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Literature summary for 2.4.1.B72 extracted from
- Distinct C-mannosylation of netrin receptor thrombospondin type 1 repeats by mammalian DPY19L1 and DPY19L3 (2017), Proc. Natl. Acad. Sci. USA, 114, 2574-2579 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene dpy19, recombinant enzyme expression in Drosophila melanogaster S2 cells | Caenorhabditis elegans |
| gene Dpy19l1, using CRISPR-Cas9 mutagenesis, Chinese hamster ovary (CHO) single knockout cells are generated as well as a triple knockout lacking DPY19L1, -L3, and -L4, and the respective mouse enzymes are reintroduced in the cells. Transient expression of C-terminal V5-tagged UNC5A in CHO cell single knockouts of DPY19L1, -L3, and -L4. Overexpression of DPY19L1 results in detection of TSR1 peptides with a maximum of two C-mannoses | Mus musculus |
| gene Dpy19l3, using CRISPR-Cas9 mutagenesis, Chinese hamster ovary (CHO) single knockout cells are generated as well as a triple knockout lacking DPY19L1, -L3, and -L4, and the respective mouse enzymes are reintroduced in the cells. Transient expression of C-terminal V5-tagged UNC5A in CHO cell single knockouts of DPY19L1, -L3, and -L4. The ratio of this C-mannosylated peptide to the nonmannosylated peptide is higher in cells overexpressing DPY19L3 than in wild-type cells | Mus musculus |
| gene Dpy19l4, using CRISPR-Cas9 mutagenesis, Chinese hamster ovary (CHO) single knockout cells are generated as well as a triple knockout lacking DPY19L1, -L3, and -L4, and the respective mouse enzymes are reintroduced in the cells. Transient expression of C-terminal V5-tagged UNC5A in CHO cell single knockouts of DPY19L1, -L3, and -L4 | Mus musculus |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | Caenorhabditis elegans | C-mannosylation is initially described as a modification of the first tryptophan in the WxxW consensus sequence, but is also observed on tryptophans that are not part of this motif. In addition to WxxW, WxxC is also considered to be a consensus sequence for C-mannosylation | ? | - |
- |
 |
| additional information | Mus musculus | mammalian C-mannosyltransferases DPY19L1 and DPY19L3 do not have a dual WxxW/C recognition motif, but are active C-mannosyltransferases with distinct substrate specificities | ? | - |
- |
|
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Caenorhabditis elegans | P34413 | - |
- |
| Mus musculus | A2AJQ3 | - |
- |
| Mus musculus | A6X919 | - |
- |
| Mus musculus | Q71B07 | - |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| additional information | C-mannosylation is initially described as a modification of the first tryptophan in the WxxW consensus sequence, but is also observed on tryptophans that are not part of this motif. In addition to WxxW, WxxC is also considered to be a consensus sequence for C-mannosylation | Caenorhabditis elegans | ? | - |
- |
|
| additional information | mammalian C-mannosyltransferases DPY19L1 and DPY19L3 do not have a dual WxxW/C recognition motif, but are active C-mannosyltransferases with distinct substrate specificities | Mus musculus | ? | - |
- |
|
| additional information | no activity by DPY19L4 isozyme on murine UNC5A | Mus musculus | ? | - |
- |
|
| additional information | the single Caenorhabditis elegans C-mannosyltransferase DPY-19 mannosylates the first two tryptophans of a WxxWxxW motif | Caenorhabditis elegans | ? | - |
- |
|
| UNC5A + GDP-mannose | C-mannosylation of murine UNC5A | Caenorhabditis elegans | C-mannosyl-UNC5A + GDP | - |
? | |
| UNC5A + GDP-mannose | C-mannosylation of murine UNC5A, DPY19L1 can C-mannosylate the first two tryptophans in the WxxWxxWxxC sequence of UNC5A TSRs | Mus musculus | C-mannosyl-UNC5A + GDP | - |
? | |
| UNC5A + GDP-mannose | C-mannosylation of murine UNC5A, DPY19L3 mannosylates the third tryptophan of this sequence and might require a WxxC motif | Mus musculus | C-mannosyl-UNC5A + GDP | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| dpy19 | - |
Caenorhabditis elegans |
| DPY19L1 | - |
Mus musculus |
| DPY19L3 | - |
Mus musculus |
| DPY19L4 | - |
Mus musculus |
| dumpy-19 | - |
Caenorhabditis elegans |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | isozyme DPY19L1 activity is conserved in mammals and Caenorhabditis elegans, whereas DPY19L3 has acquired another activity, mannosylation of W3 of the WxxWxxWxxC motif in TSRs. DPY19L1 and DPY19L3 act on the first two and the third tryptophan, respectively | Mus musculus |
| malfunction | inactivation of DPY19L1 but not DPY19L3 strongly reduces the secretion of UNC5A TSRs and leads to the accumulation of the membrane bound protein in the endoplasmmic reticulum | Mus musculus |
| physiological function | mannosylation by DPY19L1 but not DPY19L3 is required for transport of UNC5A from the endoplasmic reticulum to the cell surface. The importance of C-mannosylation for protein secretion might reflect a function in protein folding | Mus musculus |
| physiological function | the importance of C-mannosylation for protein secretion might reflect a function in protein folding | Caenorhabditis elegans |
| physiological function | the importance of C-mannosylation for protein secretion might reflect a function in protein folding | Mus musculus |
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