Atlas of Genetics and Cytogenetics in Oncology and Haematology

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PLAG1 (Pleomorphic adenoma gene 1)

Identity

HGNC (Hugo) PLAG1
LocusID (NCBI) 5324
Location 8q12.1
Location_base_pair Starts at 57073468 and ends at 57123859 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order (316 cR / 86 Mb from 8pter)

DNA/RNA

 
  Schematic view of the gene with approximate sizes of introns (kb) and exons (bp); the coding region (violet) translates into a 500 amino acid product with three functional subunits.
Description 7313 bp, 5 exons, 4 introns
Transcription At least two splicing variants, including and excluding the second exon

Protein

Description 500 amino acids with at least three functional regions : 1. Two N-terminal nuclear localisation signals, 2. Seven canonical zinc-finger domains, 3. A serine rich C-terminus
Expression Heart, placenta, spleen, prostate, testis, ovary, small intestine, several tumours
Localisation Nuclear
Function One of the N-terminal nuclear localisation signals (NLS1) interacts with karyopherin a2, which escorts proteins into the nucleus. Three of the seven Zn-finger domains are responsible for interaction with DNA and PLAG1 specifically activates transcription from its consensus binding site. Potential PLAG1 binding sites have been found in the promoter of IGF2.
Homology Mouse and rat Plag1

Mutations

Somatic Involved in chromosome rearrangements in epithelial and mesenchymal tumours. These are typically complex structural abnormalities, resulting in an exchange of regulatory elements and abnormal expression of PLAG1.

Implicated in

Entity Pleomorphic adenoma of the salivary gland
Disease Benign epithelial tumour
Prognosis Recovery after surgical removal
Cytogenetics The most common breakpoints are 3p21, 8q12, and 12q15
Hybrid/Mutated Gene The following translocations have been reported to result in hybrid genes involving PLAG1:
  • t(3;8)(p21;q12): CTNNB1 CTNNB1/PLAG1
  • t(5;8)(p13;q12): LIFR/PLAG1
  • Also, rearrangements between PLAG1 and TCEA1 have been detected in cases with normal karyotypes.
    • Abnormal Protein Fusions occur in the 5' regulatory regions, leading to promoter swapping and activation of PLAG1 expression while preserving coding sequences.
      
    Entity Carcinoma ex pleomorphic adenoma
    Disease Malignant epithelial tumour arising from pleomorphic adenoma
    Prognosis 30% five-year survival
    Cytogenetics Complex karyotype including t(3;8)(p23;q12)
    Hybrid/Mutated Gene Intragenic PLAG1 rearrangements demonstrated by fluorescence in situ hybridisation.
      
    Entity Lipoblastoma
    Disease Benign fat-forming tumour of childhood
    Prognosis Recovery after surgical removal
    Cytogenetics Structural abnormalities involving 8q11-13
    Hybrid/Mutated Gene The following rearrangements have been reported to result in hybrid genes involving PLAG1:
  • del(8)(q12q24), r(8): HAS2/PLAG1
  • t(7;8)(p22;q13): COL1A2/HAS2
    • Abnormal Protein Fusions occur in the 5' regulatory regions, leading promoter swapping and activation of PLAG1 expression while preserving coding sequences.
      

    Breakpoints

     

    External links

    Nomenclature
    HGNC (Hugo)PLAG1   9045
    Entrez_Gene (NCBI)PLAG1  5324  pleiomorphic adenoma gene 1
    Cards
    AtlasPLAG1ID74
    GeneCards (Weizmann)PLAG1
    Ensembl (Hinxton)ENSG00000181690 [Gene_View]  chr8:57073468-57123859 [Contig_View]  PLAG1 [Vega]
    AceView (NCBI)PLAG1
    Genatlas (Paris)PLAG1
    SOURCE (Stanford)NM_001114634 NM_001114635 NM_002655
    Genomic and cartography
    GoldenPath (UCSC)PLAG1  -  8q12.1   chr8:57073468-57123859 -  8q12   [Description]    (hg19-Feb_2009)
    EnsemblPLAG1 - 8q12 [CytoView]
    Mapping of homologs : NCBIPLAG1 [Mapview]
    OMIM181030   603026   
    Gene and transcription
    Genbank (Entrez)AB209131 AF221550 AK296933 AK313663 BC075047
    RefSeq transcript (SRS)NM_001114634 NM_001114635 NM_002655
    RefSeq transcript (Entrez)NM_001114634 NM_001114635 NM_002655
    RefSeq genomic (SRS)AC_000140 NC_000008 NC_018919 NG_023310 NT_008183 NW_001839132 NW_004078036
    RefSeq genomic (Entrez)AC_000140 NC_000008 NC_018919 NG_023310 NT_008183 NW_001839132 NW_004078036
    Consensus coding sequences : CCDS (NCBI)PLAG1
    Cluster EST : UnigeneHs.14968 [ SRS ] Hs.14968 [ NCBI ]
    CGAP (NCI)Hs.14968
    Alternative Splicing : Fast-db (Paris)GSHG0029589
    Alternative Splicing GalleryENSG00000181690
    Gene ExpressionPLAG1 [ NCBI-GEO ]   PLAG1 [ EBI - ARRAY_EXPRESS ]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ6DJT9 (SRS) Q6DJT9 (Uniprot)
    NextProtQ6DJT9
    With graphics : InterProQ6DJT9
    Splice isoforms : SwissVarQ6DJT9(Swissvar)
    Domaine pattern : Prosite (SRS)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
    Domaine pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
    Domains : Interpro (SRS)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
    Domains : Interpro (EBI)Znf_C2H2    Znf_C2H2-like    Znf_C2H2/integrase_DNA-bd   
    Related proteins : CluSTrQ6DJT9
    Domain families : Pfam (SRS)zf-C2H2 (PF00096)   
    Domain families : Pfam (Sanger)zf-C2H2 (PF00096)   
    Domain families : Pfam (NCBI)pfam00096   
    Domain families : Smart (EMBL)ZnF_C2H2 (SM00355)  
    DMDM5324
    Blocks (Seattle)Q6DJT9
    Human Protein AtlasENSG00000181690
    HPRD04321
    IPIIPI00787796   IPI00002594   
    Protein Interaction databases
    DIP (DOE-UCLA)Q6DJT9
    IntAct (EBI)Q6DJT9
    FunCoupENSG00000181690
    REACTOMEPLAG1
    Protein Interaction Database5324
    BioGRIDPLAG1
    InParanoidQ6DJT9
    Interologous Interaction database Q6DJT9
    IntegromeDBPLAG1
    Polymorphism : SNP, mutations, diseases
    SNP Single Nucleotide Polymorphism (NCBI)PLAG1
    SNP (GeneSNP Utah)PLAG1
    SNP : HGBasePLAG1
    Genetic variants : HAPMAPPLAG1
    Cancer Gene: CensusPLAG1 
    Somatic Mutations in Cancer : COSMICPLAG1 
    CONAN: Copy Number AnalysisPLAG1 
    Rearrangement : COSMICCHCHD7 [8q12.1]  -  PLAG1 [8q12.1]
    Rearrangement : COSMICCOL1A2 [7q21.3]  -  PLAG1 [8q12.1]
    Rearrangement : COSMICCTNNB1 [3p22.1]  -  PLAG1 [8q12.1]
    Rearrangement : COSMICFGFR1 [8p11.23]  -  PLAG1 [8q12.1]
    Rearrangement : COSMICHAS2 [8q24.13]  -  PLAG1 [8q12.1]
    Rearrangement : COSMICLIFR [5p13.1]  -  PLAG1 [8q12.1]
    Rearrangement : COSMICPLAG1 [8q12.1]  -  CTNNB1 [3p22.1]
    Rearrangement : COSMICTCEA1 [8q11.23]  -  PLAG1 [8q12.1]
    Translocation Breakpoints in Cancer : TICdbPLAG1 
    Mutations and Diseases : HGMDPLAG1
    OMIM181030    603026   
    GENETests181030    603026   
    Disease Genetic AssociationPLAG1
    Huge Navigator PLAG1 [HugePedia]  PLAG1 [HugeCancerGEM]
    Genomic VariantsPLAG1  PLAG1 [DGVbeta]
    snp3D : Map Gene to Disease5324
    General knowledge
    Homologs : HomoloGenePLAG1
    Homology/Alignments : Family Browser (UCSC)PLAG1
    Phylogenetic Trees/Animal Genes : TreeFamPLAG1
    Chemical/Protein Interactions : CTD5324
    Chemical/Pharm GKB GenePA33378
    Clinical trialPLAG1
    Cancer Resource (Charite)ENSG00000181690
    Ontology : AmiGODNA binding  sequence-specific DNA binding transcription factor activity  nucleus  transcription, DNA-dependent  zinc ion binding  positive regulation of gene expression  negative regulation of gene expression  gland morphogenesis  multicellular organism growth  organ growth  metal ion binding  positive regulation of glial cell proliferation  prostate gland growth  
    Ontology : EGO-EBIDNA binding  sequence-specific DNA binding transcription factor activity  nucleus  transcription, DNA-dependent  zinc ion binding  positive regulation of gene expression  negative regulation of gene expression  gland morphogenesis  multicellular organism growth  organ growth  metal ion binding  positive regulation of glial cell proliferation  prostate gland growth  
    Other databases
    Probes
    Litterature
    PubMed44 Pubmed reference(s) in Entrez
    PubGenePLAG1
    iHOPPLAG1

    Bibliography

    A 2-Mb YAC contig and physical map covering the chromosome 8q12 breakpoint cluster region in pleomorphic adenomas of the salivary glands.
    Kas K, Rˆijer E, Voz M, Meyen E, Stenman G, Van de Ven WJ
    Genomics. 1997 ; 43 (3) : 349-358.
    PMID 9268638
     
    Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations.
    Kas K, Voz ML, Rˆijer E, Astrˆm AK, Meyen E, Stenman G, Van de Ven WJ
    Nature genetics. 1997 ; 15 (2) : 170-174.
    PMID 9020842
     
    Transcriptional activation capacity of the novel PLAG family of zinc finger proteins.
    Kas K, Voz ML, Hensen K, Meyen E, Van de Ven WJ
    The Journal of biological chemistry. 1998 ; 273 (36) : 23026-23032.
    PMID 9722527
     
    The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter.
    Voz ML, Astrˆm AK, Kas K, Mark J, Stenman G, Van de Ven WJ
    Oncogene. 1998 ; 16 (11) : 1409-1416.
    PMID 9525740
     
    Conserved mechanism of PLAG1 activation in salivary gland tumors with and without chromosome 8q12 abnormalities: identification of SII as a new fusion partner gene.
    Astrˆm AK, Voz ML, Kas K, Rˆijer E, Wedell B, Mandahl N, Van de Ven W, Mark J, Stenman G
    Cancer research. 1999 ; 59 (4) : 918-923.
    PMID 10029085
     
    Pleomorphic adenoma gene 1 is expressed in cultured benign and malignant salivary gland tumor cells.
    Queimado L, Lopes C, Du F, Martins C, Bowcock AM, Soares J, Lovett M
    Laboratory investigation; a journal of technical methods and pathology. 1999 ; 79 (5) : 583-589.
    PMID 10334569
     
    Fluorescence in situ hybridization mapping of breakpoints in pleomorphic adenomas with 8q12-13 abnormalities identifies a subgroup of tumors without PLAG1 involvement.
    Rˆijer E, Kas K, Behrendt M, Van de Ven W, Stenman G
    Genes, chromosomes & cancer. 1999 ; 24 (1) : 78-82.
    PMID 9892112
     
    Evidence of involvement of the PLAG1 gene in lipoblastomas.
    Astrom A, D'Amore ES, Sainati L, Panarello C, Morerio C, Mark J, Stenman G
    International journal of oncology. 2000 ; 16 (6) : 1107-1110.
    PMID 10811981
     
    PLAG1 fusion oncogenes in lipoblastoma.
    Hibbard MK, Kozakewich HP, Dal Cin P, Sciot R, Tan X, Xiao S, Fletcher JA
    Cancer research. 2000 ; 60 (17) : 4869-4872.
    PMID 10987300
     
    PLAG1, the main translocation target in pleomorphic adenoma of the salivary glands, is a positive regulator of IGF-II.
    Voz ML, Agten NS, Van de Ven WJ, Kas K
    Cancer research. 2000 ; 60 (1) : 106-113.
    PMID 10646861
     
    First insights into the molecular basis of pleomorphic adenomas of the salivary glands.
    Voz ML, Van de Ven WJ, Kas K
    Advances in dental research. 2000 ; 14 : 81-83.
    PMID 11842929
     
    Histologic localization of PLAG1 (pleomorphic adenoma gene 1) in pleomorphic adenoma of the salivary gland: cytogenetic evidence of common origin of phenotypically diverse cells.
    Debiec-Rychter M, Van Valckenborgh I, Van den Broeck C, Hagemeijer A, Van de Ven WJ, Kas K, Van Damme B, Voz ML
    Laboratory investigation; a journal of technical methods and pathology. 2001 ; 81 (9) : 1289-1297.
    PMID 11555676
     
    PLAG1 alterations in lipoblastoma: involvement in varied mesenchymal cell types and evidence for alternative oncogenic mechanisms.
    Gisselsson D, Hibbard MK, Dal Cin P, Sciot R, Hsi BL, Kozakewich HP, Fletcher JA
    The American journal of pathology. 2001 ; 159 (3) : 955-962.
    PMID 11549588
     
    Characterization of chromosome aberrations in salivary gland tumors by FISH, including multicolor COBRA-FISH.
    Jin C, Martins C, Jin Y, Wiegant J, Wennerberg J, Dictor M, Gisselsson D, Strˆmbeck B, Fonseca I, Mitelman F, Tanke HJ, Hˆglund M, Mertens F
    Genes, chromosomes & cancer. 2001 ; 30 (2) : 161-167.
    PMID 11135432
     
    Assignment of the rat pleiomorphic adenoma genes (Plag1, Plagl1, Plagl2) by in situ hybridization and radiation hybrid mapping.
    Szpirer C, Kas K, Laes JF, RiviˆŪre M, Van Vooren P, Szpirer J
    Cytogenetics and cell genetics. 2001 ; 94 (1-2) : 94-95.
    PMID 11701966
     
    Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal.
    Braem CV, Kas K, Meyen E, Debiec-Rychter M, Van De Ven WJ, Voz ML
    The Journal of biological chemistry. 2002 ; 277 (22) : 19673-19678.
    PMID 11882654
     
    Expression of PLAG1 and HMGIC proteins and fusion transcripts in radiation-associated pleomorphic adenomas.
    Enlund F, Nordkvist A, Sahlin P, Mark J, Stenman G
    International journal of oncology. 2002 ; 20 (4) : 713-716.
    PMID 11894114
     
    The tumorigenic diversity of the three PLAG family members is associated with different DNA binding capacities.
    Hensen K, Van Valckenborgh IC, Kas K, Van de Ven WJ, Voz ML
    Cancer research. 2002 ; 62 (5) : 1510-1517.
    PMID 11888928
     
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    Contributor(s)

    Written06-2002David Gisselsson

    Citation

    This paper should be referenced as such :
    Gisselsson D . PLAG1 (Pleomorphic adenoma gene 1). Atlas Genet Cytogenet Oncol Haematol. June 2002 .
    URL : http://AtlasGeneticsOncology.org/Genes/PLAG1ID74.html

    This paper is referenced by INIST as such :
    http://documents.irevues.inist.fr/bitstream/2042/37897/1/06-2002-PLAG1ID74.pdf   [ Bibliographic record ]

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    indexed on : Wed May 1 13:12:04 CEST 2013
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