ZDHHC6 Antibody
Description
Introduction to ZDHHC6
ZDHHC6 is an endoplasmic reticulum (ER)-localized enzyme that mediates S-acylation (palmitoylation) of transmembrane proteins, influencing their stability, trafficking, and function . It modifies substrates like calnexin, transferrin receptor, and TMPRSS2, impacting viral entry and cellular metabolism . ZDHHC6 is encoded by the ZDHHC6 gene (UniProt ID: Q9H6R6 in humans) and is implicated in cancer biology, immune regulation, and neurological processes .
Development and Validation of ZDHHC6 Antibodies
Key advancements in ZDHHC6 antibody development include:
Antibody Specificity
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Thermo Fisher’s PA5-113325: A polyclonal antibody raised against a synthetic peptide from human ZDHHC6. It detects isoform 1 (NP_060526.1) and is validated for Western blot (WB) and immunohistochemistry (IHC) in human and mouse samples .
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Cross-reactivity: Validated in CRISPR-Cas9 knockout (KO) HAP1 cells, confirming specificity through loss of signal in ZDHHC6 KO models .
Technical Validation
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Acyl-RAC Assays: Used to confirm ZDHHC6-dependent palmitoylation of substrates like calnexin and transferrin receptor .
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siRNA and KO Studies: Demonstrated reduced S-acylation of ZDHHC6 targets in KO cells, reinforcing antibody reliability .
Substrate Identification
ZDHHC6 antibodies have identified novel substrates, including:
| Substrate | Role in Biology | Citation |
|---|---|---|
| TMPRSS2 | Facilitates SARS-CoV-2 entry | |
| Bone marrow stromal antigen 2 (BST2) | Viral restriction factor | |
| Calnexin | ER chaperone | |
| Transferrin receptor (TfR) | Iron metabolism |
Disease Relevance
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Cancer: ZDHHC6 expression correlates with immune cell infiltration (e.g., CD8+ T cells, macrophages) in kidney renal clear cell carcinoma (KIRC), suggesting prognostic value .
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Neurological Disorders: ZDHHC6 activity is modulated by upstream palmitoyltransferase ZDHHC16, implicating it in ER-related pathologies .
Mechanism Studies
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Cysteine Positioning: Antibody-based assays revealed that ZDHHC6 modifies cysteines within or proximal to transmembrane domains (TMDs). Repositioning cysteines >5 residues into TMDs reduces S-acylation efficiency .
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Broad Specificity: ZDHHC6 modifies both type I (e.g., CD4) and type II (e.g., TfR) membrane proteins, highlighting its versatility .
Functional Interactions
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ZDHHC16 Dependency: ZDHHC6 activity is enhanced by ZDHHC16, forming a regulatory axis at the ER .
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Metabolic Pathways: ZDHHC6-linked S-acylation influences ribosome function and amino acid metabolism, contributing to cancer metabolic reprogramming .
Future Directions
Product Specs
Target Background
- Research has unveiled a palmitoylation cascade involving human ZDHHC6, which modifies critical endoplasmic reticulum proteins, and ZDHHC16, an upstream palmitoyltransferase. PMID: 28826475
- Knockdown of DHHC6 using shRNA in stably transfected cell lines resulted in decreased expression of the IP3R and compromised IP3R-dependent Ca(2+) flux. PMID: 25368151
- Studies have demonstrated that palmitoyl acyltransferases DHHC5, DHHC6, and DHHC8 undergo S-acylation on three cysteine residues within a novel CCX(7-13)C(S/T) motif located downstream of a conserved Asp-His-His-Cys cysteine-rich domain. PMID: 19801377
