ProteinIsoformen

Protein isoformen are distinct protein products produced from a single gene. They arise when a gene gives rise to multiple related proteins, expanding functional diversity without increasing genomic content. The most common source is alternative splicing of the primary transcript, but isoforms can also result from alternative promoter usage, alternative transcription termination, or proteolytic processing and post-translational modifications that yield different mature proteins.

Mechanisms generating isoforms include different exon inclusion or skipping, use of alternative start or stop codons, and domain shuffling. Resulting isoforms may differ in length, domain composition, subcellular localization signals, interaction motifs, or enzymatic activity. Such variations can alter stability, regulation, and partner interactions, leading to distinct cellular roles. Isoforms often exhibit tissue- or development-specific expression patterns, enabling precise control of biological processes.

Biological significance of protein isoforms is wide-ranging. They can fine-tune signaling pathways, enable functional diversification within a gene family, and provide mechanisms for rapid adaptation to physiological needs. Misregulated isoform expression has been linked to diseases, including cancer, neurodegenerative disorders, and metabolic conditions. In some cases, isoform-specific functions are exploited therapeutically, or isoform dynamics are targeted to modulate disease progression.

Discovery and annotation rely on transcriptomic and proteomic evidence. RNA sequencing identifies alternative transcripts, while proteomics and mass spectrometry confirm corresponding protein products. Public databases such as Ensembl, RefSeq, and UniProt curate isoforms with evidence codes, though annotation quality varies. Challenges include accurately quantifying isoforms, distinguishing highly similar sequences, and obtaining isoform-specific reagents.