InnateDB Protein
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IDBP-370951.4
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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PLAG1
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Protein Name
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pleiomorphic adenoma gene 1
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Synonyms
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PSA; SGPA; ZNF912;
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000416537
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InnateDB Gene
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IDBG-22444 (PLAG1)
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Protein Structure
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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. {ECO:0000269PubMed:11888928, ECO:0000269PubMed:14695992, ECO:0000269PubMed:14712223}.
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Subcellular Localization |
Nucleus {ECO:0000269PubMed:10646861, ECO:0000269PubMed:11882654, ECO:0000269PubMed:16207715}. Note=Strong nucleolar localization when sumoylation is inhibited.
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Disease Associations |
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.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.
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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 aberrations, with preferential occurrence in benign tumors. {ECO:0000269PubMed:10029085, ECO:0000269PubMed:14695992, ECO:0000269PubMed:9020842, ECO:0000269PubMed:9722527}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 8 experimentally validated interaction(s) in this database.
Experimentally validated |
Total |
8
[view]
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Protein-Protein |
8
[view]
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Protein-DNA |
0
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Molecular Function |
Accession |
GO Term |
GO:0000978
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RNA polymerase II core promoter proximal region sequence-specific DNA binding
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GO:0000981
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sequence-specific DNA binding RNA polymerase II transcription factor activity
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GO:0001077
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RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
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GO:0003700
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sequence-specific DNA binding transcription factor activity
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GO:0046872
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metal ion binding
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Biological Process |
GO:0006366
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transcription from RNA polymerase II promoter
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GO:0045944
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positive regulation of transcription from RNA polymerase II promoter
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Cellular Component |
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PDB ID |
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InterPro |
IPR007087
Zinc finger, C2H2
IPR015880
Zinc finger, C2H2-like
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PFAM |
PF00096
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PRINTS |
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PIRSF |
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SMART |
SM00355
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TIGRFAMs |
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Modification |
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SwissProt |
Q6DJT9
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PhosphoSite |
PhosphoSite-Q6DJT9
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TrEMBL |
A7IT80
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UniProt Splice Variant |
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Entrez Gene |
5324
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UniGene |
Hs.613902
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RefSeq |
NP_001108106
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HUGO |
HGNC:9045
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OMIM |
603026
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CCDS |
CCDS6165
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HPRD |
04321
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IMGT |
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EMBL |
AB209131
AC107952
AK296933
BC075047
BC075048
CH471068
DQ478931
DQ478932
U65002
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GenPept |
AAC50995
AAH75047
AAH75048
ABF48561
ABF48562
BAD92368
BAG59484
EAW86774
EAW86775
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