This document summarizes post-translational modifications (PTMs) of proteins. It discusses that there are over 400 types of PTMs that impact protein function. The three major PTMs discussed are phosphorylation, acetylation, and ubiquitination. Phosphorylation involves adding phosphate groups and is reversible, switching signaling proteins on and off. Acetylation involves adding acetyl groups via lysine acetyltransferase and occurs on thiol, hydroxyl, and amino groups. Ubiquitination involves adding ubiquitin and targets proteins for degradation by the proteasome. Disruptions to PTMs can lead to disease.

1. Post
translational
modification of
proteins

2. Introduction
 Posttranslational modifications (PTMs) refer to amino acid side chain
modification in some proteins after their biosynthesis
 These processes have a significant impact on the structure and function of
proteins
 Disruption in PTMs can lead to the dysfunction of vital biological processes and
hence to various diseases.
 PTM can be reversible or irreversible

3. Post translational protein modification

4.  There are more than 400 different types of PTMs affecting many aspects of
protein functions.
 Three main PTMs, based on the dbPTM database, are phosphorylation,
acetylation and ubiquitination
 PTMs are important components in cell signaling, as for example
when prohormones are converted to hormones.

5. Summarized information of major PTMs based on
the dbPTM database

6. PHOSPHORYLATION
 Reversible phosphorylation of proteins involves addition of a phosphate group on
serine, threonine, or tyrosine residues and is one of the important and extensively
studied PTM in both prokaryotes and eukaryotes.
 Several enzymes or signaling proteins are switched ‘on’ or ‘off’ by phosphorylation
or dephosphorylation
 phosphorylation is performed by enzymes called ‘kinases’, while
dephosphorylation is performed by ‘phosphatases’.
 Addition of a phosphate group can convert a previously uncharged pocket of
protein into a negatively charged and hydrophilic protein there by inducing
conformational changes in the protein.

7.  Addition of a phosphate group can convert a previously uncharged pocket of protein into a
negatively charged and hydrophilic protein thereby inducing conformational changes in the
protein.
 Phosphorylation has implications in several cellular processes, including cell cycle, growth,
apoptosis and signal transduction pathways
 One example is the activation of p53, a tumor suppressor protein. p53 is used in cancer
therapeutics and is activated by phosphorylation of its N-terminal by several kinases.

8. signaling proteins are switched ‘on’ or ‘off’ by
phosphorylation or dephosphorylation

9. ACETYLATION
 Acetylation is catalyzed via lysine acetyltransferase (KAT) and histone acetyltransferase (HAT)
enzymes.
 The atom to which the acetyl group is attached is usually denoted in the name of either the final
molecule or the enzyme that performs the acetylation.
 Acetylation can occur with thiol groups (sulfur), hydroxyl groups (oxygen), and often amino
groups (nitrogen).
 Acetyltransferases use acetyl CoA as a cofactor for adding an acetyl group (COCH3) to the ε-
amino group of lysine side chains, whereas deacetylases (HDACs) remove an acetyl group on
lysine side chains

11. UBIQUITINATION
 N-terminal ubiquitination involves the addition of a ubiquitin moiety to the free
α-amino group of the first residue of a protein.
 The N-terminal ubiquitin may serve as a target for polyubiquitination, which is a
well-known degradation signal recognized by the 26S proteasome complex.
 The addition of ubiquitin to the N-terminus of a target protein requires the
same enzymatic machinery as ubiquitination of internal residues in the protein
sequence, including ubiquitin activating, conjugating, and ligating enzymes.

12.  There are two enzymes in the ubiquitin pathway, Ube2w and Huwe1, are reported to have the
ability for N-terminal ubiquitination
 Ube2w is an E2 ligase that conjugates ubiquitin to the N-terminal residue of Ataxin-3 and tau
protein
 Huwe1 is the ubiquitin E3 ligase responsible for MyoD N-terminal ubiquitination.
 It was reported to play an important role in the nervous system, including neural progenitor
proliferation, differentiation, cell migration, axon development, and inhibitory neurotransmission

14. THE END