Biology:Peptidein

From HandWiki

A peptidein is a small molecule made up of amino acids similar in appearance and biomechanical role to proteins.[1] More than 1,700 types of peptideins have been identified, most of which are of unknown functions, but some are implicated with genetic diseases and cancer.[2] Popularly called the "dark proteome"[3] or "dark proteins"[4] due to their elusive identity, they are a type of microproteins, and were identified by an international team of scientists led by Sebastiaan van Heesch of the Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands, in 2026.[5]

Discovery

In 2022, Sonia Chothani at the Duke-NUS Medical School and Genome Institute of Singapore and Jorge Ruiz-Orera at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany, initiated an international project called TransCODE Consortium. The project aimed at identifying all the proteins produced (encoded) from a small open reading frame (sORF or smORF) in the human genome.[6] Hundreds to thousands of sORFs were estimated to exist in different organisms, and were named as such by Munira A. Basrai, Philip Hieter and Jef D. Boeke of the Johns Hopkins University School of Medicine, in 1997.[7] Some sORF are so small,[8] usually shorter than 100 codons,[9] that they were believed to have no protein-coding genes to make functional peptides.[10][11] However, were different some genetic diseases and cancers in humans were found to be associated with these short DNA sequences.[12][13] Association with diseases indicated that they must produce some kind of proteins, hundreds of them, but impossible to detect them directly.[14] For their elusive nature, they were known as the "dark proteome"[3] or "dark proteins".[4]

In 2026, the TransCODE Consortium announced the first complete identification of microproteins and published it in the journal Nature, from a research led by Sebastiaan van Heesch of the Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands, and co-led by John Prensner (University of Michigan Medical School) and Robert Moritz (Institute for Systems Biology).[15] The scientists gave the name "peptidein" for the protein-like molecules.[1] By definition, they are too small to be named proteins,[12] as they explained:

We develop an annotation framework for ncORF-encoded microproteins as human proteins and codify the new conceptual model of 'peptideins' as microproteins that have indeterminate potential as functional proteins... To bring formal reference gene annotation status to less-well-characterized microproteins, we introduce 'peptidein' as a classification scheme, recognized by our consortia, to exist alongside conventional proteins. To illustrate that further characterization of a peptidein may elevate its classification, we use functional genomics and evolutionary constraint to pinpoint examples that exhibit a signature consistent with a protein-coding gene.[16]

The TransCODE Consortium identified 1,785 peptideins. The human genome contain about 19,500 functional proteins, thus peptideins adds 10% more of functional genes.[3] The number is still preliminary, as Moritz explained that there may be thousand more peptideins to be identified and could double the human proteome.[17]

References

  1. ↑ 1.0 1.1 Callaway, Ewen (2026-05-06). "Revealed: the mysterious 'dark' proteins that might play a big role in biology" (in en). Nature. doi:10.1038/d41586-026-01492-x. ISSN 1476-4687. PMID 42092205. https://www.nature.com/articles/d41586-026-01492-x. 
  2. ↑ Ktori, Sophia (2026-05-06). "Microproteins and Peptideins Expand Boundaries of the Human Proteome" (in en-US). https://www.genengnews.com/topics/omics/microproteins-and-peptideins-expand-boundaries-of-the-human-proteome/. 
  3. ↑ 3.0 3.1 3.2 Smith, Rhianna-lily (2026-05-07). "The Human Proteome Just Got 10% Bigger" (in en). http://www.technologynetworks.com/tn/news/the-human-proteome-just-got-10-bigger-412414. 
  4. ↑ 4.0 4.1 Callaway, Ewen (2025-01-29). "'Dark proteins' hiding in our cells could hold clues to cancer and other diseases" (in en). Nature 637 (8048): 1038–1040. doi:10.1038/d41586-025-00217-w. ISSN 1476-4687. PMID 39880991. Bibcode: 2025Natur.637.1038C. https://www.nature.com/articles/d41586-025-00217-w. 
  5. ↑ Harley, Sadie (2026-05-06). "Dark proteome yields 1,785 new microproteins that could reshape disease research". https://phys.org/news/2026-05-dark-proteome-yields-microproteins-reshape.html. 
  6. ↑ Chothani, Sonia; Ruiz-Orera, Jorge; Tierney, Jack A S; Swirski, Michal I; Tjeldnes, Hakon; Kok, Leron W; Clauwaert, Jim; Deutsch, Eric W et al. (2026-03-19). "An expanded reference catalog of translated open reading frames for biomedical research" (in en). Nucleic Acids Research 54 (6). doi:10.1093/nar/gkag234. ISSN 0305-1048. PMID 41873765. 
  7. ↑ Basrai, Munira A.; Hieter, Philip; Boeke, Jef D. (1997-08-01). "Small Open Reading Frames: Beautiful Needles in the Haystack" (in en). Genome Research 7 (8): 768–771. doi:10.1101/gr.7.8.768. ISSN 1088-9051. PMID 9267801. 
  8. ↑ Vakirlis, Nikolaos; Vance, Zoe; Duggan, Kate M.; McLysaght, Aoife (2022). "De novo birth of functional microproteins in the human lineage". Cell Reports 41 (12). doi:10.1016/j.celrep.2022.111808. PMID 36543139. 
  9. ↑ Kute, Preeti Madhav; Soukarieh, Omar; Tjeldnes, Håkon; Trégouët, David-Alexandre; Valen, Eivind (2022). "Small Open Reading Frames, How to Find Them and Determine Their Function". Frontiers in Genetics 12. doi:10.3389/fgene.2021.796060. PMID 35154250. 
  10. ↑ "Pri sORF peptides induce selective proteasome-mediated protein processing". Science 349 (6254): 1356–1358. September 2015. doi:10.1126/science.aac5677. PMID 26383956. Bibcode: 2015Sci...349.1356Z. https://hal.inrae.fr/hal-04767052v1/file/zanet%202015.pdf. 
  11. ↑ Leong, Alyssa Zi-Xin; Lee, Pey Yee; Mohtar, M. Aiman; Syafruddin, Saiful Effendi; Pung, Yuh-Fen; Low, Teck Yew (2022). "Short open reading frames (sORFs) and microproteins: an update on their identification and validation measures". Journal of Biomedical Science 29 (1): 19. doi:10.1186/s12929-022-00802-5. PMID 35300685. 
  12. ↑ 12.0 12.1 Saghatelian, Alan; Couso, Juan Pablo (2015). "Discovery and characterization of smORF-encoded bioactive polypeptides" (in en). Nature Chemical Biology 11 (12): 909–916. doi:10.1038/nchembio.1964. ISSN 1552-4450. PMID 26575237. 
  13. ↑ Oz-Levi, Danit; Olender, Tsviya; Bar-Joseph, Ifat; Zhu, Yiwen; Marek-Yagel, Dina; Barozzi, Iros; Osterwalder, Marco; Alkelai, Anna et al. (2019). "Noncoding deletions reveal a gene that is critical for intestinal function" (in en). Nature 571 (7763): 107–111. doi:10.1038/s41586-019-1312-2. ISSN 0028-0836. PMID 31217582. Bibcode: 2019Natur.571..107O. 
  14. ↑ Martinez, Thomas F.; Chu, Qian; Donaldson, Cynthia; Tan, Dan; Shokhirev, Maxim N.; Saghatelian, Alan (2020). "Accurate annotation of human protein-coding small open reading frames" (in en). Nature Chemical Biology 16 (4): 458–468. doi:10.1038/s41589-019-0425-0. ISSN 1552-4450. PMID 31819274. 
  15. ↑ "Thousands of new proteins revealed in dark proteome" (in en). 2026-05-06. https://www.eurekalert.org/news-releases/1126540. 
  16. ↑ Deutsch, Eric W.; Kok, Leron W.; Mudge, Jonathan M.; Valls, Cristian F.; Jungreis, Irwin; Ruiz-Orera, Jorge; Sun, Zhi; Kusebauch, Ulrike et al. (2026-05-06). "Expanding the human proteome with microproteins and peptideins" (in en). Nature: 1–13. doi:10.1038/s41586-026-10459-x. ISSN 1476-4687. PMID 42092140. https://www.nature.com/articles/s41586-026-10459-x. 
  17. ↑ Oldach, Laurel (2026-05-06). "How many tiny proteins are in the human genome?". American Chemical Society. https://cen.acs.org/articles/104/web/2026/05/tiny-proteins-human-genome.html. 



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