Annotating proteins from endoplasmic reticulum and Golgi apparatus in eukaryotic proteomes

Area of Science:

• Cell Biology
• Bioinformatics
• Proteomics

Background:

• Protein sub-cellular localization is crucial for function and often regulated by sequence motifs.
• Endoplasmic reticulum (ER) and Golgi apparatus are key organelles involved in protein processing and transport.
• Homology transfer is a method used to infer protein function or localization based on sequence similarity.

Purpose of the Study:

• To analyze the accuracy of experimentally characterized ER/Golgi retrieval motifs.
• To investigate the reliability of homology transfer for inferring protein localization.
• To estimate the probability of protein localization given specific retrieval motifs.

Main Methods:

• Analysis of experimentally validated ER/Golgi retrieval motifs.
• Estimation of motif specificity and localization probability.
• Rigorous assessment of homology transfer accuracy and coverage using sequence similarity.
• Proteome-wide annotation of ER and Golgi proteins.

Main Results:

• C-terminal ER retrieval motifs KDEL, HDEL, and AIAKE showed high specificity.
• Provided probability estimates for localization based on motif presence.
• Annotated 3304 ER (3182 membrane) and 1853 Golgi (759 membrane) proteins across proteomes.
• Identified additional putative 5157 globular and 3941 membrane ER or Golgi proteins.
• Each experimental annotation yielded 1-3 high-accuracy and 5-6 low-accuracy homology transfers.

Conclusions:

• Specific C-terminal motifs enhance the accuracy of predicting ER localization.
• Homology transfer, combined with motif analysis, is a powerful tool for large-scale protein localization prediction.
• The number of annotated proteins is expected to grow with new experimental data.