Human Gene PLAG1 (ENST00000429357.2) from GENCODE V44
  Description: Transcription factor whose activation results in up- regulation of target genes, such as IGFII, leading to uncontrolled cell proliferation: when overexpressed in cultured cells, higher proliferation rate and transformation are observed. Other target genes such as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with PLAG1 induction. Proto-oncogene whose ectopic expression can trigger the development of pleomorphic adenomas of the salivary gland and lipoblastomas. Overexpression is associated with up-regulation of IGFII, is frequently observed in hepatoblastoma, common primary liver tumor in childhood. Cooperates with CBFB-MYH11, a fusion gene important for myeloid leukemia. (from UniProt Q6DJT9)
RefSeq Summary (NM_001114634): Pleomorphic adenoma gene 1 encodes a zinc finger protein with 2 putative nuclear localization signals. PLAG1, which is developmentally regulated, has been shown to be consistently rearranged in pleomorphic adenomas of the salivary glands. PLAG1 is activated by the reciprocal chromosomal translocations involving 8q12 in a subset of salivary gland pleomorphic adenomas. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008].
Gencode Transcript: ENST00000429357.2
Gencode Gene: ENSG00000181690.8
Transcript (Including UTRs)
   Position: hg38 chr8:56,166,243-56,211,300 Size: 45,058 Total Exon Count: 4 Strand: -
Coding Region
   Position: hg38 chr8:56,166,243-56,168,269 Size: 2,027 Coding Exon Count: 2 

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RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr8:56,166,243-56,211,300)mRNA (may differ from genome)Protein (500 aa)
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-  Comments and Description Text from UniProtKB
  ID: PLAG1_HUMAN
DESCRIPTION: RecName: Full=Zinc finger protein PLAG1; AltName: Full=Pleiomorphic adenoma gene 1 protein;
FUNCTION: Transcription factor whose activation results in up- regulation of target genes, such as IGFII, leading to uncontrolled cell proliferation: when overexpressed in cultured cells, higher proliferation rate and transformation are observed. Other target genes such as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with PLAG1 induction. Proto-oncogene whose ectopic expression can trigger the development of pleomorphic adenomas of the salivary gland and lipoblastomas. Overexpression is associated with up-regulation of IGFII, is frequently observed in hepatoblastoma, common primary liver tumor in childhood. Cooperates with CBFB-MYH11, a fusion gene important for myeloid leukemia.
SUBUNIT: Interacts with KPNA2, which escorts protein to the nucleus via interaction with nuclear localization signal. Interacts with E3 SUMO-protein ligase PIAS1, PIAS2 and PIAS4.
SUBCELLULAR LOCATION: Nucleus. Note=Strong nucleolar localization when sumoylation is inhibited.
TISSUE SPECIFICITY: Expressed in fetal tissues such as lung, liver and kidney. Not detected or weak detection in normal adult tissues, but highly expressed in salivary gland with benign or malignant pleiomorphic adenomas with or without 8q12 abberations, with preferential occurrence in benign tumors.
DOMAIN: C2H2-type zinc fingers 3 interacts with DNA-binding site G-clusterinc fingers. C2H2-type zinc fingers 6 and 7 interact with DNA-binding site core sequence.
PTM: Sumoylated with SUMO1; which inhibits transcriptional activity, but does not affect nuclear localization. Blockers of sumoylation pathway such as SENP3 and inactive UBE2I increases transcriptional capacity. Sumoylation is increased in the presence of PIAS1.
PTM: Acetylated by lysine acetyltransferase EP300; which activates transcriptional capacity. Lysine residues that are sumoylated also seem to be target for acetylation.
DISEASE: Note=A chromosomal aberration involving PLAG1 is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with constituvely expressed beta-catenin/CTNNB1. Fusion occurs in the 5'-regulatory regions, leading to promoter swapping between the 2 genes and activation of PLAG1 expression in adenomas. The chimeric transcript is formed by fusion of CTNNB1 exon 1 to PLAG1 exon 3. Reciprocal fusion transcript consisting of PLAG1 exon 1 and CTNNB1 exon 2-16 is also revealed in some adenomas. Translocation t(3;8)(p21;q12) with transcription elongation factor SII/TCEA1. The fusion transcript is composed of 5'-non-coding sequences as well as 63 nucleotides of the coding region of TCEA1 fused to the acceptor splice site of PLAG1 exon 3. The fusion transcript encodes a truncated TCEA1-PLAG1 protein of 90 AA as well as an apparently normal PLAG1 protein. Reciprocal fusion transcript PLAG1-TCEA1 is also present in one adenoma. Translocation t(5;8)(p13;q12) with leukemia inhibitory factor receptor LIFR. This fusion occured in the 5'-non-coding sequences of both genes, exchanging regulatory control element while preserving the coding sequences. Translocation t(6;8)(p21.3- 22;q13) with Coiled-coil-helix-coiled-coil-helix domain-containing protein 7/CHCHD7. Fusion occurs in the 5' regulatory regions, leading to promoter swapping and up-regulation of PLAG1 expression. Ectopic expression of PLAG1 under the control of promoters of distinct translocation partner genes is a general pathogenetic mechanism for pleiomorphic adenomas with 8q aberrations. These fusion genes are likely to be found in adenomas with normal karyotype as this subgroup of tumors also exhibit PLAG1 activation.
DISEASE: Note=A chromosomal aberration involving PLAG1 may be a cause of lipoblastomas, which are benign tumors resulting from transformation of adipocytes, usually diagnosed in children. 8q12.1 to 8q24.1 intrachromosomal rearrangement with hyaluronic acid synthase 2/HAS2 results in promoter swapping and activation of PLAG1 expression. The breakpoint of HAS2 gene is in PLAG1 intron 1, whereas its coding sequence starts at exon 2 or exon 3. Translocation t(7;8)(p22;q13) with collagen 1A2/COL1A2. Fusion transcript COL1A2-PLAG1 as well as HAS2-PLAG1 encode a full-length PLAG1 protein.
MISCELLANEOUS: Residual nuclear import after mutation of the nuclear localization signal is assigned to zinc finger domains of PLAG1.
MISCELLANEOUS: When cultured cells transformed by PLAG1 overexpression are injected in nude mouse, rapidly growing tumors (fibrosarcomaS) are observed at the site of inoculation.
SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein family.
SIMILARITY: Contains 7 C2H2-type zinc fingers.
SEQUENCE CAUTION: Sequence=BAD92368.1; Type=Erroneous initiation;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PLAG1ID74.html";

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: PLAG1
Diseases sorted by gene-association score: adenomas, salivary gland pleomorphic, somatic* (861), silver-russell syndrome* (165), adenoma (75), pleomorphic adenoma (51), hepatoblastoma (10), atypical lipomatous tumor (4), lipomatosis, multiple (4), lipoblastoma (3), vulvar leiomyoma (3), angiomatosis (3), vulvar benign neoplasm (3), gastrointestinal system benign neoplasm (2), organ system benign neoplasm (2), lipoadenoma (1), cell type benign neoplasm (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 4.01 RPKM in Nerve - Tibial
Total median expression: 54.77 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -124.00396-0.313 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007087 - Znf_C2H2
IPR015880 - Znf_C2H2-like
IPR013087 - Znf_C2H2/integrase_DNA-bd

Pfam Domains:
PF00096 - Zinc finger, C2H2 type

ModBase Predicted Comparative 3D Structure on Q6DJT9
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
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MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0046872 metal ion binding

Biological Process:
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0006915 apoptotic process
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0022612 gland morphogenesis
GO:0035264 multicellular organism growth
GO:0035265 organ growth
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0060252 positive regulation of glial cell proliferation
GO:0060736 prostate gland growth

Cellular Component:
GO:0005634 nucleus
GO:0016607 nuclear speck


-  Descriptions from all associated GenBank mRNAs
  U65002 - Human zinc finger protein PLAG1 mRNA, complete cds.
LF206382 - JP 2014500723-A/13885: Polycomb-Associated Non-Coding RNAs.
MA441959 - JP 2018138019-A/13885: Polycomb-Associated Non-Coding RNAs.
LF213715 - JP 2014500723-A/21218: Polycomb-Associated Non-Coding RNAs.
MA449292 - JP 2018138019-A/21218: Polycomb-Associated Non-Coding RNAs.
AB209131 - Homo sapiens mRNA for Pleiomorphic adenoma gene 1 variant protein.
AK296933 - Homo sapiens cDNA FLJ52324 complete cds, highly similar to Homo sapiens pleiomorphic adenoma gene 1 (PLAG1), mRNA.
BC075047 - Homo sapiens pleiomorphic adenoma gene 1, mRNA (cDNA clone MGC:103961 IMAGE:30915361), complete cds.
BC075048 - Homo sapiens pleiomorphic adenoma gene 1, mRNA (cDNA clone MGC:104123 IMAGE:30915577), complete cds.
EU446900 - Synthetic construct Homo sapiens clone IMAGE:100069827; IMAGE:100012109; FLH257042.01L pleiomorphic adenoma gene 1 (PLAG1) gene, encodes complete protein.
AK313663 - Homo sapiens cDNA, FLJ94244, highly similar to Homo sapiens pleiomorphic adenoma gene 1 (PLAG1), mRNA.
AB384858 - Synthetic construct DNA, clone: pF1KB3810, Homo sapiens PLAG1 gene for pleiomorphic adenoma gene 1, complete cds, without stop codon, in Flexi system.
AF221550 - Homo sapiens collagen 1 alpha 2/pleomorphic adenoma gene 1 (COL1A2/PLAG1 fusion) mRNA, partial sequence.
DQ478932 - Homo sapiens CHCHD7-PLAG1 fusion protein (CHCHD7/PLAG1) mRNA, partial cds.
DQ478931 - Homo sapiens CHCHD7-PLAG1 fusion protein (CHCHD7/PLAG1) mRNA, partial cds.
JD348206 - Sequence 329230 from Patent EP1572962.
JD109513 - Sequence 90537 from Patent EP1572962.
EF525169 - Homo sapiens FGFR1/PLAG1 fusion variant 2 (FGFR1/PLAG1 fusion) mRNA, partial sequence.
EF525168 - Homo sapiens FGFR1/PLAG1 fusion variant 1 (FGFR1/PLAG1 fusion) mRNA, partial sequence.
EF525170 - Homo sapiens FGFR1/PLAG1 fusion variant 3 (FGFR1/PLAG1 fusion) mRNA, complete cds.
JD263484 - Sequence 244508 from Patent EP1572962.
JD237959 - Sequence 218983 from Patent EP1572962.
AF221549 - Homo sapiens hyaluronan synthase 2/pleomorphic adenoma gene 1 (HAS2/PLAG1 fusion) mRNA, partial sequence.
JD094059 - Sequence 75083 from Patent EP1572962.
U78783 - Human tumor CG580, ectopic sequence fused to PLAG1 exon 3 mRNA.
JD367114 - Sequence 348138 from Patent EP1572962.
JD058746 - Sequence 39770 from Patent EP1572962.

-  Other Names for This Gene
  Alternate Gene Symbols: AK313663, ENST00000429357.1, PLAG1_HUMAN, Q59GH8, Q6DJT9, Q9Y4L2, uc010lyi.1, uc010lyi.2, uc010lyi.3, uc010lyi.4
UCSC ID: ENST00000429357.2
RefSeq Accession: NM_001114634
Protein: Q6DJT9 (aka PLAG1_HUMAN)
CCDS: CCDS6165.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene PLAG1:
rss (Silver-Russell Syndrome)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.