Q.5 Which one of the following aminoacids in proteins does NOT undergo phosphorylation?
(A) Ser (B) Thr (C) Pro (D) Tyr
Standard protein phosphorylation targets three key amino acids with hydroxyl groups, while proline’s unique structure prevents modification. This MCQ tests fundamental knowledge of post-translational modifications critical for biochemistry and biotech signaling pathways.
Correct Answer
(C) Pro does NOT undergo phosphorylation. Proline’s cyclic pyrrolidine ring locks the -OH group in its side chain, sterically hindering kinase access to the alpha nitrogen and carboxyl for phosphate attachment. Unlike Ser, Thr, and Tyr, Pro lacks a free hydroxyl amenable to standard O-phosphorylation.
Option Analysis
(A) Ser
Serine, the most common target (~76% of sites), features a primary alcohol (-CH2OH) easily phosphorylated by Ser/Thr kinases like PKA and MAPK in signaling cascades.
(B) Thr
Threonine (~20% sites) has a secondary alcohol (-CH(OH)CH3), targeted by kinases like CDK and AKT for cell cycle and survival regulation.
(D) Tyr
Tyrosine (~4% sites) possesses a phenolic -OH, phosphorylated by RTKs like EGFR in growth factor pathways, often harder to detect due to lower abundance.
Phosphorylation Mechanism
Kinases transfer ATP’s γ-phosphate to the hydroxyl oxygen, creating a phosphoester bond that introduces negative charge, altering protein conformation and interactions. Proline’s imino acid nature disrupts secondary structure, evading this regulation.


