Atlas of Genetics and Cytogenetics in Oncology and Haematology

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PLAGL2 (Pleomorphic adenoma gene-like 2)

Written2008-01Abbas Abdollahi
Sbarro Institute for Cancer Research, Molecular Medicine, College of Science, Technology, BioLife Sciences Building, Suite 446, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA

(Note : for Links provided by Atlas : click)


Alias (NCBI)FLJ23283
HGNC Alias symbZNF900
HGNC Alias nameC2H2-type zinc finger protein
HGNC Previous namepleiomorphic adenoma gene-like 2
LocusID (NCBI) 5326
Atlas_Id 41738
Location 20q11.21  [Link to chromosome band 20q11]
Location_base_pair Starts at 32192504 and ends at 32207743 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PLAGL2.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


  PLAGL2 exons and corresponding nucleotide numbers on each GenBank sequence database are shown in this table.
Description PLAGL2 (PLAG-Like 2; a PLAG family member; GenBank accession number AF006005) was identified by homology searches of the database of expressed sequence tags (ESTs) and sequence similarity to zinc-finger region of the human PLAGL1/LOT1/ZAC1 and PLAG1 proteins.


Description PLAGL2 protein consists of 496 amino acid residues, six C2H2-type zinc finger domains in its amino-terminal region (shown as brown in the figure), and a proline- and serine-rich carboxyl terminus (shown as blue).
Expression Northern analysis showed that the PLAGL2 mRNA is expressed in fetal kidney, liver, lung, and brain but not in adult tissues. However, PCR analysis showed that PLAGL2 is ubiquitously expressed in almost all adult and fetal human tissues, except for the relatively low level of expression observed in fetal brain.
Localisation Nuclear.
Function PLAGL2 can bind and activate promoter; therefore, the oncogenic capacity of PLAGL2 may be mediated by activating the IGF-II mitogenic pathway. However, PLAGL2, possibly by association with HIF-1, may also have apoptotic role since it can activate Nip3 promoter and induce transcription in Balb/c3T3 fibroblasts and Neuro2a neuroblastoma cells, leading to apoptosis. PLAGL2 mRNA can be induced upon iron deficiency or hypoxia in mouse macrophage cell line RAW264.7, mouse erythroleukemia (MEL) cells, and Balb/c3T3 cells. In addition, PLAGL2 can also transactivate the surfactant protein-C (SP-C), a protein whose expression occurs principally in type II pneumocytes located in the distal lung alveolae. Additional data suggest that repression of the transactivating capacity of PLAGL2 may be directly related to sumoylation. Also, PLAGL2 protein is acetylated and activated by p300 and deacetylated and repressed by HDAC7, involving the lysine residues as the acetylation target. Therefore, it appears that the activity of PLAGL2 is tightly modulated by both sumoylation and acetylation, which may have opposite effects on their transactivation. Tip60 can modulate PLAGL2 function through both acetylation and inhibition of sumoylation, resulting in an enhanced PLAGL2-mediated transactivation. PLAGL2 can bind and stabilize (by preventing proteasomal degradation) Pirh2 dimer, a p53 inducible E3 ligase involved in the ubiquitination of p53. PLAGL2 can also regulate NCF2 gene expression through binding to the tumor necrosis factor (TNF)-alpha-responsive region of the NCF2 promoter, thus regulating p67(phox) expression and NADPH oxidase activity. PLAGL2 was recently found to aid in the efficient uptake of chylomicrons by intestinal lacteal vessels.
Homology Homologous to the human PLAG1 and PLAGL1 proteins.


Note Mutation has not been reported in the PLAGL2 coding region.

Implicated in

Entity Carcinogenicity
Note PLAGL2 is an oncoprotein involved in various malignancies including lipoblastomas, hepatoblastomas, and acute myeloid leukemia. PLAGL2 expression is increased in human cancers including acute myeloid leukemia (AML). The expression is increased in 20% of human AML samples. The PLAGL2 gene can independently cooperate with CBFB- MYH11 fusion gene in leukemogenesis. AML subtype M4 with eosinophilia is associated with a chromosome 16 inversion that creates a fusion gene CBFB-MYH11, encoding CBFbeta-SMMHC fusion protein. This fusion protein inhibits the core-binding factor (CBF), resulting in a block of hematopoietic differentiation and induction of leukemia in the presence of additional mutations.
Disease Cancer; lipoblastomas, hepatoblastomas, and acute myeloid leukemia.


LOT1 (ZAC1/PLAGL1) and its family members: mechanisms and functions.
Abdollahi A
Journal of cellular physiology. 2007 ; 210 (1) : 16-25.
PMID 17063461
Identification of a zinc-finger gene at 6q25: a chromosomal region implicated in development of many solid tumors.
Abdollahi A, Roberts D, Godwin AK, Schultz DC, Sonoda G, Testa JR, Hamilton TC
Oncogene. 1997 ; 14 (16) : 1973-1979.
PMID 9150364
Binding of pleomorphic adenoma gene-like 2 to the tumor necrosis factor (TNF)-alpha-responsive region of the NCF2 promoter regulates p67(phox) expression and NADPH oxidase activity.
Ammons MC, Siemsen DW, Nelson-Overton LK, Quinn MT, Gauss KA
The Journal of biological chemistry. 2007 ; 282 (24) : 17941-17952.
PMID 17462995
Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia.
Castilla LH, Perrat P, Martinez NJ, Landrette SF, Keys R, Oikemus S, Flanegan J, Heilman S, Garrett L, Dutra A, Anderson S, Pihan GA, Wolff L, Liu PP
Proceedings of the National Academy of Sciences of the United States of America. 2004 ; 101 (14) : 4924-4929.
PMID 15044690
Involvement of PLAGL2 in activation of iron deficient- and hypoxia-induced gene expression in mouse cell lines.
Furukawa T, Adachi Y, Fujisawa J, Kambe T, Yamaguchi-Iwai Y, Sasaki R, Kuwahara J, Ikehara S, Tokunaga R, Taketani S
Oncogene. 2001 ; 20 (34) : 4718-4727.
PMID 11498794
PLAGL2 translocation and SP-C promoter activity--a cellular response of lung cells to hypoxia.
Guo Y, Yang MC, Weissler JC, Yang YS
Biochemical and biophysical research communications. 2007 ; 360 (3) : 659-665.
PMID 17618602
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
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
Cbf beta-SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia.
Kuo YH, Landrette SF, Heilman SA, Perrat PN, Garrett L, Liu PP, Le Beau MM, Kogan SC, Castilla LH
Cancer cell. 2006 ; 9 (1) : 57-68.
PMID 16413472
Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11.
Landrette SF, Kuo YH, Hensen K, Barjesteh van Waalwijk van Doorn-Khosrovani S, Perrat PN, Van de Ven WJ, Delwel R, Castilla LH
Blood. 2005 ; 105 (7) : 2900-2907.
PMID 15585652
A zinc-finger protein, PLAGL2, induces the expression of a proapoptotic protein Nip3, leading to cellular apoptosis.
Mizutani A, Furukawa T, Adachi Y, Ikehara S, Taketani S
The Journal of biological chemistry. 2002 ; 277 (18) : 15851-15858.
PMID 11832486
Tip60 modulates PLAGL2-mediated transactivation by acetylation.
Ning J, Zheng G, Yang YC
Journal of cellular biochemistry. 2008 ; 103 (3) : 730-739.
PMID 17551969
Cloning and embryonic expression of zebrafish PLAG genes.
Pendeville H, Peers B, Kas K, Voz ML
Gene expression patterns : GEP. 2006 ; 6 (3) : 267-276.
PMID 16378757
Regulation of apoptosis and cell cycle arrest by Zac1, a novel zinc finger protein expressed in the pituitary gland and the brain.
Spengler D, Villalba M, Hoffmann A, Pantaloni C, Houssami S, Bockaert J, Journot L
The EMBO journal. 1997 ; 16 (10) : 2814-2825.
PMID 9184226
PLAG1, the prototype of the PLAG gene family: versatility in tumour development (review).
Van Dyck F, Declercq J, Braem CV, Van de Ven WJ
International journal of oncology. 2007 ; 30 (4) : 765-774.
PMID 17332914
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
Pleiomorphic adenoma gene-like-2, a zinc finger protein, transactivates the surfactant protein-C promoter.
Yang MC, Weissler JC, Terada LS, Deng F, Yang YS
American journal of respiratory cell and molecular biology. 2005 ; 32 (1) : 35-43.
PMID 15361364
PLAGL2 controls the stability of Pirh2, an E3 ubiquitin ligase for p53.
Zheng G, Ning J, Yang YC
Biochemical and biophysical research communications. 2007 ; 364 (2) : 344-350.
PMID 17950244
Sumoylation and acetylation play opposite roles in the transactivation of PLAG1 and PLAGL2.
Zheng G, Yang YC
The Journal of biological chemistry. 2005 ; 280 (49) : 40773-40781.
PMID 16207715


This paper should be referenced as such :
Abdollahi, A
PLAGL2 (pleomorphic adenoma gene-like 2)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(5):382-384.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)PLAGL2   9047
Entrez_Gene (NCBI)PLAGL2    PLAG1 like zinc finger 2
GeneCards (Weizmann)PLAGL2
Ensembl hg19 (Hinxton)ENSG00000126003 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000126003 [Gene_View]  ENSG00000126003 [Sequence]  chr20:32192504-32207743 [Contig_View]  PLAGL2 [Vega]
ICGC DataPortalENSG00000126003
Genatlas (Paris)PLAGL2
SOURCE (Princeton)PLAGL2
Genetics Home Reference (NIH)PLAGL2
Genomic and cartography
GoldenPath hg38 (UCSC)PLAGL2  -     chr20:32192504-32207743 -  20q11.21   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PLAGL2  -     20q11.21   [Description]    (hg19-Feb_2009)
GoldenPathPLAGL2 - 20q11.21 [CytoView hg19]  PLAGL2 - 20q11.21 [CytoView hg38]
Genome Data Viewer NCBIPLAGL2 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF006005 AK026951 AK292450 BC023655 D83784
RefSeq transcript (Entrez)NM_002657
Consensus coding sequences : CCDS (NCBI)PLAGL2
Gene ExpressionPLAGL2 [ NCBI-GEO ]   PLAGL2 [ EBI - ARRAY_EXPRESS ]   PLAGL2 [ SEEK ]   PLAGL2 [ MEM ]
Gene Expression Viewer (FireBrowse)PLAGL2 [ Firebrowse - Broad ]
GenevisibleExpression of PLAGL2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5326
GTEX Portal (Tissue expression)PLAGL2
Human Protein AtlasENSG00000126003-PLAGL2 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9UPG8   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9UPG8  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9UPG8
Domaine pattern : Prosite (Expaxy)ZINC_FINGER_C2H2_1 (PS00028)    ZINC_FINGER_C2H2_2 (PS50157)   
Domains : Interpro (EBI)PLAG1/PLAGL2    Znf_C2H2_sf    Znf_C2H2_type   
Domain families : Pfam (Sanger)zf-C2H2 (PF00096)   
Domain families : Pfam (NCBI)pfam00096   
Domain families : Smart (EMBL)ZnF_C2H2 (SM00355)  
Conserved Domain (NCBI)PLAGL2
AlphaFold pdb e-kbQ9UPG8   
Human Protein Atlas [tissue]ENSG00000126003-PLAGL2 [tissue]
Protein Interaction databases
IntAct (EBI)Q9UPG8
Ontologies - Pathways
Ontology : AmiGODNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  DNA-binding transcription factor activity  protein binding  nucleus  transcription, DNA-templated  regulation of transcription by RNA polymerase II  lipid metabolic process  post-embryonic development  chylomicron assembly  sequence-specific DNA binding  sequence-specific DNA binding  positive regulation of transcription by RNA polymerase II  metal ion binding  positive regulation of intrinsic apoptotic signaling pathway  
Ontology : EGO-EBIDNA-binding transcription factor activity, RNA polymerase II-specific  DNA-binding transcription activator activity, RNA polymerase II-specific  DNA-binding transcription factor activity  protein binding  nucleus  transcription, DNA-templated  regulation of transcription by RNA polymerase II  lipid metabolic process  post-embryonic development  chylomicron assembly  sequence-specific DNA binding  sequence-specific DNA binding  positive regulation of transcription by RNA polymerase II  metal ion binding  positive regulation of intrinsic apoptotic signaling pathway  
NDEx NetworkPLAGL2
Atlas of Cancer Signalling NetworkPLAGL2
Wikipedia pathwaysPLAGL2
Orthology - Evolution
GeneTree (enSembl)ENSG00000126003
Phylogenetic Trees/Animal Genes : TreeFamPLAGL2
Homologs : HomoloGenePLAGL2
Homology/Alignments : Family Browser (UCSC)PLAGL2
Gene fusions - Rearrangements
Fusion : QuiverPLAGL2
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPLAGL2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PLAGL2
Exome Variant ServerPLAGL2
GNOMAD BrowserENSG00000126003
Varsome BrowserPLAGL2
ACMGPLAGL2 variants
Genomic Variants (DGV)PLAGL2 [DGVbeta]
DECIPHERPLAGL2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPLAGL2 
ICGC Data PortalPLAGL2 
TCGA Data PortalPLAGL2 
Broad Tumor PortalPLAGL2
OASIS PortalPLAGL2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPLAGL2  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DPLAGL2
Mutations and Diseases : HGMDPLAGL2
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)PLAGL2
DoCM (Curated mutations)PLAGL2
CIViC (Clinical Interpretations of Variants in Cancer)PLAGL2
NCG (London)PLAGL2
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PLAGL2
NextProtQ9UPG8 [Medical]
Target ValidationPLAGL2
Huge Navigator PLAGL2 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDPLAGL2
Pharm GKB GenePA33380
Clinical trialPLAGL2
DataMed IndexPLAGL2
PubMed39 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Oct 8 21:25:19 CEST 2021

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