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PLAG1 (Pleomorphic adenoma gene 1)

Identity

HGNC (Hugo) PLAG1
Location 8q12
Location_base_pair Starts at 57236022 and ends at 57286413 bp from pter ( according to hg18-Mar_2006)  [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]  PLAG1 [Vega]
    AceView (NCBI)PLAG1
    Genatlas (Paris)PLAG1
    euGene (Indiana)5324
    SOURCE (Stanford)NM_001114634 NM_001114635 NM_002655
    Genomic and cartography
    GoldenPath (UCSC)PLAG1  -  8q12   chr8:57236022-57286413 -  8q12   [Description]    (hg18-Mar_2006)
    EnsemblPLAG1 - 8q12 [CytoView]
    Mapping of homologs : NCBIPLAG1 [Mapview]
    OMIM181030   603026   
    Gene and transcription
    Gene : Genbank (Entrez)AB209131 AK296933 AK313663 BC075047 BC075048
    Reference sequence (RefSeq transcript) :SRSNM_001114634 NM_001114635 NM_002655
    Reference transcript : EntrezNM_001114634 NM_001114635 NM_002655
    RefSeq genomic : SRSAC_000051 AC_000140 NC_000008 NT_008183 NW_001839132 NW_923929
    RefSeq genomic : EntrezAC_000051 AC_000140 NC_000008 NT_008183 NW_001839132 NW_923929
    Consensus coding sequences : CCDS NCBIPLAG1
    Cluster EST : UnigeneHs.14968 [ SRS ] Hs.14968 [ NCBI ]
    Alternative Splicing : Fast-db (Paris)5314
    Protein : pattern, domain, 3D structure
    Protein : UniProt/SwissProtQ6DJT9 (SRS) Q6DJT9 (Expasy) Q6DJT9 (Uniprot)
    With graphics : InterProQ6DJT9
    Splice isoforms : VarSplice FASTAQ6DJT9(VarSplice FASTA)
    Domaine pattern : Prosite (SRS)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
    Domain 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 SRSzf-C2H2 (PF00096)   
    Domain families : Pfam Sangerzf-C2H2 (PF00096)   
    Domain families : Pfam NCBIpfam00096   
    Domain families : Smart EMBLZnF_C2H2 (SM00355)
    Domain structure : Prodom (Prabi Lyon)Znf_C2H2 (PD000003)   
    Blocks (Seattle)Q6DJT9
    Crystal structure of protein : PDB SRS
    Crystal structure of protein : PDBSum
    Crystal structure of protein : IMB
    Crystal structure of protein : PDB RSDB
    HPRD04321
    Protein Interaction databases
    DIP (DOE-UCLA)Q6DJT9
    IntAct (EBI)Q6DJT9
    Polymorphism : SNP, mutations, diseases
    Single Nucleotide Polymorphism (SNP) : dbSNP NCBIPLAG1
    SNP : GeneSNP UtahPLAG1
    SNP : HGBasePLAG1
    Genetic variants : HAPMAPPLAG1
    Somatic Mutations in Cancer : COSMICPLAG1 
    Translocation Breakpoints in Cancer : TICdbPLAG1 
    Mutations and Diseases : HGMDPLAG1
    Hereditary diseases : OMIM181030    603026   
    Hereditary diseases : GENETests181030    603026   
    Diseases : Genetic AssociationPLAG1
    General knowledge
    Homologs : HomoloGenePLAG1
    Homology/Alignments : Family Browser UCSCPLAG1
    Phylogenetic Trees/Animal Genes : TreeFamPLAG1
    Chemical/Protein Interactions : CTD5324
    Keywords Ontology : AmiGOtranscription factor activity  intracellular  nucleus  transcription  regulation of transcription, DNA-dependent  zinc ion binding  metal ion binding  
    Keywords Ontology : EGO-EBItranscription factor activity  intracellular  nucleus  transcription  regulation of transcription, DNA-dependent  zinc ion binding  metal ion binding  
    Pathways : BIOCARTA
    Pathways : KEGG
    Other databases
    Probes
    Probes : ImagenesPLAG1 Related clones (RZPD - Berlin)
    Literature
    PubMed26 Pubmed reference(s) in Entrez
    PubGenePLAG1

    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

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    indexed on : Sat Jun 27 16:42:36 CEST 2009
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