Page last updated: 2024-10-24

serine C-palmitoyltransferase complex

Definition

Target type: cellularcomponent

An enzyme complex that catalyzes the transfer of a palmitoyl on to serine, forming 3-dehydro-D-sphinganine. [PMID:19416851]

The serine C-palmitoyltransferase complex is a multi-protein assembly responsible for attaching palmitate, a 16-carbon fatty acid, to serine residues on target proteins. This process, known as S-palmitoylation, is crucial for regulating protein localization, membrane association, and signaling pathways. The exact composition of the complex can vary depending on the cell type and specific target protein. However, key components often include:

**1. DHHC-containing proteins:** These are the catalytic subunits of the complex, responsible for transferring palmitate from palmitoyl-CoA to the target protein. DHHC proteins have a conserved Asp-His-His-Cys (DHHC) motif within their active site, which is essential for enzymatic activity. Multiple DHHC isoforms exist, each with unique substrate specificity and cellular localization.

**2. Scaffolding proteins:** These proteins provide structural support and facilitate the assembly of the complex. They can interact with both DHHC proteins and target proteins, bringing them into proximity for efficient palmitoylation. Examples include:

* **G protein-coupled receptor kinases (GRKs):** These kinases are known to interact with certain DHHC proteins and regulate their activity.
* **Palmitoyl-protein thioesterases (PPTs):** These enzymes remove palmitate from target proteins, counteracting the action of the palmitoyltransferase complex.

**3. Target proteins:** The specific proteins that are palmitoylated by the complex. These proteins can be diverse and include:

* **Membrane receptors:** Palmitoylation can regulate their localization and signaling activity.
* **Signaling proteins:** Palmitoylation can modulate their interactions with other proteins and their activity.
* **Cytoskeletal proteins:** Palmitoylation can influence their assembly and dynamics.

**4. Additional factors:** The complex can also be regulated by other factors, such as:

* **Lipid rafts:** These specialized membrane domains are enriched in cholesterol and sphingolipids, and they can influence the assembly and activity of the palmitoyltransferase complex.
* **Post-translational modifications:** Phosphorylation and ubiquitination of the complex components can also regulate their activity.

The precise mechanism of palmitoylation by the serine C-palmitoyltransferase complex is still under investigation. However, it is believed that the process involves a series of steps, including:

1. **Substrate recognition:** The DHHC protein recognizes and binds to the target protein.
2. **Palmitoyl-CoA binding:** The DHHC protein binds to palmitoyl-CoA, the donor of the palmitate moiety.
3. **Palmitate transfer:** The DHHC protein catalyzes the transfer of palmitate from palmitoyl-CoA to the serine residue on the target protein.
4. **Complex disassembly:** After palmitoylation, the complex may disassemble, allowing the DHHC protein to palmitoylate other targets.

The serine C-palmitoyltransferase complex plays a crucial role in cellular function by regulating protein localization, activity, and signaling pathways. Its dynamic composition and regulation make it a complex and fascinating target for further research.'
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Proteins (2)

ProteinDefinitionTaxonomy
Serine palmitoyltransferase 2A serine palmitoyltransferase 2 that is encoded in the genome of human. [PRO:CNA]Homo sapiens (human)
Serine palmitoyltransferase 1A serine palmitoyltransferase 1 that is encoded in the genome of human. [PRO:CNA]Homo sapiens (human)

Compounds (1)

CompoundDefinitionClassesRoles
thermozymocidinthermozymocidin: a serine palmitoyltransferase inhibitor; FTY720 is an analogalpha-amino fatty acid;
hydroxy monocarboxylic acid;
non-proteinogenic alpha-amino acid;
sphingoid
antifungal agent;
antimicrobial agent;
antineoplastic agent;
apoptosis inducer;
EC 2.3.1.50 (serine C-palmitoyltransferase) inhibitor;
fungal metabolite;
immunosuppressive agent