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Information on EC 2.8.2.35 - dermatan 4-sulfotransferase and Organism(s) Homo sapiens
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2.8.2.35 dermatan 4-sulfotransferaseIUBMB Comments
The sulfation takes place at the 4-position of N-acetyl-D-galactosamine residues of dermatan. D4ST-1 shows a strong preference in vitro for sulfate transfer to IdoUAalpha(1,3)GalNAcbeta(1,4) that is flanked by GlcUAbeta(1,3)GalNAcbeta(1,4) as compared with IdoUAalpha(1,3)GalNAcbeta(1,4) flanked by IdoUAalpha(1,3)GalNAcbeta(1,4) .
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Word Map
- 2.8.2.35
- ehlers-danlos
- chondroitin
-
musculocontractural
-
hyperextensibility
-
fragility-related
- contractures
- decorin
-
iduronic
-
thumb-clubfoot
-
4-o-sulfation
-
kyphoscoliosis
-
mceds
-
hypermobility
-
bruisable
-
uronyl
- talipes
-
hypermobl
-
2-o-sulfotransferase
-
idoua
-
4-sulfate
-
bruisability
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
chst14, d4st-1, dermatan 4-o-sulfotransferase-1, d4st1, dermatan 4-o-sulfotransferase 1, chst14/d4st1, dermatan 4-o-sulfotransferase, carbohydrate sulfotransferase 14, n-acetylgalactosamine 4-o-sulfotransferase 1, dermatan-4-sulfotransferase-1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CHST14
D4ST1
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
3'-phospho-5'-adenylyl sulfate:[dermatan]-N-acetyl-D-galactosamine 4-sulfotransferase
The sulfation takes place at the 4-position of N-acetyl-D-galactosamine residues of dermatan. D4ST-1 shows a strong preference in vitro for sulfate transfer to IdoUAalpha(1,3)GalNAcbeta(1,4) that is flanked by GlcUAbeta(1,3)GalNAcbeta(1,4) as compared with IdoUAalpha(1,3)GalNAcbeta(1,4) flanked by IdoUAalpha(1,3)GalNAcbeta(1,4) [1].
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetyl-D-galactosamine
adenosine 3',5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetyl-D-galactosamine
-
-
-
?
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetylgalactosamine
adenosine 3'-5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetylgalactosamine
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetylgalactosamine
adenosine 3'-5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetylgalactosamine
-
-
-
?
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetylgalactosamine
adenosine 3'-5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetylgalactosamine
-
-
-
-
?
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetylgalactosamine
adenosine 3'-5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetylgalactosamine
dermatan 4-O-sulfotransferase 1 is pivotal in the formation of iduronic acid blocks in dermatan sulfate
-
-
?
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetylgalactosamine
adenosine 3'-5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetylgalactosamine
desulfated dermatan sulfate from porcine intestine. The sulfation takes place at the 4-position of N-acetylgalactosamine residues of dermatan. D4ST-1 transfers sulfate to the C-4 hydroxyl of (1,4)-linked GalNAc that is substituted with an alpha-linked iduronic acid at the C-3 hydroxyl. D4ST-1 shows a strong preference in vitro for sulfate transfer to IdoUAalpha(1,3)GalNAcbeta(1,4) that is flanked by GlcUAbeta(1,3)GalNAcbeta(1,4) as compared with IdoUAalpha(1,3)GalNAcbeta(1,4) flanked by IdoUAalpha1,3GalNAcbeta1,4. The specificity of D4ST-1 when assayed in vitro suggests that the addition of sulfate to GalNAc occurs immediately after epimerization of GlcUA to IdoUA. While D4ST-1 is able to transfer sulfate to both dermatan and chondroitin, the rate of transfer is nearly 10fold greater to dermatan than to chondroitin when the same substrate concentrations are used. D4ST-1 only displays a significant transfer of sulfate to chondroitin at relatively high substrate concentrations, raising the possibility that the chondroitin is contaminated with small amounts of dermatan and/or that occasional iduronic acid residues are present in the chondroitin and utilized by the D4ST-1
-
-
?
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetylgalactosamine
adenosine 3'-5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetylgalactosamine
most efficiently utilizes GalNAc residues located not only in the sequence -IdoUA-GalNAc-IdoUA- but also in -GlcUA-Gal-NAc-IdoUA- and -IdoUA-GalNAc-GlcUA-. The isolated oligosaccharide structures suggest that 4-O-sulfation promotes subsequent 4-O-sulfation of GalNAc in the neighboring disaccharide unit
-
-
?
additional information
?
-
-
the enzyme catalyzes the 4-O-sulfation of N-acetylgalactosamine in the repeating iduronic acid-alpha-1,3-N-acetylgalactosamine disaccharide sequence to form dermatan sulfate
-
-
?
additional information
?
-
dermatan sulfate epimerase 1 and dermatan 4-O-sulfotransferase 1 form complexes that generate long epimerized 4-O-sulfated blocks
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetyl-D-galactosamine
adenosine 3',5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetyl-D-galactosamine
-
-
-
?
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetylgalactosamine
adenosine 3'-5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetylgalactosamine
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetylgalactosamine
adenosine 3'-5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetylgalactosamine
-
-
-
?
3'-phospho-5'-adenylyl sulfate + [dermatan]-N-acetylgalactosamine
adenosine 3'-5'-bisphosphate + [dermatan]-4-O-sulfo-N-acetylgalactosamine
-
-
-
-
?
additional information
?
-
-
the enzyme catalyzes the 4-O-sulfation of N-acetylgalactosamine in the repeating iduronic acid-alpha-1,3-N-acetylgalactosamine disaccharide sequence to form dermatan sulfate
-
-
?
additional information
?
-
dermatan sulfate epimerase 1 and dermatan 4-O-sulfotransferase 1 form complexes that generate long epimerized 4-O-sulfated blocks
-
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.8
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
no change in activity in dermatan 4-O sulfotransferase is observed, and only a minor decrease in dermatan 4-O-sulfotransferase-1 (D4ST-1) mRNA is observed after treatment with with transforming growth factor-beta (TGF-beta)
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
co-localization with dermatan sulfate epimerase 1 (DS-epi1)
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
During the biosynthesis of chondroitin/dermatan sulfate (CS/DS), a variable fraction of glucuronic acid is converted to iduronic acid through the activities of two epimerases, dermatan sulfate epimerases 1 (DS-epi1) and 2 (DS-epi2). Without association with other enzymes, DS-epi1 activity produces structures that have only a few adjacent iduronic acid units. In vivo, concomitant with epimerization, dermatan 4-O-sulfotransferase 1 (D4ST1) sulfates the GalNAc adjacent to iduronic acid. This sulfation facilitates DSepi1 activity and enables the formation of long blocks of sulfated iduronic acid-containing domains, which can be major components of CS/DS. Concerted action of DS-epi1 and D4ST1. D4ST1 directly interacts with DS-epi1, but not with DS-epi2. The iduronic acid-forming enzymes operate in complexes, similar to other enzymes active in glycosaminoglycan biosynthesis. siRNA-mediated reduction of DS-epi2 in MCF 10a cells results in a marked reduction of the two epimerases and IdoA biosynthesis
physiological function
D4ST-1 is indispensable in the formation of the important functional domains composed of alternating iduronic acid and 4-O-sulfated N-acetylgalactosamine residues (named 4-O-sulfated iduronic acid blocks) in dermatan sulfate and cannot be compensated by other 4-O-sulfotransferases
malfunction
adducted thumb-clubfoot syndrome is genetically homogeneous and is caused by loss-of-function mutations in CHST14 leading to a deficiency of sulfated dermatan in affected tissues
malfunction
-
adducted thumb-clubfoot syndrome is caused by homozygous nonsense and missense mutations in CHST14 which encodes N-acetylgalactosamine 4-O-sulfotransferase 1 leading to congenital malformations, contractures of thumbs and feet, and a typical facial appearance
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). CHSTE_HUMAN
376
0
42997
Swiss-Prot
Mitochondrion (Reliability: 2)
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene D4ST1, quantitative RT-PCR enzyme expression analysis, overexpression of enzyme D4ST1 in COS-7 cells, co-expression with dermatan sulfate epimerases DS-epi1 and DS-epi2
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
downregulation of D4ST-1 in primary human lung fibroblasts leads to a drastic specific reduction of iduronic acid blocks. No change of epimerase activity is found, indicating that the influence of D4ST-1 on epimerization is not due to an altered expression level of the DS-epimerases. Analysis of the dermatan sulfate chains shows that D4ST-1 is essential for the biosynthesis of the disulfated structure iduronic acid-2-O-sulfate-N-acetylgalactosamine-4-O-sulfate, thus confirmed to be strictly connected with the iduronic acid blocks. Also the biologically important residue hexuronic acid-N-acetylgalactosamine-4,6-O-disulfate considerably decreases after D4ST-1 downregulation
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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 (Q8NCH0), Homo sapiens
Tiedemann, K.; Olander, B.; Eklund, E.; Todorova, L.; Bengtsson, M.; Maccarana, M.; Westergren-Thorsson, G.; Malmstroem, A.
Regulation of the chondroitin/dermatan fine structure by transforming growth factor-b1 through effects on polymer-modifying enzymes
Glycobiology
15
1277-1285
2005
Homo sapiens (Q8NCH0), Homo sapiens
Dndar, M.; Mller, T.; Zhang, Q.; Pan, J.; Steinmann, B.; Vodopiutz, J.; Gruber, R.; Sonoda, T.; Krabichler, B.; Utermann, G.; Baenziger, J.U.; Zhang, L.; Janecke, A.R.
Loss of dermatan-4-sulfotransferase 1 function results in adducted thumb-clubfoot syndrome
Am. J. Hum. Genet.
85
873-882
2009
Homo sapiens (Q8NCH0), Homo sapiens
Pacheco, B.; Maccarana, M.; Malmstrm, A.
Dermatan 4-O-sulfotransferase 1 is pivotal in the formation of iduronic acid blocks in dermatan sulfate
Glycobiology
19
1197-1203
2009
Homo sapiens (Q8NCH0), Homo sapiens
Evers, M.R.; Xia, G.; Kang, H.G.; Schachner, M.; Baenziger, J.U.
Molecular cloning and characterization of a dermatan-specific N-acetylgalactosamine 4-O-sulfotransferase
J. Biol. Chem.
276
36344-36353
2001
Homo sapiens (Q8NCH0), Homo sapiens
Zhang, L.; Mueller, T.; Baenziger, J.U.; Janecke, A.R.
Congenital disorders of glycosylation with emphasis on loss of dermatan-4-sulfotransferase
Prog. Mol. Biol. Transl. Sci.
93
289-307
2010
Homo sapiens
Tykesson, E.; Hassinen, A.; Zielinska, K.; Thelin, M.A.; Frati, G.; Ellervik, U.; Westergren-Thorsson, G.; Malmstroem, A.; Kellokumpu, S.; Maccarana, M.
Dermatan sulfate epimerase 1 and dermatan 4-O-sulfotransferase 1 form complexes that generate long epimerized 4-O-sulfated blocks
J. Biol. Chem.
293
13725-13735
2018
Homo sapiens (Q8NCH0)
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