Ser5

Ser5 refers to the serine residue at position 5 in a protein sequence, a notation commonly used in protein annotation. In many biological contexts, Ser5 specifically denotes the serine located in the fifth position of a peptide or in the repeats of a larger domain, and it is often highlighted because its phosphorylation state can regulate function.

The most widely studied use of the term concerns the serine-5 residue within the C-terminal domain (CTD) of RNA polymerase II. The CTD comprises repeats of the heptad motif YSPTSPS, and Ser5 is the fifth residue in each repeat. Phosphorylation at Ser5 (Ser5P) is a key regulatory mark during transcription initiation and promoter clearance. This modification is primarily carried out by the kinase CDK7, a component of TFIIH, and it facilitates recruitment of 5' capping enzymes and other initiation factors. As transcription progresses into elongation, Ser2 becomes the predominant phosphorylation site, while Ser5 phosphorylation often declines along the gene body.

Enzymatic removal of the Ser5 phosphate is achieved by phosphatases such as Fcp1 and Ssu72, enabling the transition from initiation to elongation and subsequent processing steps. The number of CTD repeats varies by organism (for example, about 52 in humans and fewer in yeast), but the pattern of Ser5 phosphorylation remains a central feature of transcriptional regulation and a common genomic marker in studies of transcription initiation.

Beyond the Pol II CTD, Ser5 can denote a serine at position 5 in other proteins, where the residue’s identity and modification state may influence structure, activity, or interactions.