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PiggyBac transposable element-derived protein 5 (EC 3.1.-.-) (PiggyBac domain-related protein 5) (PiggyBac transposase 5)

 PGBD5_HUMAN             Reviewed;         524 AA.
Q8N414; A0A0A0MS21; A0PJF3; B4DM72; B7Z9K3; B9EK58; Q5SR37; Q6PJN2;
U3REJ1;
29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
25-OCT-2017, sequence version 4.
07-NOV-2018, entry version 97.
RecName: Full=PiggyBac transposable element-derived protein 5;
EC=3.1.-.-;
AltName: Full=PiggyBac domain-related protein 5 {ECO:0000303|PubMed:24180413};
AltName: Full=PiggyBac transposase 5 {ECO:0000303|PubMed:26406119};
Name=PGBD5;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16710414; DOI=10.1038/nature04727;
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Brain, Lung carcinoma, and Oligodendroglioma;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
NUCLEOTIDE SEQUENCE [MRNA] OF 68-524 (ISOFORM 1), SUBCELLULAR
LOCATION, AND MISCELLANEOUS.
TISSUE=Blastocyst;
PubMed=24180413; DOI=10.1186/1759-8753-4-23;
Pavelitz T., Gray L.T., Padilla S.L., Bailey A.D., Weiner A.M.;
"PGBD5: a neural-specific intron-containing piggyBac transposase
domesticated over 500 million years ago and conserved from
cephalochordates to humans.";
Mob. DNA 4:23-23(2013).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 325-524.
TISSUE=Amygdala, and Brain;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[5]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[6]
FUNCTION, AND MUTAGENESIS OF ASP-237; ASP-244; GLU-257; ASP-261;
ASP-263; GLU-272; GLU-274; GLU-305; ASP-310; ASP-313; GLU-353;
GLU-354; GLU-356; ASP-372; GLU-434; GLU-442; ASP-455; ASP-456;
ASP-494; GLU-508; GLU-513; GLU-518 AND ASP-519.
PubMed=26406119; DOI=10.7554/eLife.10565;
Henssen A.G., Henaff E., Jiang E., Eisenberg A.R., Carson J.R.,
Villasante C.M., Ray M., Still E., Burns M., Gandara J., Feschotte C.,
Mason C.E., Kentsis A.;
"Genomic DNA transposition induced by human PGBD5.";
Elife 4:0-0(2015).
[7]
FUNCTION.
PubMed=27491780; DOI=10.1186/s12864-016-2877-x;
Henssen A.G., Jiang E., Zhuang J., Pinello L., Socci N.D., Koche R.,
Gonen M., Villasante C.M., Armstrong S.A., Bauer D.E., Weng Z.,
Kentsis A.;
"Forward genetic screen of human transposase genomic rearrangements.";
BMC Genomics 17:548-548(2016).
[8]
FUNCTION, MUTAGENESIS OF ASP-237; ASP-263; GLU-434; GLU-442 AND
ASP-455, AND INVOLVEMENT IN RHABDOID TUMORS.
PubMed=28504702; DOI=10.1038/ng.3866;
Henssen A.G., Koche R., Zhuang J., Jiang E., Reed C., Eisenberg A.,
Still E., MacArthur I.C., Rodriguez-Fos E., Gonzalez S., Puiggros M.,
Blackford A.N., Mason C.E., de Stanchina E., Goenen M., Emde A.K.,
Shah M., Arora K., Reeves C., Socci N.D., Perlman E., Antonescu C.R.,
Roberts C.W.M., Steen H., Mullen E., Jackson S.P., Torrents D.,
Weng Z., Armstrong S.A., Kentsis A.;
"PGBD5 promotes site-specific oncogenic mutations in human tumors.";
Nat. Genet. 49:1005-1014(2017).
-!- FUNCTION: Transposase that mediates sequence-specific genomic
rearrangements (PubMed:26406119, PubMed:28504702). Can induce
genomic rearrangements that inactivate the HPRT1 gene
(PubMed:27491780). {ECO:0000269|PubMed:26406119,
ECO:0000269|PubMed:27491780, ECO:0000269|PubMed:28504702}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24180413}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q8N414-1; Sequence=Displayed;
Name=2;
IsoId=Q8N414-2; Sequence=VSP_059131;
Note=No experimental confirmation available.
{ECO:0000305|PubMed:15489334};
-!- DISEASE: Note=Induces site-specific DNA rearrangements, including
intrachromosomal deletions, as well as inversions, duplications
and translocations, in rhabdoid tumors that share developmental
origin with cells that normally express PGBD5, even though these
tumors may not exhibit apparent widespread genomic instability.
This activity recurrently targets regulatory elements and tumor
suppressor genes and promotes cell transformation.
{ECO:0000269|PubMed:28504702}.
-!- MISCELLANEOUS: Has been domesticated very early in vertebrate
evolution, approximately 500 million years ago, in the common
ancestor of cephalochordates and vertebrates.
{ECO:0000305|PubMed:24180413}.
-!- SEQUENCE CAUTION:
Sequence=BAG59784.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
Sequence=BAH14339.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
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EMBL; AL691479; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; AL133516; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC013901; AAH13901.1; -; mRNA.
EMBL; BC027466; AAH27466.1; -; mRNA.
EMBL; BC036865; AAH36865.1; -; mRNA.
EMBL; BC150638; AAI50639.1; -; mRNA.
EMBL; KF670820; AGX00581.1; -; mRNA.
EMBL; AK297321; BAG59784.1; ALT_INIT; mRNA.
EMBL; AK315968; BAH14339.1; ALT_INIT; mRNA.
CCDS; CCDS81430.1; -. [Q8N414-1]
RefSeq; NP_001245240.1; NM_001258311.1. [Q8N414-1]
UniGene; Hs.520463; -.
ProteinModelPortal; Q8N414; -.
BioGrid; 122741; 1.
STRING; 9606.ENSP00000322530; -.
iPTMnet; Q8N414; -.
PhosphoSitePlus; Q8N414; -.
BioMuta; PGBD5; -.
DMDM; 300669682; -.
EPD; Q8N414; -.
PaxDb; Q8N414; -.
PeptideAtlas; Q8N414; -.
PRIDE; Q8N414; -.
ProteomicsDB; 71865; -.
Ensembl; ENST00000391860; ENSP00000375733; ENSG00000177614. [Q8N414-1]
Ensembl; ENST00000525115; ENSP00000431404; ENSG00000177614. [Q8N414-2]
GeneID; 79605; -.
KEGG; hsa:79605; -.
UCSC; uc057qgx.1; human. [Q8N414-1]
CTD; 79605; -.
EuPathDB; HostDB:ENSG00000177614.9; -.
GeneCards; PGBD5; -.
HGNC; HGNC:19405; PGBD5.
HPA; HPA065010; -.
MIM; 616791; gene.
neXtProt; NX_Q8N414; -.
OpenTargets; ENSG00000177614; -.
PharmGKB; PA134905621; -.
eggNOG; ENOG410IJ9Y; Eukaryota.
eggNOG; ENOG410XP35; LUCA.
GeneTree; ENSGT00510000047893; -.
HOGENOM; HOG000115519; -.
HOVERGEN; HBG053995; -.
InParanoid; Q8N414; -.
OMA; MDFFQLF; -.
OrthoDB; EOG091G0684; -.
PhylomeDB; Q8N414; -.
TreeFam; TF332005; -.
ChiTaRS; PGBD5; human.
GenomeRNAi; 79605; -.
PRO; PR:Q8N414; -.
Proteomes; UP000005640; Chromosome 1.
Bgee; ENSG00000177614; Expressed in 168 organ(s), highest expression level in entorhinal cortex.
CleanEx; HS_PGBD5; -.
GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
GO; GO:0032196; P:transposition; IEA:UniProtKB-KW.
InterPro; IPR029526; PGBD.
Pfam; PF13843; DDE_Tnp_1_7; 1.
1: Evidence at protein level;
Alternative splicing; Chromosomal rearrangement; Complete proteome;
Endonuclease; Hydrolase; Nuclease; Nucleus; Phosphoprotein;
Reference proteome; Transposition.
CHAIN 1 524 PiggyBac transposable element-derived
protein 5.
/FTId=PRO_0000288056.
MOD_RES 521 521 Phosphoserine.
{ECO:0000250|UniProtKB:D3YZI9}.
VAR_SEQ 1 110 MAEGGGGARRRAPALLEAARARYESLHISDDVFGESGPDSG
GNPFYSTSAASRSSSAASSDDEREPPGPPGAAPPPPRAPDA
QEPEEDEAGAGWSAALRDRPPPRFEDTG -> MPDYRTRAL
FVQSTLGDSAGPELQLLSIVPGRDLQPSDSFT (in
isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_059131.
MUTAGEN 237 237 D->A: Loss of DNA transposase activity
and of cell transforming activity.
{ECO:0000269|PubMed:26406119,
ECO:0000269|PubMed:28504702}.
MUTAGEN 244 244 D->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 257 257 E->A: Decreased DNA transposase activity.
{ECO:0000269|PubMed:26406119}.
MUTAGEN 261 261 D->A: Decreased DNA transposase activity.
{ECO:0000269|PubMed:26406119}.
MUTAGEN 263 263 D->A: Loss of DNA transposase activity
and of cell transforming activity.
{ECO:0000269|PubMed:26406119,
ECO:0000269|PubMed:28504702}.
MUTAGEN 272 272 E->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 274 274 E->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 305 305 E->A: Decreased DNA transposase activity.
{ECO:0000269|PubMed:26406119}.
MUTAGEN 310 310 D->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 313 313 D->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 353 353 E->A: Decreased DNA transposase activity.
{ECO:0000269|PubMed:26406119}.
MUTAGEN 354 354 E->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 356 356 E->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 372 372 D->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 434 434 E->A: No effect on DNA transposase
activity, nor on cell transforming
activity. {ECO:0000269|PubMed:26406119,
ECO:0000269|PubMed:28504702}.
MUTAGEN 442 442 E->A: No effect on DNA transposase
activity, nor on cell transforming
activity. {ECO:0000269|PubMed:26406119,
ECO:0000269|PubMed:28504702}.
MUTAGEN 455 455 D->A: Loss of DNA transposase activity.
No effect on cell transforming activity.
{ECO:0000269|PubMed:26406119,
ECO:0000269|PubMed:28504702}.
MUTAGEN 456 456 D->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 494 494 D->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 508 508 E->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 513 513 E->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 518 518 E->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
MUTAGEN 519 519 D->A: No effect on DNA transposase
activity. {ECO:0000269|PubMed:26406119}.
CONFLICT 314 314 A -> V (in Ref. 2; AAI50639).
{ECO:0000305}.
CONFLICT 411 411 H -> Y (in Ref. 4; BAG59784).
{ECO:0000305}.
CONFLICT 469 469 K -> Q (in Ref. 4; BAH14339).
{ECO:0000305}.
SEQUENCE 524 AA; 58464 MW; 049D3B3D983B295B CRC64;
MAEGGGGARR RAPALLEAAR ARYESLHISD DVFGESGPDS GGNPFYSTSA ASRSSSAASS
DDEREPPGPP GAAPPPPRAP DAQEPEEDEA GAGWSAALRD RPPPRFEDTG GPTRKMPPSA
SAVDFFQLFV PDNVLKNMVV QTNMYAKKFQ ERFGSDGAWV EVTLTEMKAF LGYMISTSIS
HCESVLSIWS GGFYSNRSLA LVMSQARFEK ILKYFHVVAF RSSQTTHGLY KVQPFLDSLQ
NSFDSAFRPS QTQVLHEPLI DEDPVFIATC TERELRKRKK RKFSLWVRQC SSTGFIIQIY
VHLKEGGGPD GLDALKNKPQ LHSMVARSLC RNAAGKNYII FTGPSITSLT LFEEFEKQGI
YCCGLLRARK SDCTGLPLSM LTNPATPPAR GQYQIKMKGN MSLICWYNKG HFRFLTNAYS
PVQQGVIIKR KSGEIPCPLA VEAFAAHLSY ICRYDDKYSK YFISHKPNKT WQQVFWFAIS
IAINNAYILY KMSDAYHVKR YSRAQFGERL VRELLGLEDA SPTH


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