PiggyBac Transposable Element Derived 5

PGBD5
Identifiers
Aliases	PGBD5 , piggyBac transposable element derived 5, PiggyBac Transposable Element Derived 5
External IDs	OMIM: 616791; MGI: 2429955; HomoloGene: 11583; GeneCards: PGBD5; OMA:PGBD5 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1q42.13 Start 230,314,490 bp [1] End 230,426,332 bp [1]
Gene location (Mouse) Chr. Chromosome 8 (mouse) [2] Band 8|8 E2 Start 125,095,788 bp [2] End 125,166,397 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in frontal pole entorhinal cortex middle temporal gyrus postcentral gyrus superior frontal gyrus Brodmann area 46 Brodmann area 10 orbitofrontal cortex cerebellar vermis Brodmann area 23 Top expressed in dentate gyrus dentate gyrus of hippocampal formation granule cell piriform cortex olfactory tubercle hippocampus proper dorsal striatum cingulate gyrus primary visual cortex medial dorsal nucleus prefrontal cortex More reference expression data BioGPS n/a
Gene ontology Molecular function nuclease activity endonuclease activity hydrolase activity transposase activity Cellular component nucleus Biological process transposition nucleic acid phosphodiester bond hydrolysis non-replicative transposition, DNA-mediated Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 79605 209966 Ensembl ENSG00000177614 ENSMUSG00000050751 UniProt Q8N414 D3YZI9 RefSeq (mRNA) NM_024554 NM_001258311 NM_171824 RefSeq (protein) NP_001245240 NP_741958 Location (UCSC) Chr 1: 230.31 – 230.43 Mb Chr 8: 125.1 – 125.17 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

PiggyBac Transposable Element Derived 5 is an enzyme that in humans is encoded by the PGBD5 gene. ^[5] PGBD5 is a DNA transposase related to the ancient PiggyBac transposase first identified in the cabbage looper moth, Trichoplusia ni. ^[6] The gene is believed to have been domesticated over 500 million years ago in the common ancestor of cephalochordates and vertebrates. ^[7] The putative catalytic triad of the protein composed of three aspartic acid residues is conserved among PGBD5-like genes through evolution, ^[8] and is distinct from other PiggyBac-like genes. ^[7] PGBD5 has been shown to be able to transpose DNA in a sequence-specific, cut-and-paste fashion. ^[8] PGBD5 has also been proposed to mediate site-specific DNA rearrangements in human tumors. ^[9]

Human PGBD5 can mobilize the insect PiggyBac transposons in human cell culture. ^[10]

Expression in the brain

In mature mice brain tissue PGBD5 is found primarily in regions of the olfactory bulb, hippocampus, and cerebellum. In embryonic mice brain tissue PGBD5 is found not only in the medial pallium and prepontine isthmus, which are embryonic brain areas that give rise to the development of the hippocampus and cerebellum but also in areas in the embryonic brain that give rise to the hypothalamus and medulla. ^{[11] [ better source needed ]}

Disease Associations

PGBD5 is expressed in the majority of human pediatric solid tumors. ^[12] It's upregulated in sporadic Creutzfeldt-Jakob disease. ^[13] PGBD5 is associated with frontotemporal dementia, where it gets most expressed in neurons, followed by ogliodendrocytes, mature astrocytes, fetal astrocytes, endothelial cells and then microglia/macrophages. ^[14]

References

1. GRCh38: Ensembl release 89: ENSG00000177614 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000050751 – Ensembl, May 2017
3. '"`UNIQ--templatestyles-00000006-QINU`"' "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. '"`UNIQ--templatestyles-00000008-QINU`"' "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "PGBD5 piggyBac transposable element derived 5 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 8 April 2017.
6. Toman J (1979). "A course to pursue". Nursing Times. 75 (17): 694–695. PMID   255260.
7. Pavelitz T, Gray LT, Padilla SL, Bailey AD, Weiner AM (November 2013). "PGBD5: a neural-specific intron-containing piggyBac transposase domesticated over 500 million years ago and conserved from cephalochordates to humans". Mobile DNA. 4 (1): 23. doi: 10.1186/1759-8753-4-23 . PMC   3902484 . PMID   24180413.
8. Henssen AG, Henaff E, Jiang E, Eisenberg AR, Carson JR, Villasante CM, Ray M, Still E, Burns M, Gandara J, Feschotte C, Mason CE, Kentsis A (September 2015). "Genomic DNA transposition induced by human PGBD5". eLife. 4. doi: 10.7554/eLife.10565 . PMC   4625184 . PMID   26406119.
9. Henssen AG, Koche R, Zhuang J, Jiang E, Reed C, Eisenberg A, Still E, MacArthur IC, Rodríguez-Fos E, Gonzalez S, Puiggròs M, Blackford AN, Mason CE, de Stanchina E, Gönen M, Emde AK, Shah M, Arora K, Reeves C, Socci ND, Perlman E, Antonescu CR, Roberts CW, Steen H, Mullen E, Jackson SP, Torrents D, Weng Z, Armstrong SA, Kentsis A (July 2017). "PGBD5 promotes site-specific oncogenic mutations in human tumors". Nature Genetics. 49 (7): 1005–1014. doi:10.1038/ng.3866. PMC   5489359 . PMID   28504702.
10. Ivics, Zoltán (May 2016). "Endogenous Transposase Source in Human Cells Mobilizes piggyBac Transposons". Molecular Therapy. 24 (5): 851–854. doi:10.1038/mt.2016.76. PMC   4881781 . PMID   27198853.
11. Shao, Benjamin (May 2018). Effects of PiggyBac Transposable Element Derived 5 (PGBD5) in Cortical Tissue (BS thesis). University of Connecticut.
12. Research, American Association for Cancer (2018-01-01). "The DNA Transposase PGBD5 Sensitizes Tumors to Inhibition of DNA Repair". Cancer Discovery. 8 (1): OF17. doi:10.1158/2159-8290.CD-RW2017-213. ISSN   2159-8274. PMID   29127084.
13. Vastrad, Basavaraj; Vastrad, Chanabasayya; Kotturshetti, Iranna (2020-12-24). "Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses". medRxiv   10.1101/2020.12.21.20248688v1 .
14. Broce, Iris; Karch, Celeste M.; Wen, Natalie; Fan, Chun C.; Wang, Yunpeng; Tan, Chin Hong; Kouri, Naomi; Ross, Owen A.; Höglinger, Günter U.; Muller, Ulrich; Hardy, John (2018-01-09). "Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies". PLOS Medicine. 15 (1): e1002487. doi: 10.1371/journal.pmed.1002487 . ISSN   1549-1676. PMC   5760014 . PMID   29315334.