Peptidein
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
- ↑ 1.0 1.1 Callaway, Ewen (2026-05-06). "Revealed: the mysterious 'dark' proteins that might play a big role in biology". Nature. doi:10.1038/d41586-026-01492-x. ISSN 1476-4687. PMID 42092205 Check
|pmid=value (help). - ↑ Ktori, Sophia (2026-05-06). "Microproteins and Peptideins Expand Boundaries of the Human Proteome". GEN - Genetic Engineering and Biotechnology News. Retrieved 2026-05-08.
- ↑ 3.0 3.1 3.2 Smith, Rhianna-lily (2026-05-07). "The Human Proteome Just Got 10% Bigger". Technology Networks. Retrieved 2026-05-08.
- ↑ 4.0 4.1 Callaway, Ewen (2025-01-29). "'Dark proteins' hiding in our cells could hold clues to cancer and other diseases". Nature. 637 (8048): 1038–1040. Bibcode:2025Natur.637.1038C. doi:10.1038/d41586-025-00217-w. ISSN 1476-4687. PMID 39880991 Check
|pmid=value (help). - ↑ Harley, Sadie (2026-05-06). "Dark proteome yields 1,785 new microproteins that could reshape disease research". Phys.org.
- ↑ Chothani, Sonia; Ruiz-Orera, Jorge; Tierney, Jack A S; Swirski, Michal I; Tjeldnes, Hakon; Kok, Leron W; Clauwaert, Jim; Deutsch, Eric W; Alba, M Mar; Aspden, Julie L; Baranov, Pavel V; Bazzini, Ariel Alejandro; Bruford, Elspeth A; Brunet, Marie A; Cardon, Tristan (2026-03-19). "An expanded reference catalog of translated open reading frames for biomedical research". Nucleic Acids Research. 54 (6). doi:10.1093/nar/gkag234. ISSN 0305-1048. PMC 13010147 Check
|pmc=value (help). PMID 41873765 Check|pmid=value (help). Unknown parameter|article-number=ignored (help) - ↑ Basrai, Munira A.; Hieter, Philip; Boeke, Jef D. (1997-08-01). "Small Open Reading Frames: Beautiful Needles in the Haystack". Genome Research. 7 (8): 768–771. doi:10.1101/gr.7.8.768. ISSN 1088-9051. PMID 9267801.
- ↑ 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. PMC 10073203 Check
|pmc=value (help). PMID 36543139 Check|pmid=value (help). Unknown parameter|s2cid=ignored (help); Unknown parameter|article-number=ignored (help) - ↑ 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. PMC 8831751 Check
|pmc=value (help). PMID 35154250 Check|pmid=value (help). Unknown parameter|article-number=ignored (help) - ↑ Zanet J, Benrabah E, Li T, Pélissier-Monier A, Chanut-Delalande H, Ronsin B, et al. (September 2015). "Pri sORF peptides induce selective proteasome-mediated protein processing" (PDF). Science. 349 (6254): 1356–1358. Bibcode:2015Sci...349.1356Z. doi:10.1126/science.aac5677. PMID 26383956. Unknown parameter
|s2cid=ignored (help) - ↑ 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. PMC 8928697 Check
|pmc=value (help). PMID 35300685 Check|pmid=value (help). - ↑ 12.0 12.1 Saghatelian, Alan; Couso, Juan Pablo (2015). "Discovery and characterization of smORF-encoded bioactive polypeptides". Nature Chemical Biology. 11 (12): 909–916. doi:10.1038/nchembio.1964. hdl:10261/191767. ISSN 1552-4450. PMC 4956473. PMID 26575237.
- ↑ 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". Nature. 571 (7763): 107–111. Bibcode:2019Natur.571..107O. doi:10.1038/s41586-019-1312-2. ISSN 0028-0836. PMC 7061489 Check
|pmc=value (help). PMID 31217582. - ↑ 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". Nature Chemical Biology. 16 (4): 458–468. doi:10.1038/s41589-019-0425-0. ISSN 1552-4450. PMC 7085969 Check
|pmc=value (help). PMID 31819274. - ↑ "Thousands of new proteins revealed in dark proteome". EurekAlert!. 2026-05-06. Retrieved 2026-05-08.
- ↑ 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". Nature: 1–13. doi:10.1038/s41586-026-10459-x. hdl:20.500.11850/800241. ISSN 1476-4687. PMID 42092140 Check
|pmid=value (help). - ↑ Oldach, Laurel (2026-05-06). "How many tiny proteins are in the human genome?". c&en. American Chemical Society.
This article "Peptidein" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:Peptidein. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.
