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NKX2-2 (NK2 homeobox 2)

Written2008-01Stephen L Lessnick, Leah A Owen
Department of Oncological Sciences, University of Utah School of Medicine, Center for Children, Huntsman Cancer Institute,, Division of Pediatric Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, Utah, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesNKX2B
NK-2 (Drosophila) homolog B
NK2 transcription factor related, locus 2 (Drosophila)
Alias_symbol (synonym)NKX2.2
HGNC (Hugo) NKX2-2
LocusID (NCBI) 4821
Atlas_Id 44177
Location 20p11.22  [Link to chromosome band 20p11]
Location_base_pair Starts at 21491660 and ends at 21494664 bp from pter ( according to hg19-Feb_2009)  [Mapping NKX2-2.png]
Fusion genes
(updated 2016)
NKX2-2 (20p11.22) / TM4SF1 (3q25.1)

DNA/RNA

Description Start- 21,439,648 base pairs from p arm terminus; End- 21,442,699 base pairs from p arm terminus; Size- 3,051 bases; Orientation- minus strand

Protein

 
  Schematic of NKX2-2 functional domains. The positions of the transcriptional repressor domain (TN), the homeodomain (HD), the NK2-specific domain (SD), and the transcriptional activation domain (TAD) are shown.
Description 273 amino acids; 30133 Da. NKX2-2 is a member of the NK2 family of homeobox transcription factors. It has known roles in the development of the CNS as well as pancreatic beta cell differentiation. In the CNS NKX2-2 is known to be activated by SHH signaling which is important for its initial role in ventral patterning. NKX2-2 expression has additionally been shown to be critical for the differentiation of oligodendrocytes, and in fact necessary for this process to occur. In both instances, NKX2-2 mediated transcripitional repression is both necessary and sufficient for these processes to occur. Regulation of NKX2-2 expression in the pancreas is less well understood. NKX2-2 knock-out mice die soon after birth from diabetic complications as a result of a lack of fully differentiated pancreatic beta cells. While NKX2-2 mediated transcriptional repression has been demonstrated to be necessary and sufficient for its role in ß-cell differentiation, it remains unclear whether NKX2-2 mediated transcriptional activation is important for NKX2-2 function in adult ß-cells.
Expression V3 neural progenitors; oligodendrocyte precursor cells; precursor and adult pancreatic beta cells.
Localisation Nuclear
Function NKX2-2 is a transcription factor
Homology NKX2-2 shares homology with other members of the NK2 family of transcription factors most notably in the TN transcriptional repression, DNA binding homeodomain, and specific domain regions.

Implicated in

Note
Entity Ewing's sarcoma
Prognosis Roughly 50% survival at 5 years for Ewing's sarcoma.
Cytogenetics Ewing's sarcoma cells harbor the characteristic translocation t(11;22)(q24;q12) in roughly 90% of cases.
Hybrid/Mutated Gene t(11;22)(q24;q12) fuses the 5' region of the EWSR1 gene on chromosome 22 with the 3' portion of the FLI-1 gene on chromosome 11.
Abnormal Protein The translocation fusion product is termed EWS/FLI.
 
Schematic diagram of wild-type EWS, wild-type FLI, and the EWS/FLI fusion transcripts.
Oncogenesis NKX2-2 is up-regulated in Ewing's sarcoma by the EWS/FLI translocation protein product. NKX2.2 expression is necessary for the oncogenic phenotype of Ewing's sarcoma cells.
  

Bibliography

Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling.
Briscoe J, Sussel L, Serup P, Hartigan-O'Connor D, Jessell TM, Rubenstein JL, Ericson J
Nature. 1999 ; 398 (6728) : 622-627.
PMID 10217145
 
Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours.
Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, Kovar H, Joubert I, de Jong P, Rouleau G
Nature. 1992 ; 359 (6391) : 162-165.
PMID 1522903
 
Nkx2.2-repressor activity is sufficient to specify alpha-cells and a small number of beta-cells in the pancreatic islet.
Doyle MJ, Loomis ZL, Sussel L
Development (Cambridge, England). 2007 ; 134 (3) : 515-523.
PMID 17202186
 
Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation.
May WA, Gishizky ML, Lessnick SL, Lunsford LB, Lewis BC, Delattre O, Zucman J, Thomas G, Denny CT
Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 90 (12) : 5752-5756.
PMID 8516324
 
Groucho-mediated transcriptional repression establishes progenitor cell pattern and neuronal fate in the ventral neural tube.
Muhr J, Andersson E, Persson M, Jessell TM, Ericson J
Cell. 2001 ; 104 (6) : 861-873.
PMID 11290324
 
Identification of target genes in their native cellular context: an analysis of EWS/FLI in Ewing's sarcoma.
Owen LA, Lessnick SL
Cell cycle (Georgetown, Tex.). 2006 ; 5 (18) : 2049-2053.
PMID 16969112
 
Expression profiling of EWS/FLI identifies NKX2.2 as a critical target gene in Ewing's sarcoma.
Smith R, Owen LA, Trem DJ, Wong JS, Whangbo JS, Golub TR, Lessnick SL
Cancer cell. 2006 ; 9 (5) : 405-416.
PMID 16697960
 
Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cells.
Sussel L, Kalamaras J, Hartigan-O'Connor DJ, Meneses JJ, Pedersen RA, Rubenstein JL, German MS
Development (Cambridge, England). 1998 ; 125 (12) : 2213-2221.
PMID 9584121
 
Intramolecular control of transcriptional activity by the NK2-specific domain in NK-2 homeodomain proteins.
Watada H, Mirmira RG, Kalamaras J, German MS
Proceedings of the National Academy of Sciences of the United States of America. 2000 ; 97 (17) : 9443-9448.
PMID 10944215
 
Stage-specific expression of myelin basic protein in oligodendrocytes involves Nkx2.2-mediated repression that is relieved by the Sp1 transcription factor.
Wei Q, Miskimins WK, Miskimins R
The Journal of biological chemistry. 2005 ; 280 (16) : 16284-16294.
PMID 15695521
 

Citation

This paper should be referenced as such :
Lessnick, SL ; Owen, LA
NKX2-2 (NK2 homeobox 2)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(5):375-376.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/NKX22ID44177ch20p11.html


External links

Nomenclature
HGNC (Hugo)NKX2-2   7835
Cards
AtlasNKX22ID44177ch20p11
Entrez_Gene (NCBI)NKX2-2  4821  NK2 homeobox 2
AliasesNKX2.2; NKX2B
GeneCards (Weizmann)NKX2-2
Ensembl hg19 (Hinxton)ENSG00000125820 [Gene_View]  chr20:21491660-21494664 [Contig_View]  NKX2-2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000125820 [Gene_View]  chr20:21491660-21494664 [Contig_View]  NKX2-2 [Vega]
ICGC DataPortalENSG00000125820
TCGA cBioPortalNKX2-2
AceView (NCBI)NKX2-2
Genatlas (Paris)NKX2-2
WikiGenes4821
SOURCE (Princeton)NKX2-2
Genetics Home Reference (NIH)NKX2-2
Genomic and cartography
GoldenPath hg19 (UCSC)NKX2-2  -     chr20:21491660-21494664 -  20p11.22   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)NKX2-2  -     20p11.22   [Description]    (hg38-Dec_2013)
EnsemblNKX2-2 - 20p11.22 [CytoView hg19]  NKX2-2 - 20p11.22 [CytoView hg38]
Mapping of homologs : NCBINKX2-2 [Mapview hg19]  NKX2-2 [Mapview hg38]
OMIM604612   
Gene and transcription
Genbank (Entrez)BC075092 BC075093 BM314196 BQ632044 BU070383
RefSeq transcript (Entrez)NM_002509
RefSeq genomic (Entrez)NC_000020 NC_018931 NG_042186 NT_011387 NW_004929416
Consensus coding sequences : CCDS (NCBI)NKX2-2
Cluster EST : UnigeneHs.516922 [ NCBI ]
CGAP (NCI)Hs.516922
Alternative Splicing GalleryENSG00000125820
Gene ExpressionNKX2-2 [ NCBI-GEO ]   NKX2-2 [ EBI - ARRAY_EXPRESS ]   NKX2-2 [ SEEK ]   NKX2-2 [ MEM ]
Gene Expression Viewer (FireBrowse)NKX2-2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4821
GTEX Portal (Tissue expression)NKX2-2
Protein : pattern, domain, 3D structure
UniProt/SwissProtO95096   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO95096  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO95096
Splice isoforms : SwissVarO95096
PhosPhoSitePlusO95096
Domaine pattern : Prosite (Expaxy)HOMEOBOX_1 (PS00027)    HOMEOBOX_2 (PS50071)   
Domains : Interpro (EBI)Homeobox_CS    Homeobox_dom    Homeobox_metazoa    Homeodomain-like   
Domain families : Pfam (Sanger)Homeobox (PF00046)   
Domain families : Pfam (NCBI)pfam00046   
Domain families : Smart (EMBL)HOX (SM00389)  
Conserved Domain (NCBI)NKX2-2
DMDM Disease mutations4821
Blocks (Seattle)NKX2-2
SuperfamilyO95096
Human Protein AtlasENSG00000125820
Peptide AtlasO95096
HPRD05213
IPIIPI00028339   
Protein Interaction databases
DIP (DOE-UCLA)O95096
IntAct (EBI)O95096
FunCoupENSG00000125820
BioGRIDNKX2-2
STRING (EMBL)NKX2-2
ZODIACNKX2-2
Ontologies - Pathways
QuickGOO95096
Ontology : AmiGOcore promoter proximal region DNA binding  type B pancreatic cell development  pancreatic A cell fate commitment  type B pancreatic cell fate commitment  pancreatic PP cell fate commitment  chromatin binding  transcription factor activity, sequence-specific DNA binding  transcription coactivator activity  nucleoplasm  transcription, DNA-templated  smoothened signaling pathway  brain development  transcription factor binding  response to glucose  oligodendrocyte development  spinal cord motor neuron differentiation  spinal cord oligodendrocyte cell fate specification  optic nerve development  endocrine pancreas development  response to progesterone  sequence-specific DNA binding  negative regulation of neuron differentiation  positive regulation of neuron differentiation  positive regulation of transcription from RNA polymerase II promoter  digestive tract development  neuron fate specification  astrocyte differentiation  positive regulation of oligodendrocyte differentiation  positive regulation of sequence-specific DNA binding transcription factor activity  ventral spinal cord interneuron fate determination  
Ontology : EGO-EBIcore promoter proximal region DNA binding  type B pancreatic cell development  pancreatic A cell fate commitment  type B pancreatic cell fate commitment  pancreatic PP cell fate commitment  chromatin binding  transcription factor activity, sequence-specific DNA binding  transcription coactivator activity  nucleoplasm  transcription, DNA-templated  smoothened signaling pathway  brain development  transcription factor binding  response to glucose  oligodendrocyte development  spinal cord motor neuron differentiation  spinal cord oligodendrocyte cell fate specification  optic nerve development  endocrine pancreas development  response to progesterone  sequence-specific DNA binding  negative regulation of neuron differentiation  positive regulation of neuron differentiation  positive regulation of transcription from RNA polymerase II promoter  digestive tract development  neuron fate specification  astrocyte differentiation  positive regulation of oligodendrocyte differentiation  positive regulation of sequence-specific DNA binding transcription factor activity  ventral spinal cord interneuron fate determination  
Pathways : KEGGMaturity onset diabetes of the young   
REACTOMEO95096 [protein]
REACTOME PathwaysR-HSA-210746 Regulation of gene expression in endocrine-committed (NEUROG3+) progenitor cells [pathway]
REACTOME PathwaysR-HSA-210745 Regulation of gene expression in beta cells [pathway]
NDEx NetworkNKX2-2
Atlas of Cancer Signalling NetworkNKX2-2
Wikipedia pathwaysNKX2-2
Orthology - Evolution
OrthoDB4821
GeneTree (enSembl)ENSG00000125820
Phylogenetic Trees/Animal Genes : TreeFamNKX2-2
HOVERGENO95096
HOGENOMO95096
Homologs : HomoloGeneNKX2-2
Homology/Alignments : Family Browser (UCSC)NKX2-2
Gene fusions - Rearrangements
Fusion Cancer (Beijing)NKX2-2 [20p11.22]  -  TM4SF1 [3q25.1]  [FUSC002464]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerNKX2-2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)NKX2-2
dbVarNKX2-2
ClinVarNKX2-2
1000_GenomesNKX2-2 
Exome Variant ServerNKX2-2
ExAC (Exome Aggregation Consortium)NKX2-2 (select the gene name)
Genetic variants : HAPMAP4821
Genomic Variants (DGV)NKX2-2 [DGVbeta]
DECIPHER (Syndromes)20:21491660-21494664  ENSG00000125820
CONAN: Copy Number AnalysisNKX2-2 
Mutations
ICGC Data PortalNKX2-2 
TCGA Data PortalNKX2-2 
Broad Tumor PortalNKX2-2
OASIS PortalNKX2-2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICNKX2-2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDNKX2-2
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 NKX2-2
DgiDB (Drug Gene Interaction Database)NKX2-2
DoCM (Curated mutations)NKX2-2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)NKX2-2 (select a term)
intoGenNKX2-2
NCG5 (London)NKX2-2
Cancer3DNKX2-2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604612   
Orphanet
MedgenNKX2-2
Genetic Testing Registry NKX2-2
NextProtO95096 [Medical]
TSGene4821
GENETestsNKX2-2
Huge Navigator NKX2-2 [HugePedia]
snp3D : Map Gene to Disease4821
BioCentury BCIQNKX2-2
ClinGenNKX2-2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4821
Chemical/Pharm GKB GenePA31642
Clinical trialNKX2-2
Miscellaneous
canSAR (ICR)NKX2-2 (select the gene name)
Probes
Litterature
PubMed25 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineNKX2-2
EVEXNKX2-2
GoPubMedNKX2-2
iHOPNKX2-2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Nov 18 20:03:56 CET 2016

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