PNMA2

PNMA2
Identifiers
Aliases	PNMA2, MA2, MM2, RGAG2, paraneoplastic Ma antigen 2, PNMA family member 2
External IDs	OMIM: 603970; MGI: 2444129; GeneCards: PNMA2
Gene location (Human) Chr. Chromosome 8 (human) Band 8p21.2 Start 26,504,701 bp End 26,514,092 bp
Gene location (Mouse) Chr. Chromosome 14 (mouse) Band 14|14 D1 Start 67,148,619 bp End 67,158,472 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in orbitofrontal cortex middle temporal gyrus postcentral gyrus superior frontal gyrus Brodmann area 46 Brodmann area 23 superior vestibular nucleus lateral nuclear group of thalamus pons endothelial cell Top expressed in ventromedial nucleus lumbar spinal ganglion temporal lobe amygdala lateral septal nucleus anterior amygdaloid area lateral hypothalamus facial motor nucleus hippocampus proper substantia nigra More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component nucleus nucleolus Biological process positive regulation of apoptotic process Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 10687 239157 Ensembl ENSG00000240694 ENSMUSG00000046204 UniProt Q9UL42 Q8BHK0 RefSeq (mRNA) NM_007257 NM_175498 RefSeq (protein) NP_009188 NP_780707 Location (UCSC) Chr 8: 26.5 – 26.51 Mb Chr 14: 67.15 – 67.16 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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). The gene encodes an approximately 40 kDa onconeuronal protein predominantly expressed in neurons of the central nervous system and belongs to the paraneoplastic Ma antigen (PNMA) protein family.

PNMA2 can self-assemble into virus-like particles which closely resemble the capsids of HIV-1. These capsids can act as an extracellular antigen and have been found to be capable of generating an autoimmune response. 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. It comprises three exons, the third of which encodes the entire open reading frame. 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. 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.

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).

See also

• MER41
• HEMO protein

Further reading

• Hillier LD, Lennon G, Becker M, et al. (1997). "Generation and analysis of 280,000 human expressed sequence tags". Genome Res. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549.
• Nagase T, Ishikawa K, Suyama M, et al. (1999). "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. doi:10.1093/dnares/5.6.355. PMID 10048485.
• Dalmau J, Gultekin SH, Voltz R, et al. (1999). "Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders". Brain. 122 (1): 27–39. doi:10.1093/brain/122.1.27. PMID 10050892.
• Rosenfeld MR, Eichen JG, Wade DF, et al. (2001). "Molecular and clinical diversity in paraneoplastic immunity to Ma proteins". Ann. Neurol. 50 (3): 339–48. doi:10.1002/ana.1288. PMID 11558790. S2CID 24518861.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.