PLAG1 (Pleomorphic adenoma gene 1)

Identity

HGNC	PLAG1
Location	8q12
Location_base_pair	Starts at 57236022 and ends at 57286413 bp from pter ( according to hg18-Mar_2006).
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	PLAG1   9045
Entrez_Gene	PLAG1  5324  pleiomorphic adenoma gene 1
	Cards
Atlas	PLAG1ID74
GeneCards	PLAG1
Ensembl	ENSG00000181690 [Gene_View]  PLAG1 [Vega]
Genatlas	PLAG1
	Genomic and cartography
GoldenPath	PLAG1  -  8q12   chr8:57236022-57286413 -  8q12   [Description]    (hg18-Mar_2006)
Ensembl	PLAG1 - 8q12 [CytoView]
NCBI	Mapview
OMIM	181030 Disease map [OMIM]
OMIM	603026 Disease map [OMIM]
HomoloGene	PLAG1
	Gene and transcription
Genbank	AB209131 [ ENTREZ ]
Genbank	AK296933 [ ENTREZ ]
Genbank	AK313663 [ ENTREZ ]
Genbank	BC075047 [ ENTREZ ]
Genbank	BC075048 [ ENTREZ ]
RefSeq	NM_001114634 [ SRS ]    NM_001114634 [ ENTREZ ]
RefSeq	NM_001114635 [ SRS ]    NM_001114635 [ ENTREZ ]
RefSeq	NM_002655 [ SRS ]    NM_002655 [ ENTREZ ]
RefSeq	AC_000051 [ SRS ]    AC_000051 [ ENTREZ ]
RefSeq	AC_000140 [ SRS ]    AC_000140 [ ENTREZ ]
RefSeq	NC_000008 [ SRS ]    NC_000008 [ ENTREZ ]
RefSeq	NT_008183 [ SRS ]    NT_008183 [ ENTREZ ]
RefSeq	NW_001839132 [ SRS ]    NW_001839132 [ ENTREZ ]
RefSeq	NW_923929 [ SRS ]    NW_923929 [ ENTREZ ]
CCDS	PLAG1 CCDS - NCBI
AceView	PLAG1 AceView - NCBI
Unigene	Hs.14968 [ SRS ]    Hs.14968 [ NCBI ]
Fast-db	5314 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	Q6DJT9 [ SRS]    Q6DJT9 [ EXPASY ]     Q6DJT9 [ INTERPRO ]     Q6DJT9 [ UNIPROT ] Q6DJT9 [ VarSplice FASTA ]
Prosite	PS00028 ZINC_FINGER_C2H2_1 [ SRS ]    PS00028 ZINC_FINGER_C2H2_1 [ Expasy ]
Prosite	PS50157 ZINC_FINGER_C2H2_2 [ SRS ]    PS50157 ZINC_FINGER_C2H2_2 [ Expasy ]
Interpro	IPR007087 Znf_C2H2 [ SRS ]    IPR007087 Znf_C2H2 [ EBI ]
Interpro	IPR015880 Znf_C2H2-like [ SRS ]    IPR015880 Znf_C2H2-like [ EBI ]
Interpro	IPR013087 Znf_C2H2/integrase_DNA-bd [ SRS ]    IPR013087 Znf_C2H2/integrase_DNA-bd [ EBI ]
CluSTr	Q6DJT9
Pfam	PF00096 zf-C2H2 [ SRS ]    PF00096 zf-C2H2 [ Sanger ]    pfam00096 [ NCBI-CDD ]
Smart	SM00355 ZnF_C2H2 [EMBL]
Prodom	PD000003 Znf_C2H2[INRA-Toulouse]
Prodom	Q6DJT9 PLAG1_HUMAN [ Domain structure ]   Q6DJT9 PLAG1_HUMAN  [ sequences sharing at least 1 domain ]
Blocks	Q6DJT9
HPRD	04321
	Protein Interaction databases
DIP	Q6DJT9
IntAct	Q6DJT9
	Polymorphism : SNP, mutations, diseases
OMIM	181030    [ map ]
OMIM	603026    [ map ]
GENETests	181030
GENETests	603026
SNP	PLAG1 [dbSNP-NCBI]
SNP	NM_001114634 [SNP-NCI]
SNP	NM_001114635 [SNP-NCI]
SNP	NM_002655 [SNP-NCI]
SNP	PLAG1 [GeneSNPs - Utah]  PLAG1] [HGBASE - SRS]
HAPMAP	PLAG1 [HAPMAP]
COSMIC	PLAG1 [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	PLAG1 [Translocation breakpoints In Cancer]
HGMD	PLAG1
Genetic Association	PLAG1
CDC HuGE	PLAG1
	General knowledge
Family Browser	PLAG1 [UCSC Family Browser]
SOURCE	NM_001114634
SOURCE	NM_001114635
SOURCE	NM_002655
SMD	Hs.14968
SAGE	Hs.14968
GO	transcription factor activity [Amigo]  transcription factor activity
GO	intracellular [Amigo]  intracellular
GO	nucleus [Amigo]  nucleus
GO	transcription [Amigo]  transcription
GO	regulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GO	zinc ion binding [Amigo]  zinc ion binding
GO	metal ion binding [Amigo]  metal ion binding
PubGene	PLAG1
TreeFam	PLAG1
CTD	5324 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	PLAG1 Related clones (RZPD - Berlin)
	PubMed
PubMed	25 Pubmed reference(s) in Entrez

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)

Written	06-2002	David 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

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Thu Nov 27 13:27:30 2008