{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZDHHC2 is a member of the DHHC family of palmitoyl acyltransferases that catalyze the covalent attachment of palmitate to select cysteine residues on target proteins. This post‐translational modification regulates protein trafficking, stability, membrane association, and functional interactions. Several studies have demonstrated that ZDHHC2 can specifically modify substrates such as CKAP4, tetraspanins (e.g., CD9 and CD151), and other signaling proteins. In particular, palmitoylation of CKAP4 by ZDHHC2 not only directs its proper subcellular localization from the endoplasmic reticulum to the plasma membrane and even the nucleus, but also mediates its tumor suppressor function and influence on cellular proliferation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its enzymatic activity, ZDHHC2 displays dynamic subcellular localization, cycling among the plasma membrane, recycling endosomes, and other vesicular compartments. In neurons, ZDHHC2 regulates the palmitoylation and membrane recruitment of key synaptic proteins such as PSD95 and the R7BP complex, which in turn modulate G protein–coupled signaling. Moreover, in T cells, ZDHHC2 has been shown to palmitoylate the tyrosine kinase Lck, thereby influencing its membrane association and function in T cell activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, diminished expression or loss of function of ZDHHC2 has been linked to tumorigenesis and metastasis in various cancers, including hepatocellular carcinoma and gastric adenocarcinoma. Functional studies indicate that reduced ZDHHC2 expression is associated with early metastatic recurrence, increased tumor size, and enhanced invasive properties, supporting its role as a tumor suppressor. In addition, emerging evidence from models of psoriasis has revealed that ZDHHC2 is critical for regulating inflammatory responses by modulating interferon‐α production in plasmacytoid dendritic cells, while genetic associations point to its involvement in neuropsychiatric conditions such as schizophrenia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jun Zhang, Sonia L Planey, Carolina Ceballos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of CKAP4/p63 as a major substrate of the palmitoyl acyltransferase DHHC2, a putative tumor suppressor, using a novel proteomics method."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M800069-MCP200"}], "href": "https://doi.org/10.1074/mcp.M800069-MCP200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18296695"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18296695"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chandan Sharma, Xiuwei H Yang, Martin E Hemler "}, {"type": "b", "children": [{"type": "t", "text": "DHHC2 affects palmitoylation, stability, and functions of tetraspanins CD9 and CD151."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e07-11-1164"}], "href": "https://doi.org/10.1091/mbc.e07-11-1164"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18508921"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18508921"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sonia L Planey, Susan K Keay, Chen-Ou Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Palmitoylation of cytoskeleton associated protein 4 by DHHC2 regulates antiproliferative factor-mediated signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e08-08-0849"}], "href": "https://doi.org/10.1091/mbc.e08-08-0849"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19144824"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19144824"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lixia Jia, Maurine E Linder, Kendall J Blumer "}, {"type": "b", "children": [{"type": "t", "text": "Gi/o signaling and the palmitoyltransferase DHHC2 regulate palmitate cycling and shuttling of RGS7 family-binding protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.193763"}], "href": "https://doi.org/10.1074/jbc.M110.193763"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21343290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21343290"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jennifer Greaves, Juliet A Carmichael, Luke H Chamberlain "}, {"type": "b", "children": [{"type": "t", "text": "The palmitoyl transferase DHHC2 targets a dynamic membrane cycling pathway: regulation by a C-terminal domain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E10-11-0924"}], "href": "https://doi.org/10.1091/mbc.E10-11-0924"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21471008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21471008"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ruth Zeidman, Gemma Buckland, Marek Cebecauer, et al. 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