• It is the chemical modification of protein after
• Key role in functional Proteomics.
• They regulate activity, localization and
interaction with other cellular molecules such
as proteins, nucleic acids, lipids and cofactors.
Types of PTM’s
• Covalent Attachment
• Protein Folding
• Protein Degradation
• Insulin is synthesized in the cells and it is in
inactive form that it is can’t perform it’s
• For the proper functioning of the insulin, its post
translational modifications occurs that have
involve the removal of the part of protein to
convert it into three dimensional and fully active
• Addition of phosphate group to a protein.
• Principally on serine, threonine or tyrosine
• Also known as Phospho regulation.
• Critical role in cell cycle, growth, apoptosis
and signal transduction pathways.
ATP + protein ———————> phosphoprotein + ADP
• The covalent attachment of oligosaccharides
• Addition of glycosyl group or carbohydrate
group to a protein.
• Principally on Asparagine, hydroxylysine,
serine or threonine.
• Significant effect on protein folding,
conformation, distribution, stability and
• N-Linked glycans
– attached to nitrogen of Asparagine or arginine side
• O-Linked glycans
– attached to hydroxy oxygen of serine,threonine
• Phospho glycans
– linked through the phosphate of serine.
• C-Linked glycans
– Rare form, Sugar is added to a carbon on tryptophan
Classes of Glycans
• Ubiquitin is a small regulatory protein that can
be attached to the proteins and label them for
• Effects in cell cycle regulation, control of
proliferation and differentiation, programmed
cell death (apoptosis), DNA repair, immune
and inflammatory processes and organelle
• Nitrosyl (NO) group is added to the protein.
• NO a chemical messanger that reacts with free
cysteine residues to form S-nitrothiols.
• Used by cells to stabilize proteins, regulate
• Addition of methyl group to a protein.
• Usually at lysine or arginine residues.
• Binds on nitrogen and oxygen of proteins
• Methyl donor is S-adenosylmethionine (SAM)
• Enzyme for this is methyltransferase
• Methylation of lysine residues in histones in
DNA is important regulator of chromatin
• Addition of acetyl group to the nitrogen.
• Histones are acetylated on lysine residues in
the N-terminal tail as a part of gene
• Involved in regulation of transcription factors,
effector proteins, molecular chaperons and
• Methionine aminopeptidase (MAP) is an
enzyme responsible for N-terminal acetylation
• Lipidation attachment of a lipid group, such as
a fatty acid, covalently to a protein.
• In general, lipidation helps in cellular
localization and targeting signals, membrane
tethering and as mediator of protein-protein
phosphatidylinositol (GPI) anchor
• GPI anchors tether cell surface proteins to the
• GPI-anchored proteins are often localized to
cholesterol- and sphingolipid-rich lipids, which
act as signaling platforms on the plasma
• It is the attachment of myristoyl group a 14-
carbon saturated fatty acid (C14) to a protein.
• It is facilitated by N-myristoyltransferase (NMT)
and uses myristoyl-CoA as the substrate.
• It is addition of C16 palmitoyl group from
• Palmitoyl acyl transferases (PATs)enzyme
favors this step.
• Reversed by thioesterases
• Addition of a farnesyl (C15) or geranylgeranyl
(C20) group to proteins.
• Enzyme involved in this reaction is farnesyl
transferase (FT) or geranylgeranyl transferases
(GGT I and II).
• Disulfide bonds are covalent bonds formed
between two cysteine residues (R-S-S-R).
• These bonds contribute to the correct folding of
proteins as other elements of secondary
• Cleavage of peptide bonds by proteases.
• Examples of Proteases- Serine Proteases,
Cysteine Proteases, Aspartic acid Proteases.
• Involved in Antigen processing, Apoptosis, Cell
• Mass spectrometry
• HPLC analysis
• Incorporation of radioactive groups by addition to
– e.g., 75Se-labeling
isolation of proteins
• Antibody cross-reactivity
– e.g., antibody against phosphotyrosine
• Polyacrylamide gel electrophoresis (PAGE)
Identification of modifications