Last modified September 9, 2013
This subsection of the ‘Sequence annotation (Features)’ section specifies the position(s) and the type of covalently attached lipid group(s).
The covalent binding of a lipid group to a peptide chain, also known as lipidation, can affect the activity of the protein and/or alter its subcellular location. For instance, palmitoylation, myristoylation or prenylation of cytoplasmic proteins can promote their association with the inner face of the plasma membrane, while the addition of a GPI-anchor may serve to anchor extracellular proteins to the outer face of the plasma membrane.
Related keyword: Lipoprotein
Most frequent lipids have a specific keyword (see below)
The following types of lipidation are described in UniProtKB:
- GPI-anchor addition
- Lipidation of bacterial proteins (S-diacylglycerol)
- Other types of lipidation
N-myristoylation refers to the covalent attachment of myristate to an N-terminal glycine. This irreversible protein modification occurs co- translationally following the removal of the initiator methionine residue, which is also annotated. This modification promotes weak protein-membrane and protein-protein interactions.
We annotate experimentally determined N-myristoylation sites and sites predicted by NMT and NMT_NN predictors provided that the prediction is consistent with other known properties of the protein or that the protein belongs to a family in which this modification is known to occur.
Related keyword: Myristate
S-palmitoylation is the thioester linkage of long-chain fatty acids to cytoplasmic cysteine residues. S-palmitoylation can modulate interactions with other proteins and membranes and regulate protein trafficking and enzyme activity.
Related keyword: Palmitate
3. GPI-anchor addition
GPI-anchor addition refers to the linkage of glycosyl-phosphatidylinositol (GPI) to the C-terminus of extracellular proteins, which mediates their attachment to the plasma membrane. GPI-anchor addition takes place in the lumen of the endoplasmic reticulum.
We annotate experimentally determined sites of GPI-anchor addition, as well as sites predicted by the ‘big-Pi’ predictor, but only when the protein (or the family to which it belongs) is known to be modified in this way and the precise site of modification is unknown.
Related keyword: GPI-anchor
Prenylation is the thioether linkage of an isoprenoid lipid (farnesyl (C-15) or geranylgeranyl (C-20)) to a cytoplasmic cysteine at or near the C-terminus. These lipid groups mediate protein attachment to membranes and their addition is specified by the amino acid sequence motifs CAAX, CC or CAC at the C-terminus. Prenylated proteins are estimated to represent 0.5% of all intracellular proteins.
Prenylation of a cysteine in the CAAX context often leads to both proteolytic cleavage of the C-A bond and to the methylation of the new C-terminal cysteine residue. Both the cleaved propeptide and the accompanying methylation of the new C-terminal cysteine are annotated.
5. Lipidation of bacterial proteins (S-diacylglycerol)
Most bacterial lipoproteins are anchored to the outer plasma membrane by diacylglycerol linked to the side chain of an N-terminal cysteine via the sulfur atom. This modification is required for the cleavage of the signal peptide. The mature N-terminal chain is further palmitoylated.
6. Other examples of lipidation
O-octanoyl: attached to serine or threonine of secreted proteins.
S-archaeol: attached to cysteine of secreted proteins.
Cholesterol: attached to the C-terminus following cleavage of the
See also: Non-experimental qualifiers