PiggyBac Transposable Element Derived 5
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{infobox_gene}}
PiggyBac Transposable Element Derived 5 is an enzyme that in humans is encoded by the PGBD5 gene.{{cite web|title=PGBD5 piggyBac transposable element derived 5 [Homo sapiens (human)] - Gene - NCBI|url=https://www.ncbi.nlm.nih.gov/gene/79605|website=www.ncbi.nlm.nih.gov|access-date=8 April 2017}} PGBD5 is a DNA transposase related to the ancient PiggyBac transposase first identified in the cabbage looper moth, Trichoplusia ni.{{cite journal | vauthors = Toman J | title = A course to pursue | journal = Nursing Times| year = 1979 | volume = 75 | issue = 17 | pages = 694–695 |pmid= 255260}} The gene is believed to have been domesticated over 500 million years ago in the common ancestor of cephalochordates and vertebrates.{{cite journal | vauthors = Pavelitz T, Gray LT, Padilla SL, Bailey AD, Weiner AM | title = PGBD5: a neural-specific intron-containing piggyBac transposase domesticated over 500 million years ago and conserved from cephalochordates to humans | journal = Mobile DNA | volume = 4 | issue = 1 | pages = 23 | date = November 2013 | pmid = 24180413 | doi = 10.1186/1759-8753-4-23 | pmc = 3902484 | doi-access = free }} The putative catalytic triad of the protein composed of three aspartic acid residues is conserved among PGBD5-like genes through evolution, and is distinct from other PiggyBac-like genes. PGBD5 has been shown to be able to transpose DNA in a sequence-specific, cut-and-paste fashion.{{cite journal | vauthors = 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 | title = Genomic DNA transposition induced by human PGBD5 | journal = eLife | volume = 4 | date = September 2015 | pmid = 26406119 | doi = 10.7554/eLife.10565 | pmc = 4625184 | doi-access = free }} PGBD5 has also been proposed to mediate site-specific DNA rearrangements in human tumors.{{cite journal | vauthors = 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 | title = PGBD5 promotes site-specific oncogenic mutations in human tumors | journal = Nature Genetics | volume = 49 | issue = 7 | pages = 1005–1014 | date = July 2017 | pmid = 28504702 | pmc = 5489359 | doi = 10.1038/ng.3866 }}
Human PGBD5 can mobilize the insect PiggyBac transposons in human cell culture.{{Cite journal|last=Ivics|first=Zoltán|date=May 2016|title=Endogenous Transposase Source in Human Cells Mobilizes piggyBac Transposons|journal=Molecular Therapy|language=en|volume=24|issue=5|pages=851–854|doi=10.1038/mt.2016.76|pmc=4881781|pmid=27198853}}
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.{{Cite thesis|last=Shao|first=Benjamin|date=May 2018|title=Effects of PiggyBac Transposable Element Derived 5 (PGBD5) in Cortical Tissue|type=BS thesis|publisher=University of Connecticut|url=https://opencommons.uconn.edu/srhonors_theses/593}}{{better source needed|date=March 2023}}
Disease Associations
PGBD5 is expressed in the majority of human pediatric solid tumors.{{Cite journal|last=Research|first=American Association for Cancer|date=2018-01-01|title=The DNA Transposase PGBD5 Sensitizes Tumors to Inhibition of DNA Repair|url=https://cancerdiscovery.aacrjournals.org/content/8/1/OF17|journal=Cancer Discovery|language=en|volume=8|issue=1|pages=OF17|doi=10.1158/2159-8290.CD-RW2017-213|issn=2159-8274|pmid=29127084|doi-access=|url-access=subscription}} It's upregulated in sporadic Creutzfeldt-Jakob disease.{{Cite medRxiv |last1=Vastrad |first1=Basavaraj |last2=Vastrad |first2=Chanabasayya |last3=Kotturshetti |first3=Iranna |date=2020-12-24 |title=Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses |language=en |medrxiv=10.1101/2020.12.21.20248688v1}} 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.{{Cite journal|last1=Broce|first1=Iris|last2=Karch|first2=Celeste M.|last3=Wen|first3=Natalie|last4=Fan|first4=Chun C.|last5=Wang|first5=Yunpeng|last6=Tan|first6=Chin Hong|last7=Kouri|first7=Naomi|last8=Ross|first8=Owen A.|last9=Höglinger|first9=Günter U.|last10=Muller|first10=Ulrich|last11=Hardy|first11=John|date=2018-01-09|title=Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies|journal=PLOS Medicine|language=en|volume=15|issue=1|pages=e1002487|doi=10.1371/journal.pmed.1002487|issn=1549-1676|pmc=5760014|pmid=29315334 |doi-access=free }}