PLAG1_MOUSE
ID PLAG1_MOUSE Reviewed; 499 AA.
AC Q9QYE0; B1AXC4; Q3UXC0;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Zinc finger protein PLAG1;
DE AltName: Full=Pleiomorphic adenoma gene 1 protein;
GN Name=Plag1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/SvEv; TISSUE=Embryo;
RX PubMed=15585652; DOI=10.1182/blood-2004-09-3630;
RA Landrette S.F., Kuo Y.H., Hensen K., van Doorn-Khosrovani S.B.,
RA Perrat P.N., Van de Ven W.J., Delwel R., Castilla L.H.;
RT "Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in
RT cooperation with Cbfb-MYH11.";
RL Blood 105:2900-2907(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/Sv;
RA Hensen K., Voz M.L., Van de Ven W.J.M., Kas K.;
RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 324-499.
RC STRAIN=C57BL/6J; TISSUE=Egg;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [7]
RP DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=15606491; DOI=10.1111/j.1440-169x.2004.00762.x;
RA Hensen K., Braem C., Declercq J., Van Dyck F., Dewerchin M., Fiette L.,
RA Denef C., Van de Ven W.J.M.;
RT "Targeted disruption of the murine Plag1 proto-oncogene causes growth
RT retardation and reduced fertility.";
RL Dev. Growth Differ. 46:459-470(2004).
RN [8]
RP FUNCTION, AND COOPERATION WITH CBFB-MYH11.
RX PubMed=15044690; DOI=10.1073/pnas.0400930101;
RA Castilla L.H., Perrat P., Martinez N.J., Landrette S.F., Keys R.,
RA Oikemus S., Flanegan J., Heilman S., Garrett L., Dutra A., Anderson S.,
RA Pihan G.A., Wolff L., Liu P.P.;
RT "Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis
RT of acute myeloid leukemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4924-4929(2004).
RN [9]
RP TRANSGENIC MICE, AND FUNCTION.
RX PubMed=15930271; DOI=10.1158/0008-5472.can-04-4041;
RA Declercq J., Van Dyck F., Braem C.V., Van Valckenborgh I.C., Voz M.,
RA Wassef M., Schoonjans L., Van Damme B., Fiette L., Van de Ven W.J.M.;
RT "Salivary gland tumors in transgenic mice with targeted PLAG1 proto-
RT oncogene overexpression.";
RL Cancer Res. 65:4544-4553(2005).
RN [10]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16193498; DOI=10.1002/dvdy.20577;
RA Alam S., Zinyk D., Ma L., Schuurmans C.;
RT "Members of the Plag gene family are expressed in complementary and
RT overlapping regions in the developing murine nervous system.";
RL Dev. Dyn. 234:772-782(2005).
RN [11]
RP TRANSGENIC MICE, AND FUNCTION.
RX PubMed=16108035; DOI=10.1002/ijc.21400;
RA Zhao X., Ren W., Yang W., Wang Y., Kong H., Wang L., Yan L., Xu G., Fei J.,
RA Fu J., Zhang C., Wang Z.;
RT "Wnt pathway is involved in pleomorphic adenomas induced by overexpression
RT of PLAG1 in transgenic mice.";
RL Int. J. Cancer 118:643-648(2006).
CC -!- FUNCTION: Transcription factor whose activation results in up-
CC regulation of target genes, such as IGFII, leading to uncontrolled cell
CC proliferation: when overexpressed in cultured cells, higher
CC proliferation rate and transformation are observed. Other target genes
CC such as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with
CC PLAG1 induction. Proto-oncogene whose ectopic expression can trigger
CC the development of pleomorphic adenomas of the salivary gland and
CC lipoblastomas. Cooperates with CBFB-MYH11.
CC {ECO:0000269|PubMed:15044690, ECO:0000269|PubMed:15930271,
CC ECO:0000269|PubMed:16108035}.
CC -!- SUBUNIT: Interacts with KPNA2, which escorts protein to the nucleus via
CC interaction with nuclear localization signal. Interacts with E3 SUMO-
CC protein ligase PIAS1, PIAS2 and PIAS4 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Strong nucleolar localization when
CC sumoylation is inhibited. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in heart, spleen, lung, kidney, brain,
CC testis and epididymis but not in salivary glands.
CC {ECO:0000269|PubMed:16193498}.
CC -!- DEVELOPMENTAL STAGE: High fetal expression with a strong decline after
CC birth. Expressed at 9.5 dpc and 10.5 dpc in nervous system with highest
CC level in telencephalon, diencephalon, and midbrain, as well as
CC regionalized expression in the neural tube, which is characteristic of
CC genes involved in the specification of neuronal fates.
CC {ECO:0000269|PubMed:15606491, ECO:0000269|PubMed:16193498}.
CC -!- DOMAIN: C2H2-type zinc fingers 3 interacts with DNA-binding site G-
CC clusterinc fingers. C2H2-type zinc fingers 6 and 7 interact with DNA-
CC binding site core sequence (By similarity). {ECO:0000250}.
CC -!- PTM: Sumoylated with SUMO1; which inhibits transcriptional activity,
CC but does not affect nuclear localization. Blockers of sumoylation
CC pathway such as SENP3 and inactive UBE2I increases transcriptional
CC capacity. Sumoylation is increased in the presence of PIAS1 (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Acetylated by lysine acetyltransferase EP300; which activates
CC transcriptional capacity. Lysine residues that are sumoylated also seem
CC to be target for acetylation (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit growth retardation with lower birth
CC weight and disproportionally small seminal vesicles and ventral
CC prostate as well as decreased fertility in both male and female.
CC However, IGFII expression is normal in embryos.
CC {ECO:0000269|PubMed:15606491}.
CC -!- MISCELLANEOUS: Mice overexpressing Plag1 develop normally with high
CC Plag1 transgene expression in salivary glands, spleen and weak mammary
CC gland detection. They develop salivary gland tumors with major
CC pathological features of human pleimorphic adenomas at the age of 1-5
CC months.
CC -!- MISCELLANEOUS: Mice with Plag1 overexpression targeted to salivary and
CC mammary gland develop multifocal salivary gland tumors with
CC pathological features of human pleimorphic adenomas at the age of 5
CC weeks, as well as mammary gland tumors at the age of 1 year. Plag1
CC overexpression in salivary gland are accompanied by increased IGFII
CC expression. Besides features characteristic of benign pleimorphic
CC adenomas, malignant characteristics are also observed in salivary gland
CC tumors as well as metastasis to the lungs, reinforcing the tumorigenic
CC role of Plag1.
CC -!- MISCELLANEOUS: Neonate mice carrying a human myeloid leukemia
CC translocation-associated fusion gene CBFB-MYH11, injected with a
CC retrovirus (4070A), develop the pathology within 2-5 months due to few
CC viral insertions in some genes, such as PLAG1. Insertions near the
CC transcription start site of PLAG1 are predominant in the related tumors
CC and probably participate in the transformation process. Plag1 is one
CC candidate gene that can cooperate with CBFB-MYH11 for leukemogenesis in
CC this mouse model.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAE22643.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY574219; AAS86161.1; -; mRNA.
DR EMBL; AF057366; AAF21762.1; -; mRNA.
DR EMBL; BC139283; AAI39284.1; -; mRNA.
DR EMBL; BC139285; AAI39286.1; -; mRNA.
DR EMBL; AL807387; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466538; EDL05712.1; -; Genomic_DNA.
DR EMBL; AK135759; BAE22643.1; ALT_INIT; mRNA.
DR CCDS; CCDS17941.1; -.
DR RefSeq; NP_064353.2; NM_019969.3.
DR RefSeq; XP_006538179.1; XM_006538116.3.
DR RefSeq; XP_011248381.1; XM_011250079.2.
DR RefSeq; XP_017175819.1; XM_017320330.1.
DR RefSeq; XP_017175820.1; XM_017320331.1.
DR AlphaFoldDB; Q9QYE0; -.
DR SMR; Q9QYE0; -.
DR STRING; 10090.ENSMUSP00000003369; -.
DR PhosphoSitePlus; Q9QYE0; -.
DR MaxQB; Q9QYE0; -.
DR PaxDb; Q9QYE0; -.
DR PRIDE; Q9QYE0; -.
DR Antibodypedia; 1454; 259 antibodies from 26 providers.
DR DNASU; 56711; -.
DR Ensembl; ENSMUST00000003369; ENSMUSP00000003369; ENSMUSG00000003282.
DR GeneID; 56711; -.
DR KEGG; mmu:56711; -.
DR UCSC; uc008rwp.2; mouse.
DR CTD; 5324; -.
DR MGI; MGI:1891916; Plag1.
DR VEuPathDB; HostDB:ENSMUSG00000003282; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000159246; -.
DR HOGENOM; CLU_002678_66_1_1; -.
DR InParanoid; Q9QYE0; -.
DR OMA; GTENRHD; -.
DR OrthoDB; 615178at2759; -.
DR PhylomeDB; Q9QYE0; -.
DR TreeFam; TF332024; -.
DR BioGRID-ORCS; 56711; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Plag1; mouse.
DR PRO; PR:Q9QYE0; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9QYE0; protein.
DR Bgee; ENSMUSG00000003282; Expressed in animal zygote and 103 other tissues.
DR ExpressionAtlas; Q9QYE0; baseline and differential.
DR Genevisible; Q9QYE0; MM.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0022612; P:gland morphogenesis; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0035265; P:organ growth; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0060736; P:prostate gland growth; IMP:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR InterPro; IPR027765; PLAG1/PLAGL2.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR PANTHER; PTHR24390:SF64; PTHR24390:SF64; 1.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00355; ZnF_C2H2; 7.
DR SUPFAM; SSF57667; SSF57667; 4.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 7.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 7.
PE 2: Evidence at transcript level;
KW Acetylation; Activator; DNA-binding; Isopeptide bond; Metal-binding;
KW Nucleus; Proto-oncogene; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..499
FT /note="Zinc finger protein PLAG1"
FT /id="PRO_0000295108"
FT ZN_FING 34..56
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 62..86
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 92..114
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 121..143
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 150..172
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 185..207
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 213..236
FT /note="C2H2-type 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..84
FT /note="Interaction with KPNA2"
FT /evidence="ECO:0000250"
FT REGION 41..242
FT /note="Decreased nuclear import with localization in the
FT nucleus but also in the cytoplasm"
FT /evidence="ECO:0000250"
FT REGION 243..499
FT /note="Activates transcription; Inhibition of nuclear
FT import due to lack of NLS and KPNA2 interaction"
FT /evidence="ECO:0000250"
FT REGION 243..383
FT /note="Repression domain; contains 3 sumoylation motifs and
FT massively decrease transcription activity"
FT /evidence="ECO:0000250"
FT REGION 365..400
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 384..499
FT /note="Massively activates transcription"
FT /evidence="ECO:0000250"
FT MOTIF 22..25
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 365..385
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 244
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 263
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CONFLICT 433
FT /note="P -> T (in Ref. 1; AAS86161 and 2; AAF21762)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 499 AA; 55579 MW; A3493D2DADCB83B2 CRC64;
MATVIPGDLS EVRDTQKAPS GKRKRGESKP RKNFPCQLCD KAFNSVEKLK VHSFSHTGER
PYKCTHQDCT KAFVSKYKLQ RHMATHSPEK THKCNYCEKM FHRKDHLKNH LHTHDPNKET
FKCEECGKSY NTKLGFKRHL ALHAATSGDL TCKVCLQNFE STGVLLEHLK SHAGKSSGGV
KEKKHQCEHC ERRFYTRKDV RRHMVVHTGR KDFLCQYCAQ RFGRKDHLTR HMKKSHNQEL
LKVKTEPVDF LDPFTCNMSV PIKDELLPVM SLPSSELLSK PFTNTLQLNL YNTPFQSMQS
SGSAHQMITT LPLGMTCPID MDAVHPSHHL AFKCPFSSTS YAISIPEKEQ PLKGEIESYL
MELQGGAPSS SQDSPASSSK LGLEPQSGSP DDGAGDLSLS KSSISISDPL STPALDFSQL
FNFIPLNGPP YNPLSVGSLG MSYSQEEAHS SVSQLPTQTQ DLQDPANTVG LSSLHSLSAA
FTSSLSSSTT LPRFHQAFQ
