PGBD5_HUMAN
ID PGBD5_HUMAN Reviewed; 524 AA.
AC Q8N414; A0A0A0MS21; A0PJF3; B4DM72; B7Z9K3; B9EK58; Q5SR37; Q6PJN2; U3REJ1;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2017, sequence version 4.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=PiggyBac transposable element-derived protein 5;
DE EC=3.1.-.-;
DE AltName: Full=PiggyBac domain-related protein 5 {ECO:0000303|PubMed:24180413};
DE AltName: Full=PiggyBac transposase 5 {ECO:0000303|PubMed:26406119};
GN Name=PGBD5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain, Lung carcinoma, and Oligodendroglioma;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 68-524 (ISOFORM 1), SUBCELLULAR LOCATION, AND
RP MISCELLANEOUS.
RC TISSUE=Blastocyst;
RX PubMed=24180413; DOI=10.1186/1759-8753-4-23;
RA Pavelitz T., Gray L.T., Padilla S.L., Bailey A.D., Weiner A.M.;
RT "PGBD5: a neural-specific intron-containing piggyBac transposase
RT domesticated over 500 million years ago and conserved from cephalochordates
RT to humans.";
RL Mob. DNA 4:23-23(2013).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 325-524.
RC TISSUE=Amygdala, and Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF ASP-237; ASP-244; GLU-257; ASP-261; ASP-263;
RP GLU-272; GLU-274; GLU-305; ASP-310; ASP-313; GLU-353; GLU-354; GLU-356;
RP ASP-372; GLU-434; GLU-442; ASP-455; ASP-456; ASP-494; GLU-508; GLU-513;
RP GLU-518 AND ASP-519.
RX PubMed=26406119; DOI=10.7554/elife.10565;
RA Henssen A.G., Henaff E., Jiang E., Eisenberg A.R., Carson J.R.,
RA Villasante C.M., Ray M., Still E., Burns M., Gandara J., Feschotte C.,
RA Mason C.E., Kentsis A.;
RT "Genomic DNA transposition induced by human PGBD5.";
RL Elife 4:0-0(2015).
RN [7]
RP FUNCTION.
RX PubMed=27491780; DOI=10.1186/s12864-016-2877-x;
RA Henssen A.G., Jiang E., Zhuang J., Pinello L., Socci N.D., Koche R.,
RA Gonen M., Villasante C.M., Armstrong S.A., Bauer D.E., Weng Z., Kentsis A.;
RT "Forward genetic screen of human transposase genomic rearrangements.";
RL BMC Genomics 17:548-548(2016).
RN [8]
RP FUNCTION, MUTAGENESIS OF ASP-237; ASP-263; GLU-434; GLU-442 AND ASP-455,
RP AND INVOLVEMENT IN RHABDOID TUMORS.
RX PubMed=28504702; DOI=10.1038/ng.3866;
RA Henssen A.G., Koche R., Zhuang J., Jiang E., Reed C., Eisenberg A.,
RA Still E., MacArthur I.C., Rodriguez-Fos E., Gonzalez S., Puiggros M.,
RA Blackford A.N., Mason C.E., de Stanchina E., Goenen M., Emde A.K., Shah M.,
RA Arora K., Reeves C., Socci N.D., Perlman E., Antonescu C.R.,
RA Roberts C.W.M., Steen H., Mullen E., Jackson S.P., Torrents D., Weng Z.,
RA Armstrong S.A., Kentsis A.;
RT "PGBD5 promotes site-specific oncogenic mutations in human tumors.";
RL Nat. Genet. 49:1005-1014(2017).
CC -!- FUNCTION: Transposase that mediates sequence-specific genomic
CC rearrangements (PubMed:26406119, PubMed:28504702). Can induce genomic
CC rearrangements that inactivate the HPRT1 gene (PubMed:27491780).
CC {ECO:0000269|PubMed:26406119, ECO:0000269|PubMed:27491780,
CC ECO:0000269|PubMed:28504702}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24180413}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8N414-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N414-2; Sequence=VSP_059131;
CC -!- DISEASE: Note=Induces site-specific DNA rearrangements, including
CC intrachromosomal deletions, as well as inversions, duplications and
CC translocations, in rhabdoid tumors that share developmental origin with
CC cells that normally express PGBD5, even though these tumors may not
CC exhibit apparent widespread genomic instability. This activity
CC recurrently targets regulatory elements and tumor suppressor genes and
CC promotes cell transformation. {ECO:0000269|PubMed:28504702}.
CC -!- MISCELLANEOUS: Has been domesticated very early in vertebrate
CC evolution, approximately 500 million years ago, in the common ancestor
CC of cephalochordates and vertebrates. {ECO:0000305|PubMed:24180413}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAG59784.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAH14339.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AL691479; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL133516; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC013901; AAH13901.1; -; mRNA.
DR EMBL; BC027466; AAH27466.1; -; mRNA.
DR EMBL; BC036865; AAH36865.1; -; mRNA.
DR EMBL; BC150638; AAI50639.1; -; mRNA.
DR EMBL; KF670820; AGX00581.1; -; mRNA.
DR EMBL; AK297321; BAG59784.1; ALT_INIT; mRNA.
DR EMBL; AK315968; BAH14339.1; ALT_INIT; mRNA.
DR CCDS; CCDS81430.1; -. [Q8N414-1]
DR RefSeq; NP_001245240.1; NM_001258311.1. [Q8N414-1]
DR AlphaFoldDB; Q8N414; -.
DR SMR; Q8N414; -.
DR BioGRID; 122741; 5.
DR IntAct; Q8N414; 1.
DR STRING; 9606.ENSP00000431404; -.
DR iPTMnet; Q8N414; -.
DR PhosphoSitePlus; Q8N414; -.
DR BioMuta; PGBD5; -.
DR DMDM; 300669682; -.
DR EPD; Q8N414; -.
DR MassIVE; Q8N414; -.
DR MaxQB; Q8N414; -.
DR PaxDb; Q8N414; -.
DR PeptideAtlas; Q8N414; -.
DR PRIDE; Q8N414; -.
DR ProteomicsDB; 71865; -.
DR Antibodypedia; 54100; 36 antibodies from 12 providers.
DR DNASU; 79605; -.
DR Ensembl; ENST00000391860.7; ENSP00000375733.2; ENSG00000177614.11. [Q8N414-1]
DR Ensembl; ENST00000525115.1; ENSP00000431404.1; ENSG00000177614.11. [Q8N414-2]
DR GeneID; 79605; -.
DR KEGG; hsa:79605; -.
DR MANE-Select; ENST00000391860.7; ENSP00000375733.2; NM_001258311.2; NP_001245240.1.
DR UCSC; uc057qgx.1; human. [Q8N414-1]
DR CTD; 79605; -.
DR DisGeNET; 79605; -.
DR GeneCards; PGBD5; -.
DR HGNC; HGNC:19405; PGBD5.
DR HPA; ENSG00000177614; Tissue enhanced (brain, pancreas).
DR MIM; 616791; gene.
DR neXtProt; NX_Q8N414; -.
DR OpenTargets; ENSG00000177614; -.
DR PharmGKB; PA134905621; -.
DR VEuPathDB; HostDB:ENSG00000177614; -.
DR eggNOG; ENOG502QT9F; Eukaryota.
DR GeneTree; ENSGT00510000047893; -.
DR InParanoid; Q8N414; -.
DR OMA; SEAYHVT; -.
DR OrthoDB; 1139412at2759; -.
DR PhylomeDB; Q8N414; -.
DR TreeFam; TF332005; -.
DR PathwayCommons; Q8N414; -.
DR SignaLink; Q8N414; -.
DR BioGRID-ORCS; 79605; 3 hits in 256 CRISPR screens.
DR ChiTaRS; PGBD5; human.
DR GenomeRNAi; 79605; -.
DR Pharos; Q8N414; Tdark.
DR PRO; PR:Q8N414; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8N414; protein.
DR Bgee; ENSG00000177614; Expressed in frontal pole and 147 other tissues.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0004803; F:transposase activity; IDA:UniProtKB.
DR GO; GO:0098038; P:non-replicative transposition, DNA-mediated; IMP:UniProtKB.
DR InterPro; IPR029526; PGBD.
DR InterPro; IPR042423; PGBD5.
DR PANTHER; PTHR28576; PTHR28576; 1.
DR Pfam; PF13843; DDE_Tnp_1_7; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Chromosomal rearrangement; Endonuclease; Hydrolase;
KW Nuclease; Nucleus; Phosphoprotein; Reference proteome; Transposition.
FT CHAIN 1..524
FT /note="PiggyBac transposable element-derived protein 5"
FT /id="PRO_0000288056"
FT REGION 30..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 41..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 521
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:D3YZI9"
FT VAR_SEQ 1..110
FT /note="MAEGGGGARRRAPALLEAARARYESLHISDDVFGESGPDSGGNPFYSTSAAS
FT RSSSAASSDDEREPPGPPGAAPPPPRAPDAQEPEEDEAGAGWSAALRDRPPPRFEDTG
FT -> MPDYRTRALFVQSTLGDSAGPELQLLSIVPGRDLQPSDSFT (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_059131"
FT MUTAGEN 237
FT /note="D->A: Loss of DNA transposase activity and of cell
FT transforming activity."
FT /evidence="ECO:0000269|PubMed:26406119,
FT ECO:0000269|PubMed:28504702"
FT MUTAGEN 244
FT /note="D->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 257
FT /note="E->A: Decreased DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 261
FT /note="D->A: Decreased DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 263
FT /note="D->A: Loss of DNA transposase activity and of cell
FT transforming activity."
FT /evidence="ECO:0000269|PubMed:26406119,
FT ECO:0000269|PubMed:28504702"
FT MUTAGEN 272
FT /note="E->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 274
FT /note="E->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 305
FT /note="E->A: Decreased DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 310
FT /note="D->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 313
FT /note="D->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 353
FT /note="E->A: Decreased DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 354
FT /note="E->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 356
FT /note="E->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 372
FT /note="D->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 434
FT /note="E->A: No effect on DNA transposase activity, nor on
FT cell transforming activity."
FT /evidence="ECO:0000269|PubMed:26406119,
FT ECO:0000269|PubMed:28504702"
FT MUTAGEN 442
FT /note="E->A: No effect on DNA transposase activity, nor on
FT cell transforming activity."
FT /evidence="ECO:0000269|PubMed:26406119,
FT ECO:0000269|PubMed:28504702"
FT MUTAGEN 455
FT /note="D->A: Loss of DNA transposase activity. No effect on
FT cell transforming activity."
FT /evidence="ECO:0000269|PubMed:26406119,
FT ECO:0000269|PubMed:28504702"
FT MUTAGEN 456
FT /note="D->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 494
FT /note="D->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 508
FT /note="E->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 513
FT /note="E->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 518
FT /note="E->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT MUTAGEN 519
FT /note="D->A: No effect on DNA transposase activity."
FT /evidence="ECO:0000269|PubMed:26406119"
FT CONFLICT 314
FT /note="A -> V (in Ref. 2; AAI50639)"
FT /evidence="ECO:0000305"
FT CONFLICT 411
FT /note="H -> Y (in Ref. 4; BAG59784)"
FT /evidence="ECO:0000305"
FT CONFLICT 469
FT /note="K -> Q (in Ref. 4; BAH14339)"
FT /evidence="ECO:0000305"
SQ 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
