Activating Compound | Comment | Organism | Structure |
---|---|---|---|
additional information | glycosylation is not required for substrate Wnt3a palmitoylation, which is necessary but not sufficient for Wnt3a secretion | Homo sapiens | |
additional information | glycosylation is not required for substrate Wnt3a palmitoylation, which is necessary but not sufficient for Wnt3a secretion | Mus musculus |
Protein Variants | Comment | Organism |
---|---|---|
C187A | site-directed mutagenesis, increase in Wnt signaling activity of about 1.5fold upon expression of PORCNC187A compared to wild-type PORCN | Homo sapiens |
C375X | site-directed mutagenesis, mutations introduced in PORCN at either Cys375, Cys381 or Cys385, all situated on a predicted luminal loop projecting from transmembrane domain VII that contains the catalytic His341 residue, have detrimental effects on Wnt3a palmitoylation and signaling that are comparable to that of the catalytically dead H341A mutant | Homo sapiens |
C381X | site-directed mutagenesis, mutations introduced in PORCN at either Cys375, Cys381 or Cys385, all situated on a predicted luminal loop projecting from transmembrane domain VII that contains the catalytic His341 residue, have detrimental effects on Wnt3a palmitoylation and signaling that are comparable to that of the catalytically dead H341A mutant | Homo sapiens |
C385X | site-directed mutagenesis, mutations introduced in PORCN at either Cys375, Cys381 or Cys385, all situated on a predicted luminal loop projecting from transmembrane domain VII that contains the catalytic His341 residue, have detrimental effects on Wnt3a palmitoylation and signaling that are comparable to that of the catalytically dead H341A mutant | Homo sapiens |
H341A | site-directed mutagenesis, catalytically inactive mutant | Homo sapiens |
H341A | site-directed mutagenesis, the mutation reduces Wnt signaling relative to wild-type PORCN | Homo sapiens |
additional information | the cysteine mutations might be detrimental to the enzyme's tertiary structure and its catalytic activity | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
endoplasmic reticulum membrane | integral membrane protein | Homo sapiens | 5789 | - |
endoplasmic reticulum membrane | integral membrane protein | Mus musculus | 5789 | - |
additional information | palmitoylated Wnt3a proteins are found throughout the cytosol and at the plasma membrane but not in the nucleus | Homo sapiens | - |
- |
additional information | palmitoylated Wnt3a proteins are found throughout the cytosol and at the plasma membrane but not in the nucleus | Mus musculus | - |
- |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
(9Z)-hexadec-9-enoyl-CoA + [Wnt3a]-L-serine | Homo sapiens | Wnt3a is palmitoylated in the endoplasmic reticulum and targeted to exosomes, palmitoylated Wnt3a proteins are found throughout the cytosol and at the plasma membrane but not in the nucleus, overview | CoA + [Wnt3a]-O-(9Z)-hexadec-9-enoyl-L-serine | - |
? | |
(9Z)-hexadec-9-enoyl-CoA + [Wnt3a]-L-serine | Mus musculus | Wnt3a is palmitoylated in the endoplasmic reticulum and targeted to exosomes, palmitoylated Wnt3a proteins are found throughout the cytosol and at the plasma membrane but not in the nucleus, overview | CoA + [Wnt3a]-O-(9Z)-hexadec-9-enoyl-L-serine | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q9H237 | - |
- |
Mus musculus | Q9JJJ7 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
lipoprotein | primate-specific S-palmitoylation of PORCN at Cys187, fatty acylation of PORCN is not due to autopalmitoylation. The palmitoylation of the enzyme, a membrane-bound O-acyltransferase or MBOAT protein, partially regulates Wnt palmitoylation and signaling, overview. Loss of palmitoylation of PORCN results in a modest increase in Wnt signaling, suggesting a negative regulatory role for PORCN Cys187 fatty acylation | Homo sapiens |
lipoprotein | the enzyme itself is palmitoylated, the palmitoylation of the membrane-bound O-acyltransferase, MBOAT protein, partially regulates Wnt palmitoylation and signaling, overview | Mus musculus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
fibroblast | - |
Mus musculus | - |
HEK-293 cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
(9Z)-hexadec-9-enoyl-CoA + [Wnt3a]-L-serine | Wnt3a is palmitoylated in the endoplasmic reticulum and targeted to exosomes, palmitoylated Wnt3a proteins are found throughout the cytosol and at the plasma membrane but not in the nucleus, overview | Homo sapiens | CoA + [Wnt3a]-O-(9Z)-hexadec-9-enoyl-L-serine | - |
? | |
(9Z)-hexadec-9-enoyl-CoA + [Wnt3a]-L-serine | Wnt3a is palmitoylated in the endoplasmic reticulum and targeted to exosomes, palmitoylated Wnt3a proteins are found throughout the cytosol and at the plasma membrane but not in the nucleus, overview | Mus musculus | CoA + [Wnt3a]-O-(9Z)-hexadec-9-enoyl-L-serine | - |
? | |
(9Z)-hexadec-9-enoyl-CoA + [Wnt3a]-L-serine | Wnt3a is palmitoylated by fatty acids 13-16 carbons in length at Ser209 but not at Cys77, consistent with a slow turnover rate, glycosylation is not required for Wnt3a palmitoylation, which is necessary but not sufficient for Wnt3a secretion | Homo sapiens | CoA + [Wnt3a]-O-(9Z)-hexadec-9-enoyl-L-serine | - |
? | |
(9Z)-hexadec-9-enoyl-CoA + [Wnt3a]-L-serine | Wnt3a is palmitoylated by fatty acids 13-16 carbons in length at Ser209 but not at Cys77, consistent with a slow turnover rate, glycosylation is not required for Wnt3a palmitoylation, which is necessary but not sufficient for Wnt3a secretion | Mus musculus | CoA + [Wnt3a]-O-(9Z)-hexadec-9-enoyl-L-serine | - |
? | |
additional information | no activity with palmitoylation-defective Wnt3aS209A mutant | Homo sapiens | ? | - |
? | |
additional information | no activity with palmitoylation-defective Wnt3aS209A mutant | Mus musculus | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
PORCN | - |
Homo sapiens |
PORCN | - |
Mus musculus |
General Information | Comment | Organism |
---|---|---|
evolution | the enzyme belongs to the membrane-bound O-acyltransferase family | Homo sapiens |
evolution | the enzyme belongs to the membrane-bound O-acyltransferase family | Mus musculus |
physiological function | the enzyme is critical for Wnt acylation and maintaining its hydrophobic nature, palmitoylation of the enzyme protein itself partially regulates Wnt palmitoylation and signaling, loss of palmitoylation of PORCN results in a modest increase in Wnt signaling, suggesting a negative regulatory role for PORCN Cys187 fatty acylation. Overexpression of PORCN promoted glycan processing of wild-type Wnt3a and the Ser209 (and Cys77) mutant, suggesting an additional acylation-independent role for the enzyme PORCN in maturation of Wnt3a | Homo sapiens |
physiological function | the enzyme is critical for Wnt acylation and maintaining its hydrophobic nature, palmitoylation of the enzyme protein itself partially regulates Wnt palmitoylation and signaling. Overexpression of PORCN promoted glycan processing of wild-type Wnt3a and the Ser209 (and Cys77) mutant, suggesting an additional acylation-independent role for the enzyme PORCN in maturation of Wnt3a | Mus musculus |