Palmitoylation is the covalent attachment of fatty acids, such as
palmitic acid, to cysteine and less frequently to serine and threonine
residues of proteins, which are typically membrane proteins. The
precise function of palmitoylation depends on the particular protein
Palmitoylation enhances the hydrophobicity of
proteins and contributes to their membrane association. Palmitoylation
also appears to play a significant role in subcellular trafficking of
proteins between membrane compartments, as well as in modulating
protein–protein interactions. In contrast to prenylation and
myristoylation, palmitoylation is usually reversible (because the bond
between palmitic acid and protein is often a thioester bond). The
reverse reaction is catalysed by palmitoyl protein thioesterases.
Because palmitoylation is a dynamic, post-translational process, it is
believed to be employed by the cell to alter the subcellular
localization, protein–protein interactions, or binding capacities of
An example of a protein that undergoes palmitoylation is
hemagglutinin, a membrane glycoprotein used by influenza to attach to
host cell receptors. The palmitoylation cycles of a wide array of
enzymes have been characterized in the past few years, including
H-Ras, Gsα, the β2-adrenergic receptor, and endothelial nitric oxide
synthase (eNOS). Another example is the major signaling protein Wnt,
which is modified by a palmitoleoyl group at a serine. This is a type
of O-acylation and is mediated by a membrane-bound
O-acyltransferase. In signal transduction via G protein,
palmitoylation of the α subunit, prenylation of the γ subunit, and
myristoylation is involved in tethering the G protein to the inner
surface of the plasma membrane so that the G protein can interact with
1 The palmitoylome
2 In synaptic plasticity
3 See also
5 Further reading
6 External links
A meta-analysis of 15 studies produced a compendium of approximately
2,000 mammalian proteins that are palmitoylated. The highest
associations of the palmitoylome are with cancers and disorders of the
nervous system. Approximately 40% of synaptic proteins were found in
In synaptic plasticity
Scientists have appreciated the significance of attaching long
hydrophobic chains to specific proteins in cell signaling pathways. A
good example of its significance is in the clustering of proteins in
the synapse. A major mediator of protein clustering in the synapse is
the postsynaptic density (95kD) protein PSD-95. When this protein is
palmitoylated it is restricted to the membrane. This restriction to
the membrane allows it to bind to and cluster ion channels in the
postsynaptic membrane. Also, in the presynaptic neuron, palmitoylation
SNAP-25 directs it to partition in the cell membrane  and allows
SNARE complex to dissociate during vesicle fusion. This provides a
role for palmitoylation in regulating neurotransmitter release.
Palmitoylation of delta catenin seems to coordinate activity-dependent
changes in synaptic adhesion molecules, synapse structure, and
receptor localizations that are involved in memory formation.
Palmitoylation of gephyrin has been reported to influence GABAergic
^ a b Dejanovic B, Semtner M, Ebert S, Lamkemeyer T, Neuser F,
Lüscher B, Meier JC, Schwarz G (July 2014). "
gephyrin controls receptor clustering and plasticity of GABAergic
synapses". PLOS Biology. 12 (7): e1001908.
doi:10.1371/journal.pbio.1001908. PMC 4099074 .
^ Linder, M.E., "Reversible modification of proteins with
thioester-linked fatty acids," Protein Lipidation, F. Tamanoi and D.S.
Sigman, eds., pp. 215-40 (San Diego, CA: Academic Press, 2000).
^ Rocks O, Peyker A, Kahms M, Verveer PJ, Koerner C, Lumbierres M,
Kuhlmann J, Waldmann H, Wittinghofer A, Bastiaens PI (2005). "An
acylation cycle regulates localization and activity of palmitoylated
Ras isoforms". Science. 307 (5716): 1746–1752.
doi:10.1126/science.1105654. PMID 15705808.
^ Basu, J., "Protein palmitoylation and dynamic modulation of protein
function," Current Science, Vol. 87, No. 2, pp. 212-17 (25 July 2004),
^ "INFLUENZA VIRUSES (ORTHOMYXOVIRIDAE)". Encyclopedia of Virology:
^ Takada R, Satomi Y, Kurata T, Ueno N, Norioka S, Kondoh H, Takao T,
Takada S (2006). "Monounsaturated fatty acid modification of Wnt
protein: its role in Wnt secretion". Dev Cell. 11 (6): 791–801.
doi:10.1016/j.devcel.2006.10.003. PMID 17141155.
^ Wall, MA; Coleman, DE; Lee, E; Iñiguez-Lluhi, JA; Posner, BA;
Gilman, AG; Sprang, SR (Dec 15, 1995). "The structure of the G protein
heterotrimer Gi alpha 1 beta 1 gamma 2". Cell. 83 (6): 1047–58.
doi:10.1016/0092-8674(95)90220-1. PMID 8521505.
^ Sanders SS, Martin DD, Butland SL, Lavallée-Adam M, Calzolari D,
Kay C, Yates JR, Hayden MR (August 2015). "Curation of the Mammalian
Palmitoylome Indicates a Pivotal Role for
Palmitoylation in Diseases
and Disorders of the Nervous System and Cancers". PLoS Computational
Biology. 11 (8): e1004405. doi:10.1371/journal.pcbi.1004405.
PMC 4537140 . PMID 26275289.
^ Greaves, Jennifer (March 2011). "Differential palmitoylation
regulates intracellular patterning of SNAP25". Journal of Cell
Science. 124 (8): 1351–1360. doi:10.1242/jcs.079095.
PMC 3065388 . PMID 21429935.
^ "Molecular Mechanisms of Synaptogenesis." Edited by Alexander
Dityatev and Alaa El-Husseini. Springer: New York, NY. 2006. pg. 72-75
^ Brigidi GS, Sun Y, Beccano-Kelly D, Pitman K, Jobasser M, Borgland
SL, Milnerwood AJ, Bamji SX (January 23, 2014). "
[delta]-catenin by DHHC5 mediates activity-induced synapse
plasticity". Nature Neuroscience. 17: 522–532.
Smotrys J, Linder A (2004). "
Palmitoylation of Intracellular Signaling
Proteins: Regulation and Function". Annu Rev Biochem. 73: 559–87.
Resh, M. (2006) "
Palmitoylation of Ligands, Receptors, and
Intracellular Signaling Molecules". Sci STK. 359 October 31.
Linder M, Deschenes R (2007). "Palmitoylation: policing protein
stability and traffic". Nature Reviews Molecular Cell Biology. 8:
74–84. doi:10.1038/nrm2084. PMID 17183362.
Palmitoylation Site Prediction with a Clustering and
Swisspalm - S-Palmi