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Literature summary for 2.8.2.8 extracted from
- ''Coding'' and ''Decoding'' hypothesis for the regulatory mechanism involved in heparan sulfate biosynthesis (2016), Carbohydr. Res., 428, 1-7 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene NDST1, recombinant expression in yeast cells, recombinant overexpression of NDST1 in HEK-293 cells | Homo sapiens |
| recombinant overexpression of NDST2 in HEK-293 cells | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | overexpression of NDST1 or NDST2 in recombinant human embryonic kidney 293 cells gives rise to different heparan sulfate (HS) N-sulfation patterns. The HS produced in cells transfected with NDST1 and NDST2 typically shows increased levels of N-sulfation. However, compared with cells overexpressing NDST1, the HS generated by cells overexpressing NDST2 has longer N-sulfation regions and a higher degree of N-sulfation | Homo sapiens |
| additional information | overexpression of NDST1 or NDST2 in recombinant human embryonic kidney 293 cells gives rise to different heparan sulfate (HS) N-sulfation patterns. The HS produced in cells transfected with NDST1 and NDST2 typically shows increased levels of N-sulfation. However, compared with cells overexpressing NDST1, the HS generated by cells overexpressing NDST2 has longer N-sulfation regions and a higher degree of N-sulfation. Furthermore, the transfection of NDST-deficient COS cells with NDST1 results in the formation of HS with a high affinity for FGF. In contrast, the overexpression of NDST1 in wild-type COS cells has very little effect on the N-acetylation to N-sulfation ratio of HS | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| Golgi apparatus | - |
Homo sapiens | 5794 | - |
| membrane | NDST isozymes are all type II membrane proteins. They have a short cytoplasmic tail (12 to 18 amino acids), transmembrane and stem regions consisting of about 40 amino acids and a catalytic domain responsible for their independent N-deacetylation and N-sulfation activities | Homo sapiens | 16020 | - |
| membrane | NDST isozymes are all type II membrane proteins. They have have a short cytoplasmic tail (12 to 18 amino acids), transmembrane and stem regions consisting of about 40 amino acids and a catalytic domain responsible for their independent N-deacetylation and N-sulfation activities | Homo sapiens | 16020 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine | Homo sapiens | - |
adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine | - |
? |  |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | O95803 | - |
- |
| Homo sapiens | P52848 | - |
- |
| Homo sapiens | P52849 | - |
- |
| Homo sapiens | Q9H3R1 | - |
- |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| 3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine = adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine | comparison of catalytic mechanism aspects of the NDST isozymes, overview | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | - |
Homo sapiens | - |
| brain | low level in adult brain tissue | Homo sapiens | - |
| embryo | predominantly | Homo sapiens | - |
| heart | - |
Homo sapiens | - |
| additional information | NDST3 and NDST4 are predominantly expressed during embryonic development, although NDST3 is also found in adult heart and brain tissues, whereas NDST4 is only present at low levels in adult brain tissue | Homo sapiens | - |
| additional information | the mRNAs of NDST1 and NDST2 are transcribed in all embryonic and adult tissues, but at different levels during the different stages of development, as well as different organs. NDST1 is widely distributed in the body | Homo sapiens | - |
| additional information | the mRNAs of NDST1 and NDST2 are transcribed in all embryonic and adult tissues, but at different levels during the different stages of development, as well as different organs. NDST2 is only expressed in connective tissue-type mast cells, which produce heparin in vivo | Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 3'-phosphoadenylyl sulfate + [heparan sulfate]-glucosamine | - |
Homo sapiens | adenosine 3',5'-bisphosphate + [heparan sulfate]-N-sulfoglucosamine | - |
? | |
| additional information | the enzyme NDST removes the acetyl group from the GlcNAc residue and transfers a sulfate group to the primary amine forming a GlcNS substitute | Homo sapiens | ? | - |
- |
|
| additional information | the enzyme NDST removes the acetyl group from the GlcNAc residue and transfers a sulfate group to the primary amine forming a GlcNS substitute. Isozyme NDST3 has relatively higher N-deacetylase activity and lower sulfotransferase activity | Homo sapiens | ? | - |
- |
|
| additional information | the enzyme NDST removes the acetyl group from the GlcNAc residue and transfers a sulfate group to the primary amine forming a GlcNS substitute. Isozyme NDST4 has relatively higher sulfotransferase activity and lower N-deacetylase activity | Homo sapiens | ? | - |
- |
|
| additional information | the enzyme NDST removes the acetyl group from the GlcNAc residue and transfers a sulfate group to the primary amine forming a GlcNS substitute. The catalytic mechanism of NDST1 is responsible for determining the distribution of GlcNS residues in the heparan sulfate (HS) chains. NDST1 binds to its substrates in a random manner, but the processes catalyzed by this enzyme are nonrandom, leading to the formation of specific products in different regions of the chains. During this process, NDST1 can bind to any of the internal GlcNAc residues on the chain. Once the sulfation process has been initiated, NDST1 can then convert the GlcNAc residues to GlcNS residues in sequence from the nonreducing to the reducing end of the chain until it reaches a GlcNS residue located five units away from the reducing end. The establishment of this catalytic model for NDST1 provides direct proof that NDST1 plays a decisive role in the distribution of GlcNS residues | Homo sapiens | ? | - |
- |
|
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| N-deacetylase/N-sulfotransferase | - |
Homo sapiens |
| NDST | - |
Homo sapiens |
| Ndst1 | - |
Homo sapiens |
| NDST2 | - |
Homo sapiens |
| NDST3 | - |
Homo sapiens |
| NDST4 | - |
Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | four NDST isoforms are present in humans | Homo sapiens |
| malfunction | a complete lack of NDST1 results in an inability to synthesize HS glycan chains, which is ultimately lethal | Homo sapiens |
| physiological function | heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. But the final structure of HS chains is strictly regulated. Two major steps, namely coding and decoding steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The coding process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N-deacetylase/N-sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e. the decoding process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity. Mammalian cells can regulate the expression of the four different NDST isozymes as required during the different stages of their development and spatial orientation. In this way, the cells can make use of the different catalytic modes of activity of the NDSTs to adjust the length of the GlcNS clusters on the HS side chains, as well as the ratio of GlcNS to GlcNH2 residues | Homo sapiens |
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