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Literature summary for 2.3.1.250 extracted from

  • Gao, X.; Hannoush, R.N.
    Single-cell imaging of Wnt palmitoylation by the acyltransferase porcupine (2014), Nat. Chem. Biol., 10, 61-68.
    View publication on PubMed

Activating Compound

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

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

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/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens Q9H237
-
-
Mus musculus Q9JJJ7
-
-

Posttranslational Modification

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

Source Tissue Comment Organism Textmining
fibroblast
-
Mus musculus
-
HEK-293 cell
-
Homo sapiens
-

Substrates and Products (Substrate)

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

Synonyms Comment Organism
PORCN
-
Homo sapiens
PORCN
-
Mus musculus

General Information

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