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POU3F2 (POU class 3 homeobox 2)

Written2014-04Takuya Yazawa
Department of Surgical Pathology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-city, Chiba 230-8670, Japan

Abstract POU3F2, also known as BRN2, Oct7, and N-Oct3, is a member of the neural cell-specific class III POU domain transcription factors (Ryan and Rosenfeld, 1997). POU3F2-knockout causes the loss of specific neuronal lineages in the endocrine hypothalamus and the subsequent loss of the posterior pituitary gland (Nakai et al., 1995; Schonemann et al., 1995; Alvarez-Bolado et al., 1995). And also, transgenes of POU3F2 and some other few factors converted non-neural cells to neural cells in vitro (Ambasudhan et al., 2011; Lujan et al., 2012; Pang et al., 2011). These results indicate that POU3F2 is an indispensable transcription factor for neural differentiation and generation of normal nervous system, especially hypothalamus. There have been a few reports regarding the functions of POU3F2 in association with tumorigenesis. POU3F2 has been demonstrated to be an oncogene in malignant melanomas derived from the neuroectodermal cell lineage and to accelerate the growth of melanoma cells (Cook and Sturm, 2008). POU3F2 are also highly expressed in small cell lung cancers and closely associated with the cancer specific neural/neuroendocrine phenotype (Schreiber et al., 1992; Ishii et al., 2013; Sakaeda et al., 2013).

Keywords Transcription factor, POU domain, nervous system, neural development, hypothalamus, melanoma, small cell lung cancer, neuroendocrine

(Note : for Links provided by Atlas : click)

Identity

Alias_namesOTF7
POU domain class 3
Alias_symbol (synonym)POUF3
BRN2
OCT7
Other aliasN-Oct3
OTF-7
brn-2
oct-7
HGNC (Hugo) POU3F2
LocusID (NCBI) 5454
Atlas_Id 45747
Location 6q16.1  [Link to chromosome band 6q16]
Location_base_pair Starts at 98834704 and ends at 98838790 bp from pter ( according to hg19-Feb_2009)  [Mapping POU3F2.png]
Fusion genes
(updated 2016)
MAML3 (4q31.1) / POU3F2 (6q16.1)

DNA/RNA

 
  Schematic representation of POU3F2 gene and mRNA. The POU3F2 gene is located on the plus strand of 6q16.1 chromosome. It consists of one exon (4086 bp).
Description POU3F2 is intron-less gene. Coding region is located in 5' side of the gene.
Transcription 4108 base mRNA, coding sequence is 1332 base. There are no reports about transcriptional variant.

Protein

 
  Schematic illustrating POU3F2 protein. POU3F2 has poly-glycine and glutamic acid repeat in N-terminal side and POU-specific domain and homeodomain in C-terminal side.
Description POU3F2 belongs to the Class-III POU transcription factor family. All class-III POUs mainly express in some part of nervous system and regulate the development (Dominguez et al., 2013; Phippard et al., 1999). Two DNA binding domain, POU-specific domain, and homeodomain are conserved in POU transcription factor family.
Expression POU3F2 expresses in developing nervous system and hypothalamus (Andersen and Rosenfeld, 2001). It also localizes in the developing mouse spinal cord (Tanaka et al., 2004).
Localisation POU3F2 mainly localizes in nuclei.
Function POU3F2 makes homodimer or heterodimer with other transcription factor and recognize specific DNA motif. POU3F2 activates the transcription of near gene. It is reported that target genes of POU3F2 are some neural genes (Blaud et al., 2004), phosphodiesterase 5A (Arozarena et al., 2011), cadherin 13 (Ellmann et al., 2012), NKX2.1 (Sakaeda et al., 2013).
Homology POU3F2 shows highly similarity with the other class-III POU proteins (POU3F1, POU3F3, POU3F4) especially in the DNA binding domain.

Mutations

Note There is no report about mutation of POU3F2.

Implicated in

Note
  
Entity Melanoma
Note POU3F2 is highly expressed in melanoma cells and is related to the tumorigenesis and the growth (Cook and Sturm, 2008). Suppression of POU3F2 reduced proliferation activity and tumorigenic potential of melanoma cells (Thomson et al., 1995). It is reported that high POU3F2 expression is due to the activation of MAPK signaling pathway associated with BRAF gene mutation (Goodall et al., 2004).
  
  
Entity Small cell lung cancer
Note Small cell lung cancer (SCLC) highly expresses POU3F2 compared with non-SCLC. POU3F2 induces several neuroendocrine specific transcription factors and marker molecules and is associated to the cell viability (Schreiber et al., 1992; Ishii et al., 2013; Sakaeda et al., 2013).
  

Bibliography

Model of forebrain regionalization based on spatiotemporal patterns of POU-III homeobox gene expression, birthdates, and morphological features.
Alvarez-Bolado G, Rosenfeld MG, Swanson LW.
J Comp Neurol. 1995 May 1;355(2):237-95.
PMID 7608343
 
Direct reprogramming of adult human fibroblasts to functional neurons under defined conditions.
Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA, Ding S.
Cell Stem Cell. 2011 Aug 5;9(2):113-8. doi: 10.1016/j.stem.2011.07.002. Epub 2011 Jul 28.
PMID 21802386
 
POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease.
Andersen B, Rosenfeld MG.
Endocr Rev. 2001 Feb;22(1):2-35. (REVIEW)
PMID 11159814
 
Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A.
Arozarena I, Sanchez-Laorden B, Packer L, Hidalgo-Carcedo C, Hayward R, Viros A, Sahai E, Marais R.
Cancer Cell. 2011 Jan 18;19(1):45-57. doi: 10.1016/j.ccr.2010.10.029. Epub 2011 Jan 6.
PMID 21215707
 
Characteristic patterns of N Oct-3 binding to a set of neuronal promoters.
Blaud M, Vossen C, Joseph G, Alazard R, Erard M, Nieto L.
J Mol Biol. 2004 Jun 18;339(5):1049-58.
PMID 15178247
 
POU domain transcription factors: BRN2 as a regulator of melanocytic growth and tumourigenesis.
Cook AL, Sturm RA.
Pigment Cell Melanoma Res. 2008 Dec;21(6):611-26. doi: 10.1111/j.1755-148X.2008.00510.x. Epub 2008 Oct 22. (REVIEW)
PMID 18983536
 
POU-III transcription factors (Brn1, Brn2, and Oct6) influence neurogenesis, molecular identity, and migratory destination of upper-layer cells of the cerebral cortex.
Dominguez MH, Ayoub AE, Rakic P.
Cereb Cortex. 2013 Nov;23(11):2632-43. doi: 10.1093/cercor/bhs252. Epub 2012 Aug 14.
PMID 22892427
 
BRN2 is a transcriptional repressor of CDH13 (T-cadherin) in melanoma cells.
Ellmann L, Joshi MB, Resink TJ, Bosserhoff AK, Kuphal S.
Lab Invest. 2012 Dec;92(12):1788-800. doi: 10.1038/labinvest.2012.140. Epub 2012 Oct 15.
PMID 23069940
 
The Brn-2 transcription factor links activated BRAF to melanoma proliferation.
Goodall J, Wellbrock C, Dexter TJ, Roberts K, Marais R, Goding CR.
Mol Cell Biol. 2004 Apr;24(7):2923-31.
PMID 15024080
 
POU domain transcription factor BRN2 is crucial for expression of ASCL1, ND1 and neuroendocrine marker molecules and cell growth in small cell lung cancer.
Ishii J, Sato H, Sakaeda M, Shishido-Hara Y, Hiramatsu C, Kamma H, Shimoyamada H, Fujiwara M, Endo T, Aoki I, Yazawa T.
Pathol Int. 2013 Mar;63(3):158-68. doi: 10.1111/pin.12042.
PMID 23530560
 
Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells.
Lujan E, Chanda S, Ahlenius H, Sudhof TC, Wernig M.
Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2527-32. doi: 10.1073/pnas.1121003109. Epub 2012 Jan 30.
PMID 22308465
 
The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse.
Nakai S, Kawano H, Yudate T, Nishi M, Kuno J, Nagata A, Jishage K, Hamada H, Fujii H, Kawamura K, et al.
Genes Dev. 1995 Dec 15;9(24):3109-21.
PMID 8543155
 
Induction of human neuronal cells by defined transcription factors.
Pang ZP, Yang N, Vierbuchen T, Ostermeier A, Fuentes DR, Yang TQ, Citri A, Sebastiano V, Marro S, Sudhof TC, Wernig M.
Nature. 2011 May 26;476(7359):220-3. doi: 10.1038/nature10202.
PMID 21617644
 
Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear.
Phippard D, Lu L, Lee D, Saunders JC, Crenshaw EB 3rd.
J Neurosci. 1999 Jul 15;19(14):5980-9.
PMID 10407036
 
POU domain family values: flexibility, partnerships, and developmental codes.
Ryan AK, Rosenfeld MG.
Genes Dev. 1997 May 15;11(10):1207-25. (REVIEW)
PMID 9171367
 
Neural lineage-specific homeoprotein BRN2 is directly involved in TTF1 expression in small-cell lung cancer.
Sakaeda M, Sato H, Ishii J, Miyata C, Kamma H, Shishido-Hara Y, Shimoyamada H, Fujiwara M, Endo T, Tanaka R, Kondo H, Goya T, Aoki I, Yazawa T.
Lab Invest. 2013 Apr;93(4):408-21. doi: 10.1038/labinvest.2013.2. Epub 2013 Jan 28.
PMID 23358112
 
Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2.
Schonemann MD, Ryan AK, McEvilly RJ, O'Connell SM, Arias CA, Kalla KA, Li P, Sawchenko PE, Rosenfeld MG.
Genes Dev. 1995 Dec 15;9(24):3122-35.
PMID 8543156
 
Human small cell lung cancer expresses the octamer DNA-binding and nervous system-specific transcription factor N-Oct 3 (brain-2).
Schreiber E, Himmelmann A, Malipiero U, Tobler A, Stahel R, Fontana A.
Cancer Res. 1992 Nov 1;52(21):6121-4.
PMID 1327524
 
Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells.
Tanaka S, Kamachi Y, Tanouchi A, Hamada H, Jing N, Kondoh H.
Mol Cell Biol. 2004 Oct;24(20):8834-46.
PMID 15456859
 
The brn-2 gene regulates the melanocytic phenotype and tumorigenic potential of human melanoma cells.
Thomson JA, Murphy K, Baker E, Sutherland GR, Parsons PG, Sturm RA, Thomson F.
Oncogene. 1995 Aug 17;11(4):691-700.
PMID 7651733
 

Citation

This paper should be referenced as such :
T Yazawa
POU3F2 (POU class 3 homeobox 2)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(12):938-940.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/POU3F2ID45747ch6q16.html


External links

Nomenclature
HGNC (Hugo)POU3F2   9215
Cards
AtlasPOU3F2ID45747ch6q16
Entrez_Gene (NCBI)POU3F2  5454  POU class 3 homeobox 2
AliasesBRN2; N-Oct3; OCT7; OTF-7; 
OTF7; POUF3; brn-2; oct-7
GeneCards (Weizmann)POU3F2
Ensembl hg19 (Hinxton)ENSG00000184486 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000184486 [Gene_View]  chr6:98834704-98838790 [Contig_View]  POU3F2 [Vega]
ICGC DataPortalENSG00000184486
TCGA cBioPortalPOU3F2
AceView (NCBI)POU3F2
Genatlas (Paris)POU3F2
WikiGenes5454
SOURCE (Princeton)POU3F2
Genetics Home Reference (NIH)POU3F2
Genomic and cartography
GoldenPath hg38 (UCSC)POU3F2  -     chr6:98834704-98838790 +  6q16.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)POU3F2  -     6q16.1   [Description]    (hg19-Feb_2009)
EnsemblPOU3F2 - 6q16.1 [CytoView hg19]  POU3F2 - 6q16.1 [CytoView hg38]
Mapping of homologs : NCBIPOU3F2 [Mapview hg19]  POU3F2 [Mapview hg38]
OMIM600494   
Gene and transcription
Genbank (Entrez)AK095588 BC051699 BQ423615 BU183021 DA491157
RefSeq transcript (Entrez)NM_005604
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)POU3F2
Cluster EST : UnigeneHs.182505 [ NCBI ]
CGAP (NCI)Hs.182505
Alternative Splicing GalleryENSG00000184486
Gene ExpressionPOU3F2 [ NCBI-GEO ]   POU3F2 [ EBI - ARRAY_EXPRESS ]   POU3F2 [ SEEK ]   POU3F2 [ MEM ]
Gene Expression Viewer (FireBrowse)POU3F2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5454
GTEX Portal (Tissue expression)POU3F2
Protein : pattern, domain, 3D structure
UniProt/SwissProtP20265   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP20265  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP20265
Splice isoforms : SwissVarP20265
PhosPhoSitePlusP20265
Domaine pattern : Prosite (Expaxy)HOMEOBOX_1 (PS00027)    HOMEOBOX_2 (PS50071)    POU_1 (PS00035)    POU_2 (PS00465)    POU_3 (PS51179)   
Domains : Interpro (EBI)Homeobox-like    Homeobox_CS    Homeobox_dom    Lambda_DNA-bd_dom    POU    POU_dom    TF_POU_3   
Domain families : Pfam (Sanger)Homeobox (PF00046)    Pou (PF00157)   
Domain families : Pfam (NCBI)pfam00046    pfam00157   
Domain families : Smart (EMBL)HOX (SM00389)  POU (SM00352)  
Conserved Domain (NCBI)POU3F2
DMDM Disease mutations5454
Blocks (Seattle)POU3F2
SuperfamilyP20265
Human Protein AtlasENSG00000184486
Peptide AtlasP20265
HPRD02734
IPIIPI00300277   IPI00759484   IPI00759800   IPI00903176   
Protein Interaction databases
DIP (DOE-UCLA)P20265
IntAct (EBI)P20265
FunCoupENSG00000184486
BioGRIDPOU3F2
STRING (EMBL)POU3F2
ZODIACPOU3F2
Ontologies - Pathways
QuickGOP20265
Ontology : AmiGORNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  RNA polymerase II transcription coactivator activity  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  transcription factor complex  transcription from RNA polymerase II promoter  positive regulation of cell proliferation  epidermis development  negative regulation of gene expression  astrocyte development  cerebral cortex radially oriented cell migration  forebrain ventricular zone progenitor cell division  hypothalamus cell differentiation  neurohypophysis development  myelination in peripheral nervous system  neuron differentiation  positive regulation of multicellular organism growth  identical protein binding  positive regulation of transcription from RNA polymerase II promoter  regulation of axonogenesis  cellular response to organic substance  
Ontology : EGO-EBIRNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  RNA polymerase II transcription coactivator activity  transcription factor activity, sequence-specific DNA binding  protein binding  nucleus  transcription factor complex  transcription from RNA polymerase II promoter  positive regulation of cell proliferation  epidermis development  negative regulation of gene expression  astrocyte development  cerebral cortex radially oriented cell migration  forebrain ventricular zone progenitor cell division  hypothalamus cell differentiation  neurohypophysis development  myelination in peripheral nervous system  neuron differentiation  positive regulation of multicellular organism growth  identical protein binding  positive regulation of transcription from RNA polymerase II promoter  regulation of axonogenesis  cellular response to organic substance  
NDEx NetworkPOU3F2
Atlas of Cancer Signalling NetworkPOU3F2
Wikipedia pathwaysPOU3F2
Orthology - Evolution
OrthoDB5454
GeneTree (enSembl)ENSG00000184486
Phylogenetic Trees/Animal Genes : TreeFamPOU3F2
HOVERGENP20265
HOGENOMP20265
Homologs : HomoloGenePOU3F2
Homology/Alignments : Family Browser (UCSC)POU3F2
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPOU3F2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)POU3F2
dbVarPOU3F2
ClinVarPOU3F2
1000_GenomesPOU3F2 
Exome Variant ServerPOU3F2
ExAC (Exome Aggregation Consortium)POU3F2 (select the gene name)
Genetic variants : HAPMAP5454
Genomic Variants (DGV)POU3F2 [DGVbeta]
DECIPHERPOU3F2 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPOU3F2 
Mutations
ICGC Data PortalPOU3F2 
TCGA Data PortalPOU3F2 
Broad Tumor PortalPOU3F2
OASIS PortalPOU3F2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPOU3F2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPOU3F2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch POU3F2
DgiDB (Drug Gene Interaction Database)POU3F2
DoCM (Curated mutations)POU3F2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)POU3F2 (select a term)
intoGenPOU3F2
NCG5 (London)POU3F2
Cancer3DPOU3F2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600494   
Orphanet
MedgenPOU3F2
Genetic Testing Registry POU3F2
NextProtP20265 [Medical]
TSGene5454
GENETestsPOU3F2
Target ValidationPOU3F2
Huge Navigator POU3F2 [HugePedia]
snp3D : Map Gene to Disease5454
BioCentury BCIQPOU3F2
ClinGenPOU3F2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5454
Chemical/Pharm GKB GenePA33539
Clinical trialPOU3F2
Miscellaneous
canSAR (ICR)POU3F2 (select the gene name)
Probes
Litterature
PubMed42 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePOU3F2
EVEXPOU3F2
GoPubMedPOU3F2
iHOPPOU3F2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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