PLAG1_HUMAN
ID PLAG1_HUMAN Reviewed; 500 AA.
AC Q6DJT9; B4DLC2; Q59GH8; Q9Y4L2;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Zinc finger protein PLAG1;
DE AltName: Full=Pleiomorphic adenoma gene 1 protein;
GN Name=PLAG1;
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, CHROMOSOMAL
RP TRANSLOCATION WITH CTNNB1, AND VARIANT THR-458.
RX PubMed=9020842; DOI=10.1038/ng0297-170;
RA Kas K., Voz M.L., Roeijer E., Astroem A.-K., Meyen E., Stenman G.,
RA Van de Ven W.J.M.;
RT "Promoter swapping between the genes for a novel zinc finger protein and
RT beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12)
RT translocations.";
RL Nat. Genet. 15:170-174(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Tongue;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 TISSUE SPECIFICITY, AND MUTAGENESIS OF THR-339 AND SER-340.
RX PubMed=9722527; DOI=10.1074/jbc.273.36.23026;
RA Kas K., Voz M.L., Hensen K., Meyen E., Van de Ven W.J.M.;
RT "Transcriptional activation capacity of the novel PLAG family of zinc
RT finger proteins.";
RL J. Biol. Chem. 273:23026-23032(1998).
RN [7]
RP CHROMOSOMAL TRANSLOCATION WITH LIFR.
RX PubMed=9525740; DOI=10.1038/sj.onc.1201660;
RA Voz M.L., Astrom A.-K., Kas K., Mark J., Stenman G., Van de Ven W.J.M.;
RT "The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas
RT results in upregulation of PLAG1 gene expression under control of the LIFR
RT promoter.";
RL Oncogene 16:1409-1416(1998).
RN [8]
RP CHROMOSOMAL TRANSLOCATION WITH CTNNB1 AND TCEA1, AND TISSUE SPECIFICITY.
RX PubMed=10029085;
RA Astroem A.-K., Voz M.L., Kas K., Roeijer E., Wedell B., Mandahl N.,
RA Van de Ven W., Mark J., Stenman G.;
RT "Conserved mechanism of PLAG1 activation in salivary gland tumors with and
RT without chromosome 8q12 abnormalities: identification of SII as a new
RT fusion partner gene.";
RL Cancer Res. 59:918-923(1999).
RN [9]
RP SUBCELLULAR LOCATION, DNA-BINDING, AND MUTAGENESIS OF HIS-92 AND HIS-227.
RX PubMed=10646861;
RA Voz M.L., Agten N.S., Van de Ven W.J.M., Kas K.;
RT "PLAG1, the main translocation target in pleomorphic adenoma of the
RT salivary glands, is a positive regulator of IGF-II.";
RL Cancer Res. 60:106-113(2000).
RN [10]
RP CHROMOSOMAL REARRANGEMENT WITH HAS2 AND COL1A2.
RX PubMed=10987300;
RA Hibbard M.K., Kozakewich H.P., Dal Cin P., Sciot R., Tan X., Xiao S.,
RA Fletcher J.A.;
RT "PLAG1 fusion oncogenes in lipoblastoma.";
RL Cancer Res. 60:4869-4872(2000).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF HIS-227.
RX PubMed=11888928;
RA Hensen K., Van Valckenborgh I.C.C., Kas K., Van de Ven W.J.M., Voz M.L.;
RT "The tumorigenic diversity of the three PLAG family members is associated
RT with different DNA binding capacities.";
RL Cancer Res. 62:1510-1517(2002).
RN [12]
RP INTERACTION WITH KPNA2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 23-ARG-LYS-24 AND 31-ARG-LYS-32.
RX PubMed=11882654; DOI=10.1074/jbc.m112112200;
RA Braem C.V., Kas K., Meyen E., Debiec-Rychter M., Van De Ven W.J.M.,
RA Voz M.L.;
RT "Identification of a karyopherin alpha 2 recognition site in PLAG1, which
RT functions as a nuclear localization signal.";
RL J. Biol. Chem. 277:19673-19678(2002).
RN [13]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14695992; DOI=10.1002/gcc.10307;
RA Zatkova A., Rouillard J.-M., Hartmann W., Lamb B.J., Kuick R., Eckart M.,
RA von Schweinitz D., Koch A., Fonatsch C., Pietsch T., Hanash S.M.,
RA Wimmer K.;
RT "Amplification and overexpression of the IGF2 regulator PLAG1 in
RT hepatoblastoma.";
RL Genes Chromosomes Cancer 39:126-137(2004).
RN [14]
RP SUMOYLATION, MUTAGENESIS OF LYS-244; LYS-263 AND LYS-353, AND INTERACTION
RP WITH PIAS PROTEINS.
RX PubMed=15208321; DOI=10.1074/jbc.m401753200;
RA Van Dyck F., Delvaux E.L.D., Van de Ven W.J.M., Chavez M.V.;
RT "Repression of the transactivating capacity of the oncoprotein PLAG1 by
RT SUMOylation.";
RL J. Biol. Chem. 279:36121-36131(2004).
RN [15]
RP FUNCTION.
RX PubMed=14712223; DOI=10.1038/sj.onc.1207013;
RA Voz M.L., Mathys J., Hensen K., Pendeville H., Van Valckenborgh I.,
RA Van Huffel C., Chavez M., Van Damme B., De Moor B., Moreau Y.,
RA Van de Ven W.J.;
RT "Microarray screening for target genes of the proto-oncogene PLAG1.";
RL Oncogene 23:179-191(2004).
RN [16]
RP CHROMOSOMAL REARRANGEMENT WITH HAS2.
RX PubMed=15642402; DOI=10.1016/j.cancergencyto.2004.04.017;
RA Morerio C., Rapella A., Rosanda C., Tassano E., Gambini C., Romagnoli G.,
RA Panarello C.;
RT "PLAG1-HAS2 fusion in lipoblastoma with masked 8q intrachromosomal
RT rearrangement.";
RL Cancer Genet. Cytogenet. 156:183-184(2005).
RN [17]
RP SUMOYLATION, ACETYLATION, MUTAGENESIS OF LYS-244; LYS-263 AND LYS-353, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16207715; DOI=10.1074/jbc.m504334200;
RA Zheng G., Yang Y.-C.;
RT "Sumoylation and acetylation play opposite roles in the transactivation of
RT PLAG1 and PLAGL2.";
RL J. Biol. Chem. 280:40773-40781(2005).
RN [18]
RP CHROMOSOMAL REARRANGEMENT WITH CHCHD7 AND TCEA1.
RX PubMed=16736500; DOI=10.1002/gcc.20346;
RA Asp J., Persson F., Kost-Alimova M., Stenman G.;
RT "CHCHD7-PLAG1 and TCEA1-PLAG1 gene fusions resulting from cryptic,
RT intrachromosomal 8q rearrangements in pleomorphic salivary gland
RT adenomas.";
RL Genes Chromosomes Cancer 45:820-828(2006).
RN [19]
RP INVOLVEMENT IN SRS4.
RX PubMed=28796236; DOI=10.1038/gim.2017.105;
RA Abi Habib W., Brioude F., Edouard T., Bennett J.T., Lienhardt-Roussie A.,
RA Tixier F., Salem J., Yuen T., Azzi S., Le Bouc Y., Harbison M.D.,
RA Netchine I.;
RT "Genetic disruption of the oncogenic HMGA2-PLAG1-IGF2 pathway causes fetal
RT growth restriction.";
RL Genet. Med. 20:250-258(2018).
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. Overexpression is associated with up-regulation of
CC IGFII, is frequently observed in hepatoblastoma, common primary liver
CC tumor in childhood. Cooperates with CBFB-MYH11, a fusion gene important
CC for myeloid leukemia. {ECO:0000269|PubMed:11888928,
CC ECO:0000269|PubMed:14695992, ECO:0000269|PubMed:14712223}.
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. {ECO:0000269|PubMed:11882654,
CC ECO:0000269|PubMed:15208321}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10646861,
CC ECO:0000269|PubMed:11882654, ECO:0000269|PubMed:16207715}. Note=Strong
CC nucleolar localization when sumoylation is inhibited.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6DJT9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6DJT9-2; Sequence=VSP_045183;
CC -!- TISSUE SPECIFICITY: Expressed in fetal tissues such as lung, liver and
CC kidney. Not detected or weak detection in normal adult tissues, but
CC highly expressed in salivary gland with benign or malignant
CC pleiomorphic adenomas with or without 8q12 aberrations, with
CC preferential occurrence in benign tumors. {ECO:0000269|PubMed:10029085,
CC ECO:0000269|PubMed:14695992, ECO:0000269|PubMed:9020842,
CC ECO:0000269|PubMed:9722527}.
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.
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.
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. {ECO:0000269|PubMed:16207715}.
CC -!- DISEASE: Silver-Russell syndrome 4 (SRS4) [MIM:618907]: A form of
CC Silver-Russell syndrome, a clinically heterogeneous condition
CC characterized by severe intrauterine growth retardation, poor postnatal
CC growth, craniofacial features such as a triangular shaped face and a
CC broad forehead, body asymmetry, and a variety of minor malformations.
CC The phenotypic expression changes during childhood and adolescence,
CC with the facial features and asymmetry usually becoming more subtle
CC with age. SRS4 inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:28796236}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=A chromosomal aberration involving PLAG1 is found in
CC salivary gland pleiomorphic adenomas, the most common benign epithelial
CC tumors of the salivary gland. Translocation t(3;8)(p21;q12) with
CC constitutively expressed beta-catenin/CTNNB1. Fusion occurs in the 5'-
CC regulatory regions, leading to promoter swapping between the 2 genes
CC and activation of PLAG1 expression in adenomas. The chimeric transcript
CC is formed by fusion of CTNNB1 exon 1 to PLAG1 exon 3. Reciprocal fusion
CC transcript consisting of PLAG1 exon 1 and CTNNB1 exon 2-16 is also
CC revealed in some adenomas (PubMed:9020842, PubMed:10029085).
CC Translocation t(3;8)(p21;q12) with transcription elongation factor
CC SII/TCEA1. The fusion transcript is composed of 5'-non-coding sequences
CC as well as 63 nucleotides of the coding region of TCEA1 fused to the
CC acceptor splice site of PLAG1 exon 3. The fusion transcript encodes a
CC truncated TCEA1-PLAG1 protein of 90 AA as well as an apparently normal
CC PLAG1 protein. Reciprocal fusion transcript PLAG1-TCEA1 is also present
CC in one adenoma (PubMed:10029085, PubMed:16736500). Translocation
CC t(5;8)(p13;q12) with leukemia inhibitory factor receptor LIFR. This
CC fusion occured in the 5'-non-coding sequences of both genes, exchanging
CC regulatory control element while preserving the coding sequences
CC (PubMed:9525740). Translocation t(6;8)(p21.3-22;q13) with Coiled-coil-
CC helix-coiled-coil-helix domain-containing protein 7/CHCHD7. Fusion
CC occurs in the 5' regulatory regions, leading to promoter swapping and
CC up-regulation of PLAG1 expression (PubMed:16736500). Ectopic expression
CC of PLAG1 under the control of promoters of distinct translocation
CC partner genes is a general pathogenetic mechanism for pleiomorphic
CC adenomas with 8q aberrations. These fusion genes are likely to be found
CC in adenomas with normal karyotype as this subgroup of tumors also
CC exhibit PLAG1 activation (PubMed:9020842, PubMed:10029085,
CC PubMed:9525740, PubMed:16736500). {ECO:0000269|PubMed:10029085,
CC ECO:0000269|PubMed:16736500, ECO:0000269|PubMed:9020842,
CC ECO:0000269|PubMed:9525740}.
CC -!- DISEASE: Note=A chromosomal aberration involving PLAG1 may be a cause
CC of lipoblastomas, which are benign tumors resulting from transformation
CC of adipocytes, usually diagnosed in children. 8q12.1 to 8q24.1
CC intrachromosomal rearrangement with hyaluronic acid synthase 2/HAS2
CC results in promoter swapping and activation of PLAG1 expression. The
CC breakpoint of HAS2 gene is in PLAG1 intron 1, whereas its coding
CC sequence starts at exon 2 or exon 3. Translocation t(7;8)(p22;q13) with
CC collagen 1A2/COL1A2. Fusion transcript COL1A2-PLAG1 as well as HAS2-
CC PLAG1 encode a full-length PLAG1 protein. {ECO:0000269|PubMed:10987300,
CC ECO:0000269|PubMed:15642402}.
CC -!- MISCELLANEOUS: Residual nuclear import after mutation of the nuclear
CC localization signal is assigned to zinc finger domains of PLAG1.
CC -!- MISCELLANEOUS: When cultured cells transformed by PLAG1 overexpression
CC are injected in nude mouse, rapidly growing tumors (fibrosarcomaS) are
CC observed at the site of inoculation.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92368.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PLAG1ID74.html";
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DR EMBL; U65002; AAC50995.1; -; mRNA.
DR EMBL; AK296933; BAG59484.1; -; mRNA.
DR EMBL; AB209131; BAD92368.1; ALT_INIT; mRNA.
DR EMBL; AC107952; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC075047; AAH75047.1; -; mRNA.
DR EMBL; BC075048; AAH75048.1; -; mRNA.
DR CCDS; CCDS47860.1; -. [Q6DJT9-2]
DR CCDS; CCDS6165.1; -. [Q6DJT9-1]
DR RefSeq; NP_001108106.1; NM_001114634.1. [Q6DJT9-1]
DR RefSeq; NP_001108107.1; NM_001114635.1. [Q6DJT9-2]
DR RefSeq; NP_002646.2; NM_002655.2. [Q6DJT9-1]
DR RefSeq; XP_011515846.1; XM_011517544.2. [Q6DJT9-2]
DR RefSeq; XP_016869065.1; XM_017013576.1. [Q6DJT9-1]
DR RefSeq; XP_016869066.1; XM_017013577.1. [Q6DJT9-2]
DR AlphaFoldDB; Q6DJT9; -.
DR SMR; Q6DJT9; -.
DR BioGRID; 111340; 7.
DR IntAct; Q6DJT9; 5.
DR MINT; Q6DJT9; -.
DR STRING; 9606.ENSP00000325546; -.
DR iPTMnet; Q6DJT9; -.
DR PhosphoSitePlus; Q6DJT9; -.
DR BioMuta; PLAG1; -.
DR DMDM; 74757442; -.
DR EPD; Q6DJT9; -.
DR MassIVE; Q6DJT9; -.
DR MaxQB; Q6DJT9; -.
DR PaxDb; Q6DJT9; -.
DR PeptideAtlas; Q6DJT9; -.
DR PRIDE; Q6DJT9; -.
DR ProteomicsDB; 4523; -.
DR ProteomicsDB; 66229; -. [Q6DJT9-1]
DR Antibodypedia; 1454; 259 antibodies from 26 providers.
DR DNASU; 5324; -.
DR Ensembl; ENST00000316981.8; ENSP00000325546.3; ENSG00000181690.8. [Q6DJT9-1]
DR Ensembl; ENST00000423799.6; ENSP00000404067.2; ENSG00000181690.8. [Q6DJT9-2]
DR Ensembl; ENST00000429357.2; ENSP00000416537.2; ENSG00000181690.8. [Q6DJT9-1]
DR GeneID; 5324; -.
DR KEGG; hsa:5324; -.
DR MANE-Select; ENST00000316981.8; ENSP00000325546.3; NM_002655.3; NP_002646.2.
DR UCSC; uc003xsr.5; human. [Q6DJT9-1]
DR CTD; 5324; -.
DR DisGeNET; 5324; -.
DR GeneCards; PLAG1; -.
DR GeneReviews; PLAG1; -.
DR HGNC; HGNC:9045; PLAG1.
DR HPA; ENSG00000181690; Low tissue specificity.
DR MalaCards; PLAG1; -.
DR MIM; 181030; phenotype.
DR MIM; 603026; gene.
DR MIM; 618907; phenotype.
DR neXtProt; NX_Q6DJT9; -.
DR OpenTargets; ENSG00000181690; -.
DR Orphanet; 454821; Pleomorphic salivary gland adenoma.
DR Orphanet; 397590; Silver-Russell syndrome due to a point mutation.
DR PharmGKB; PA33378; -.
DR VEuPathDB; HostDB:ENSG00000181690; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000159246; -.
DR HOGENOM; CLU_002678_66_1_1; -.
DR InParanoid; Q6DJT9; -.
DR OMA; GTENRHD; -.
DR PhylomeDB; Q6DJT9; -.
DR TreeFam; TF332024; -.
DR PathwayCommons; Q6DJT9; -.
DR SignaLink; Q6DJT9; -.
DR SIGNOR; Q6DJT9; -.
DR BioGRID-ORCS; 5324; 9 hits in 1097 CRISPR screens.
DR ChiTaRS; PLAG1; human.
DR GeneWiki; PLAG1; -.
DR GenomeRNAi; 5324; -.
DR Pharos; Q6DJT9; Tbio.
DR PRO; PR:Q6DJT9; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q6DJT9; protein.
DR Bgee; ENSG00000181690; Expressed in secondary oocyte and 138 other tissues.
DR ExpressionAtlas; Q6DJT9; baseline and differential.
DR Genevisible; Q6DJT9; HS.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
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; IDA:NTNU_SB.
DR GO; GO:0022612; P:gland morphogenesis; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0060736; P:prostate gland growth; IEA:Ensembl.
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 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Chromosomal rearrangement;
KW DNA-binding; Dwarfism; Isopeptide bond; Metal-binding; Nucleus;
KW Proto-oncogene; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..500
FT /note="Zinc finger protein PLAG1"
FT /id="PRO_0000295107"
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..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..84
FT /note="Interaction with KPNA2"
FT /evidence="ECO:0000269|PubMed:11882654"
FT REGION 41..242
FT /note="Decreased nuclear import with localization in the
FT nucleus but also in the cytoplasm"
FT REGION 243..500
FT /note="Activates transcription; Inhibition of nuclear
FT import due to lack of NLS and KPNA2 interaction"
FT REGION 243..384
FT /note="Repression domain; contains 3 sumoylation motifs and
FT massively decrease transcription activity"
FT REGION 365..388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..500
FT /note="Massively activates transcription"
FT MOTIF 22..25
FT /note="Nuclear localization signal"
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 CROSSLNK 263
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT VAR_SEQ 1..82
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045183"
FT VARIANT 458
FT /note="P -> T (in dbSNP:rs35883156)"
FT /evidence="ECO:0000269|PubMed:9020842"
FT /id="VAR_033212"
FT MUTAGEN 23..24
FT /note="RK->AA: Inhibition of KPNA2 interaction when
FT mutation occurs in the NLS; decreased nuclear import with
FT localization in the nucleus but also in the cytoplasm;
FT Complete inhibition of nuclear import when associated with
FT a lack of zinc-finger domains."
FT /evidence="ECO:0000269|PubMed:11882654"
FT MUTAGEN 31..32
FT /note="RK->AA: No inhibition of KPNA2 interaction and no
FT change in nuclear import."
FT /evidence="ECO:0000269|PubMed:11882654"
FT MUTAGEN 92
FT /note="H->A: Prevents formation of functional zinc-finger
FT 3; induces drastic decrease of DNA affinity and complete
FT modification of DNA binding specificity."
FT /evidence="ECO:0000269|PubMed:10646861"
FT MUTAGEN 227
FT /note="H->A: Prevents formation of functional zinc-finger 7
FT and inhibits DNA binding; No proliferation and
FT transformation of cultured cells."
FT /evidence="ECO:0000269|PubMed:10646861,
FT ECO:0000269|PubMed:11888928"
FT MUTAGEN 244
FT /note="K->R: Abolishes single and double sumoylation;
FT nuclear localization conserved. Increases transcriptional
FT activity and inhibits repression domain activity; when
FT associated with R-263 and R-353."
FT /evidence="ECO:0000269|PubMed:15208321,
FT ECO:0000269|PubMed:16207715"
FT MUTAGEN 263
FT /note="K->R: Decreases sumoylation; Abolishes double
FT sumoylation only; Nuclear localization conserved. Increases
FT transcriptional activity and inhibits repression domain
FT activity; when associated with R-244 and R-353."
FT /evidence="ECO:0000269|PubMed:15208321,
FT ECO:0000269|PubMed:16207715"
FT MUTAGEN 339
FT /note="T->A: No effect on transcription activation
FT capacity."
FT /evidence="ECO:0000269|PubMed:9722527"
FT MUTAGEN 340
FT /note="S->A: No effect on transcription activation
FT capacity."
FT /evidence="ECO:0000269|PubMed:9722527"
FT MUTAGEN 353
FT /note="K->R: No effect on sumoylation. Increases
FT transcriptional activity and inhibits repression domain
FT activity; when associated with R-244 and R-263."
FT /evidence="ECO:0000269|PubMed:15208321,
FT ECO:0000269|PubMed:16207715"
FT CONFLICT 276
FT /note="E -> D (in Ref. 3; BAD92368)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 55909 MW; CF022A132A1BFD43 CRC64;
MATVIPGDLS EVRDTQKVPS GKRKRGETKP RKNFPCQLCD KAFNSVEKLK VHSYSHTGER
PYKCIQQDCT KAFVSKYKLQ RHMATHSPEK THKCNYCEKM FHRKDHLKNH LHTHDPNKET
FKCEECGKNY NTKLGFKRHL ALHAATSGDL TCKVCLQTFE STGVLLEHLK SHAGKSSGGV
KEKKHQCEHC DRRFYTRKDV RRHMVVHTGR KDFLCQYCAQ RFGRKDHLTR HMKKSHNQEL
LKVKTEPVDF LDPFTCNVSV PIKDELLPVM SLPSSELLSK PFTNTLQLNL YNTPFQSMQS
SGSAHQMITT LPLGMTCPID MDTVHPSHHL SFKYPFSSTS YAISIPEKEQ PLKGEIESYL
MELQGGVPSS SQDSQASSSS KLGLDPQIGS LDDGAGDLSL SKSSISISDP LNTPALDFSQ
LFNFIPLNGP PYNPLSVGSL GMSYSQEEAH SSVSQLPPQT QDLQDPANTI GLGSLHSLSA
AFTSSLSTST TLPRFHQAFQ
