Evaluation of PE5 Entries on the Human Proteome Project Target List

Area of Science:

• Proteomics
• Genomics
• Bioinformatics

Background:

• The Human Proteome Organization (HUPO) Human Proteome Project (HPP) aims to identify protein-coding genes in the human genome.
• A subset of 76 human protein entries are currently annotated with PE5 in UniProtKB, indicating curator skepticism about their existence.
• The status of these PE5 entries is uncertain regarding their inclusion in the HPP target list.

Purpose of the Study:

• To evaluate the existence of 76 human protein entries with PE5 annotation.
• To determine if these entries warrant an upgrade to PE1-4 status in UniProtKB based on available evidence.
• To clarify the inclusion of these entries in the HUPO-HPP target list.

Main Methods:

• Systematic review of evidence from scientific literature.
• Analysis of data from reference proteomic and genomic databases.
• Comparative genome alignments across species to assess evolutionary conservation.

Main Results:

• Seventeen (17) entries demonstrated credible protein translation evidence and should be upgraded to PE1.
• Fifteen (15) entries lacked translation evidence but possessed transcription evidence, suggesting potential protein production.
• Forty-one (41) entries showed neither translation nor transcription evidence, with their protein-coding status remaining uncertain.
• Three (3) entries were confirmed as PE5 and should be excluded from the HPP target list.

Conclusions:

• A significant portion of PE5-annotated human protein entries possess evidence supporting their existence.
• The re-evaluation clarifies the status of these proteins, impacting the completeness of the human proteome dataset.
• Policy decisions are needed for entries lacking definitive translational or transcriptional evidence.