perturbation of axial muscle differentiation in somites. Rescue of morphological phenotypes of the MO1-injected embryos by injection with zebrafish C4ST-1 RNA, phenotypes, overview
additional information
-
translocations t(12,14)(q23,q32) in a patient with B-cell chronic lymphocytic leukemia result in expression of two truncated forms of enzyme protein, resulting in disturbance of the cellular distribution of enzyme, and further in deregulation of a chondroitin-sulfate dependent pathway specific to the hematopoietic lineage
additional information
-
gene-trap mutation in bone morphogenic protein-induced enzyme causes severe chondrodysplasia characterised by disorganised cartilage growth plate as well as specific alterations in the orientation of chondrocyte columns. Phenotype is associated with chondroitin sulfation imbalance, mislocalization of chondroitin sulfate and imbalance of apoptotic signals
additional information
-
CS-deficient sog9 cells, derived from gro2C cells partially resistant to HSV-1 infection and defective in the expression of heparan sulfate because of a splice site mutation in the EXT1 gene encoding the HS-synthesizing enzyme, have a defect in the expression of C4ST-1 in addition to EXT1, decrease in the amount of chondroitin sulfate in sog9 cells is the result of a reduction in the length of chondroitin sulfate chains, glycosyltransferases participating in the biosynthesis of chondroitin sulfate are not affected in sog9 cells, rescue of sog9 cells only by introducing C4ST-1
additional information
-
deletion of N-glycosylation sites, loss of the N-glycosylation site at the C-terminus reduces activity by 80%
additional information
reconstitution of the chondroitin biosynthesis pathway in a recombinant Bacillus subtilis strain using sucrose as carbon source, method optimization, overview. Specific sulfation transformation systems are successfully constructed and optimized by combining the purified aryl sulfotransferase IV (ASST IV, EC 2.8.2.1), chondroitin 4-sulfotransferase (C4ST) and chondroitin 6-sulfotransferase (C6ST, EC 2.8.2.17). Chondroitin sulfate A and C are enzymatically transformed from chondroitin at conversion rates of 98% and 96%, respectively. The ASST IV enzyme is used for PAPS regeneration. Purification of CS disaccharides by anion exchange chrmatography and NMR analysis of the composition of CS disaccharides
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged C4ST-1 from Escherichia coli strain BL21 Star(DE3) by nickel affinity chromatography
sephadex G-25 chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA sequence determination and analysis, chromosome mapping at p22 region of chromosome 7, expression in CHO cells
DNA sequence determination and analysis, located on chromosome 3, genomic organisation, expression as myc- and His-tagged enzyme in CHO cells
DNA sequence dtermination and analysis, chromosome mapping at q23 region of chromosome 12, expression in CHO cells
expression as N-terminally truncated enzyme, lacking the first 57 amino acids, in COS-1 cells
expression as N-terminally truncated enzyme, lacking the first 76 amino acids, in COS-1 cells
gene C4ST, recombinant expression in Bacillus subtilis strain E168C, Escherichia coli strain BL21(DE3), and Pichia pastoris strain GS115, coexpression with ASSTIV and C6ST from Rattus norvegicus, subcloning in Escherichia coli strain JM109. Chondroitin extraction and quantification
gene C4ST-1, DNA and amino acid sequence determination and analysis, sequence comparison and phylogenetic analysis
Q7T3S3, Q75W66
gene C4ST-2, DNA and amino acid sequence determination and analysis, sequence comparison and phylogenetic analysis
Q7T3S3, Q75W66
genetic library screening, DNA and amino acid sequence determination and analysis, transient functional overexpression of wild-type and FLAG-tagged enzyme in COS-7 cells, control expression of C4ST in antisense orientation
recombinant expression of non-glycosylated and glycosylated His6-tagged C4ST-1 construct in Escherichia coli strain BL21 Star(DE3), recombinant expression in Pichia pastoris strain ATCC 76273, both in its non-glycosylated and glycosylated forms, leads to an unstable enzyme. Glycosylation of the yeast-expressed sulfotransferase does not improve its overall stability. The activity of the purified Pichia pastoris expressing C4ST-1 is completely lost after 72 h
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
a decline in arylsulfatase B reduces chondroitin-4-sulfotransferase mRNA expression. Inhibition of bone morphogenetic protein 4 also reduces enzyme expression
a significantly higher mRNA expression of CHST11 is measured in ovarian cancer samples in comparison to non-malignant ones
A23187 causes a down-regulated expression of the C4ST-2 gene with 50% reduction after 1 h, followed by return to basal levels after 4.5 h
polyamines stimulate the synthesis of C4ST2 in HCT-116 cells, C4ST2 is stimulated at the transcriptional level
silencing Wnt9A increases the expression of CHST11
the expression levels of C4ST2 mRNA and protein decrease in DFMO-treated HCT-116 cells
the suppression of enzyme gene expression by Wnt/b-etacatenin signaling can be recovered by treatment with trichostatin A
a decline in arylsulfatase B reduces chondroitin-4-sulfotransferase mRNA expression. Inhibition of bone morphogenetic protein 4 also reduces enzyme expression
a decline in arylsulfatase B reduces chondroitin-4-sulfotransferase mRNA expression. Inhibition of bone morphogenetic protein 4 also reduces enzyme expression
A23187 causes a down-regulated expression of the C4ST-2 gene with 50% reduction after 1 h, followed by return to basal levels after 4.5 h
-
A23187 causes a down-regulated expression of the C4ST-2 gene with 50% reduction after 1 h, followed by return to basal levels after 4.5 h
-
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
synthesis
the enzyme is used for large scale chondroitin sulfate synthesis in a coupled system with aryl sulfotransferase IV and chondroitin 6-sulfotransferase, overview
medicine
-
gene-trap mutation in bone morphogenic protein-induced enzyme causes severe chondrodysplasia characterised by disorganised cartilage growth plate as well as specific alterations in the orientation of chondrocyte columns. Phenotype is associated with chondroitin sulfation imbalance, mislocalization of chondroitin sulfate and imbalance of apoptotic signals
medicine
-
translocations t(12,14)(q23,q32) in a patient with B-cell chronic lymphocytic leukemia result in expression of two truncated forms of enzyme protein, resulting in disturbance of the cellular distribution of enzyme, and further in deregulation of a chondroitin-sulfate dependent pathway specific to the hematopoietic lineage
medicine
the enzyme is an independent unfavorable prognostic factor for ovarian cancer progression
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Habuchi, O.; Miyashita, N.
Separation and characterization of chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase from chick embryo cartilage
Biochim. Biophys. Acta
717
414-421
1982
Gallus gallus
brenda
Sugumaran, G.; Silbert, J.E.
Sulfation of chondroitin. Specificity, degree of sulfation, and detergent effects with 4-sulfating and 6-sulfating microsomal systems
J. Biol. Chem.
263
4673-4678
1988
Mus musculus
brenda
Sugumaran, G.; Cogburn, J.N.; Silbert, J.E.
Simultaneous sulfation of endogenous chondroitin sulfate and chondroitin-derived oligosaccharides. Studies with separate 4-sulfating and 6-sulfating microsomal systems
J. Biol. Chem.
261
12659-12664
1986
Mus musculus
brenda
Habuchi, O.; Tsuzuki, M.; Takeuchi, I.; Hara, M.; Matsui, Y.; Ashikari, S.
Secretion of chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase from cultured chick embryo chondrocytes
Biochim. Biophys. Acta
1133
9-16
1991
Gallus gallus
brenda
Delfert, D.M.; Conrad, H.E.
Sulfation of chondroitin oligosaccharides in vitro. Analysis of sulfation ratios
J. Biol. Chem.
260
14446-14451
1985
Gallus gallus
brenda
Habuchi, O.; Miyata, K.
Stimulation of glycosaminoglycan sulfotransferase from chick embryo cartilage by basic proteins and polyamines
Biochim. Biophys. Acta
616
208-217
1980
Gallus gallus
brenda
Yamauchi, S.; Hirahara, Y.; Usui, H.; Takeda, Y.; Hoshino, M.; Fukuta, M.; Kimura, J.H.; Habuchi, O.
Purification and characterization of chondroitin 4-sulfotransferase from the culture medium of a rat chondrosarcoma cell line
J. Biol. Chem.
274
2456-2463
1999
Rattus norvegicus
brenda
Hiraoka, N.; Nakagawa, H.; Ong, E.; Akama, T.O.; Fukuda, M.N.; Fukuda, M.
Molecular cloning and expression of two distinct human chondroitin 4-O-sulfotransferases that belong to the HNK-1 sulfotransferase gene family
J. Biol. Chem.
275
20188-20196
2000
Homo sapiens (Q9NPF2), Homo sapiens (Q9NRB3), Homo sapiens
brenda
Yamauchi, S.; Mita, S.; Matsubara, T.; Fukuta, M.; Habuchi, H.; Kimata, K.; Habuchi, O.
Molecular cloning and expression of chondroitin 4-sulfotransferase
J. Biol. Chem.
275
8975-8981
2000
Mus musculus (Q9JME2), Mus musculus
brenda
Kang, H.G.; Evers, M.R.; Xia, G.; Baenziger, J.U.; Schachner, M.
Molecular cloning and characterization of chondroitin-4-O-sulfotransferase-3. A novel member of the HNK-1 family of sulfotransferases
J. Biol. Chem.
277
34766-34772
2002
Homo sapiens (Q9NPF2), Homo sapiens (Q9NRB3), Homo sapiens (Q8NET6), Homo sapiens
brenda
Mikami, T.; Mizumoto, S.; Kago, N.; Kitagawa, H.; Sugahara, K.
Specificities of three distinct human chondroitin/dermatan N-acetylgalactosamine 4-O-sulfotransferases demonstrated using partially desulfated dermatan sulfate as an acceptor. Implication of differential roles in dermatan sulfate biosynthesis
J. Biol. Chem.
278
36115-36127
2003
Homo sapiens (Q9NPF2), Homo sapiens (Q9NRB3), Homo sapiens (Q8NET6), Homo sapiens
brenda
Yamada, T.; Ohtake, S.; Sato, M.; Habuchi, O.
Chondroitin 4-sulphotransferase-1 and chondroitin 6-sulphotransferase-1 are affected differently by uronic acid residues neighbouring the acceptor GalNAc residues
Biochem. J.
384
567-575
2004
Homo sapiens
brenda
Yusa, A.; Kitajima, K.; Habuchi, O.
N-linked oligosaccharides are required to produce and stabilize the active form of chondroitin 4-sulphotransferase-1
Biochem. J.
388
115-121
2005
Rattus norvegicus
brenda
Kluppel, M.; Wight, T.N.; Chan, C.; Hinek, A.; Wrana, J.L.
Maintenance of chondroitin sulfation balance by chondroitin-4-sulfotransferase 1 is required for chondrocyte development and growth factor signaling during cartilage morphogenesis
Development
132
3989-4003
2005
Mus musculus
brenda
Schmidt, H.H.; Dyomin, V.G.; Palanisamy, N.; Itoyama, T.; Nanjangud, G.; Pirc-Danoewinata, H.; Haas, O.A.; Chaganti, R.S.
Deregulation of the carbohydrate (chondroitin 4) sulfotransferase 11 (CHST11) gene in a B-cell chronic lymphocytic leukemia with a t(12;14)(q23;q32)
Oncogene
23
6991-6996
2004
Homo sapiens
brenda
Mitsunaga, C.; Mikami, T.; Mizumoto, S.; Fukuda, J.; Sugahara, K.
Chondroitin sulfate/dermatan sulfate hybrid chains in the development of cerebellum. Spatiotemporal regulation of the expression of critical disulfated disaccharides by specific sulfotransferases
J. Biol. Chem.
281
18942-18952
2006
Sus scrofa
brenda
Uyama, T.; Ishida, M.; Izumikawa, T.; Trybala, E.; Tufaro, F.; Bergstroem, T.; Sugahara, K.; Kitagawa, H.
Chondroitin 4-O-sulfotransferase-1 regulates E disaccharide expression of chondroitin sulfate required for Herpes simplex virus infectivity
J. Biol. Chem.
281
38668-38674
2006
Mus musculus
brenda
Ohtake, S.; Kondo, S.; Morisaki, T.; Matsumura, K.; Kimata, K.; Habuchi, O.
Expression of sulfotransferases involved in the biosynthesis of chondroitin sulfate E in the bone marrow derived mast cells
Biochim. Biophys. Acta
1780
687-695
2008
Mus musculus (Q9JME2), Mus musculus
brenda
Akita, K.; von Holst, A.; Furukawa, Y.; Mikami, T.; Sugahara, K.; Faissner, A.
Expression of multiple chondroitin/dermatan sulfotransferases in the neurogenic regions of the embryonic and adult central nervous system implies that complex chondroitin sulfates have a role in neural stem cell maintenance
Stem Cells
26
798-809
2008
Mus musculus (Q9JME2), Mus musculus
brenda
Mizumoto, S.; Mikami, T.; Yasunaga, D.; Kobayashi, N.; Yamauchi, H.; Miyake, A.; Itoh, N.; Kitagawa, H.; Sugahara, K.
Chondroitin 4-O-sulfotransferase-1 is required for somitic muscle development and motor axon guidance in zebrafish
Biochem. J.
419
387-399
2009
Danio rerio (Q7T3S3), Danio rerio (Q75W66), Danio rerio
brenda
Duelli, A.; Roennberg, E.; Waern, I.; Ringvall, M.; Kolset, S.O.; Pejler, G.
Mast cell differentiation and activation is closely linked to expression of genes coding for the serglycin proteoglycan core protein and a distinct set of chondroitin sulfate and heparin sulfotransferases
J. Immunol.
183
7073-7083
2009
Mus musculus, Mus musculus C57BL/6
brenda
Izumikawa, T.; Okuura, Y.; Koike, T.; Sakoda, N.; Kitagawa, H.
Chondroitin 4-O-sulfotransferase-1 regulates the chain length of chondroitin sulfate in co-operation with chondroitin N-acetylgalactosaminyltransferase-2
Biochem. J.
434
321-331
2011
Mus musculus
brenda
Izumikawa, T.; Koike, T.; Kitagawa, H.
Chondroitin 4-O-sulfotransferase-2 regulates the number of chondroitin sulfate chains initiated by chondroitin N-acetylgalactosaminyltransferase-1
Biochem. J.
441
697-705
2012
Mus musculus
brenda
Mizumoto, S.; Watanabe, M.; Yamada, S.; Sugahara, K.
Expression of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase involved in chondroitin sulfate synthesis is responsible for pulmonary metastasis
BioMed Res. Int.
2013
656319
2013
Mus musculus (Q9JME2)
brenda
Nadanaka, S.; Kinouchi, H.; Kitagawa, H.
Histone deacetylase-mediated regulation of chondroitin 4-O-sulfotransferase-1 (Chst11) gene expression by Wnt/beta-catenin signaling
Biochem. Biophys. Res. Commun.
480
234-240
2016
Mus musculus (Q9JME2)
brenda
Bhattacharyya, S.; Feferman, L.; Tobacman, J.K.
Regulation of chondroitin-4-sulfotransferase (CHST11) expression by opposing effects of arylsulfatase B on BMP4 and Wnt9A
Biochim. Biophys. Acta
1849
342-352
2015
Homo sapiens (Q9NPF2), Homo sapiens, Mus musculus (Q9JME2)
brenda
Izumikawa, T.; Dejima, K.; Watamoto, Y.; Nomura, K.H.; Kanaki, N.; Rikitake, M.; Tou, M.; Murata, D.; Yanagita, E.; Kano, A.; Mitani, S.; Nomura, K.; Kitagawa, H.
Chondroitin 4-O-sulfotransferase is indispensable for sulfation of chondroitin and plays an important role in maintaining normal life span and oxidative stress responses in nematodes
J. Biol. Chem.
291
23294-23304
2016
Caenorhabditis elegans (Q09272), Caenorhabditis elegans, Caenorhabditis elegans N2 (Q09272)
brenda
Bhattacharyya, S.; Zhang, X.; Feferman, L.; Johnson, D.; Tortella, F.C.; Guizzetti, M.; Tobacman, J.K.
Decline in arylsulfatase B and increase in chondroitin 4-sulfotransferase combine to increase chondroitin 4-sulfate in traumatic brain injury
J. Neurochem.
134
728-739
2015
Rattus norvegicus (P69478)
brenda
Dierker, T.; Shao, C.; Haitina, T.; Zaia, J.; Hinas, A.; Kjellen, L.
Nematodes join the family of chondroitin sulfate-synthesizing organisms: Identification of an active chondroitin sulfotransferase in Caenorhabditis elegans
Sci. Rep.
6
34662
2016
Caenorhabditis elegans (Q09272), Caenorhabditis elegans, Caenorhabditis elegans N2 (Q09272)
brenda
Oliveira-Ferrer, L.; Hessling, A.; Trillsch, F.; Mahner, S.; Milde-Langosch, K.
Prognostic impact of chondroitin-4-sulfotransferase CHST11 in ovarian cancer
Tumour Biol.
36
9023-9030
2015
Homo sapiens (Q9NPF2), Homo sapiens
brenda
He, W.; Zhu, Y.; Shirke, A.; Sun, X.; Liu, J.; Gross, R.A.; Koffas, M.A.G.; Linhardt, R.J.; Li, M.
Expression of chondroitin-4-O-sulfotransferase in Escherichia coli and Pichia pastoris
Appl. Microbiol. Biotechnol.
101
6919-6928
2017
Homo sapiens (Q9NPF2), Homo sapiens
brenda
Yamaguchi, K.; Asakura, K.; Imamura, M.; Kawai, G.; Sakamoto, T.; Furihata, T.; Linhardt, R.J.; Igarashi, K.; Toida, T.; Higashi, K.
Polyamines stimulate the CHSY1 synthesis through the unfolding of the RNA G-quadruplex at the 5-untraslated region
Biochem. J.
475
3797-3812
2018
Homo sapiens (Q9NRB3)
brenda
Zhou, Z.; Li, Q.; Huang, H.; Wang, H.; Wang, Y.; Du, G.; Chen, J.; Kang, Z.
A microbial-enzymatic strategy for producing chondroitin sulfate glycosaminoglycans
Biotechnol. Bioeng.
115
1561-1570
2018
Rattus norvegicus (P69478)
brenda
Pan, H.; Xue, W.; Zhao, W.; Schachner, M.
Expression and function of chondroitin 4-sulfate and chondroitin 6-sulfate in human glioma
FASEB J.
34
2853-2868
2020
Homo sapiens (Q9NPF2), Homo sapiens
brenda
Ramachandra, R.; Namburi, R.B.; Dupont, S.T.; Ortega-Martinez, O.; van Kuppevelt, T.H.; Lindahl, U.; Spillmann, D.
A potential role for chondroitin sulfate/dermatan sulfate in arm regeneration in Amphiura filiformis
Glycobiology
27
438-449
2017
Amphiura filiformis
brenda
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