Biology:PNMA2
Paraneoplastic antigen Ma2 (PNMA2), also known as Ma2 or MM2, is a protein that in humans is encoded by the PNMA2 gene on chromosome 8 (8p21.2).[1][2] The gene encodes an approximately 40 kDa onconeuronal protein predominantly expressed in neurons of the central nervous system[3] and belongs to the paraneoplastic Ma antigen (PNMA) protein family.[4]
PNMA2 can self-assemble into virus-like particles which closely resemble the capsids of HIV-1.[5] These capsids can act as an extracellular antigen and have been found to be capable of generating an autoimmune response.[3] The conserved virus-like aspects of PNMA2 is shared with other retrotransposons-dertived mammalian proteins such as Arc and PEG10.
Evolution
The PNMA2 gene is located on the short arm of human chromosome 8 in a cytogenetic band.[2][6] It comprises three exons, the third of which encodes the entire open reading frame.[3] Phylogenomic analysis suggests PNMA2 was co-opted from an LTR retrotransposon of the Ty3/mdg4 family in the common ancestor of placental mammals approximately 100 mya. It appears across all major placental mammal lineages except marsupials.[3] The promoter region lies 150 base pairs from the neighboring DPYSL2 gene, with which it likely shares a bidirectional promoter, this may have facilitated the gene's co-option.[3]
Clinical significance
Normally sequestered within the immune-privileged CNS, PNMA2 can be ectopically expressed by certain peripheral tumors, leading to release of virus-like capsids into systemic circulation, and this can trigger an autoimmune response. The resulting autoantibodies preferentially target the epitopes of the capsid and cross-react with normal PNMA2 in the brain, causing what is known as "anti-Ma2 paraneoplastic neurological syndrome" (Ma2-PNS).[1][7]
See also
References
- ↑ 1.0 1.1 "A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer". N Engl J Med 340 (23): 1788–95. Jun 1999. doi:10.1056/NEJM199906103402303. PMID 10362822.
- ↑ 2.0 2.1 "Entrez Gene: PNMA2 paraneoplastic antigen MA2". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=10687.
- ↑ 3.0 3.1 3.2 3.3 3.4 "PNMA2 forms immunogenic non-enveloped virus-like capsids associated with paraneoplastic neurological syndrome". Cell 187 (4): 831–845.e19. Feb 2024. doi:10.1016/j.cell.2024.01.009. PMID 38301645.
- ↑ "Molecular and clinical diversity in paraneoplastic immunity to Ma proteins". Ann Neurol 50 (3): 339–48. Sep 2001. doi:10.1002/ana.1288. PMID 11558790.
- ↑ "Human paraneoplastic antigen Ma2 (PNMA2) forms icosahedral capsids that can be engineered for mRNA delivery". Proc Natl Acad Sci U S A 121 (11). Mar 2024. doi:10.1073/pnas.2307812120. PMID 38437549.
- ↑ "OMIM Entry 603970 — Paraneoplastic Ma Antigen 2; PNMA2". https://www.omim.org/entry/603970.
- ↑ "Clinical analysis of anti-Ma2-associated encephalitis". Brain 127 (Pt 8): 1831–44. Aug 2004. doi:10.1093/brain/awh203. PMID 15215214. https://academic.oup.com/brain/article/127/8/1831/297516.
Further reading
- "Generation and analysis of 280,000 human expressed sequence tags". Genome Res. 6 (9): 807–28. 1997. doi:10.1101/gr.6.9.807. PMID 8889549.
- "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 5 (6): 355–64. 1999. doi:10.1093/dnares/5.6.355. PMID 10048485.
- "Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders". Brain 122 (1): 27–39. 1999. doi:10.1093/brain/122.1.27. PMID 10050892.
- "Molecular and clinical diversity in paraneoplastic immunity to Ma proteins". Ann. Neurol. 50 (3): 339–48. 2001. doi:10.1002/ana.1288. PMID 11558790.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. 2004. doi:10.1038/ng1285. PMID 14702039.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. 2006. doi:10.1101/gr.4039406. PMID 16344560.
- "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. 2007. doi:10.1038/msb4100134. PMID 17353931.
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