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NKX2-2 (NK2 homeobox 2)

Identity

Other namesNKX2.2
NKX2B
HGNC (Hugo) NKX2-2
LocusID (NCBI) 4821
Location 20p11.22
Location_base_pair Starts at 21491660 and ends at 21494664 bp from pter ( according to hg19-Feb_2009)  [Mapping]

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

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.
  

External links

Nomenclature
HGNC (Hugo)NKX2-2   7835
Cards
AtlasNKX22ID44177ch20p11
Entrez_Gene (NCBI)NKX2-2  4821  NK2 homeobox 2
GeneCards (Weizmann)NKX2-2
Ensembl (Hinxton)ENSG00000125820 [Gene_View]  chr20:21491660-21494664 [Contig_View]  NKX2-2 [Vega]
ICGC DataPortalENSG00000125820
cBioPortalNKX2-2
AceView (NCBI)NKX2-2
Genatlas (Paris)NKX2-2
WikiGenes4821
SOURCE (Princeton)NM_002509
Genomic and cartography
GoldenPath (UCSC)NKX2-2  -  20p11.22   chr20:21491660-21494664 -  20p11.22   [Description]    (hg19-Feb_2009)
EnsemblNKX2-2 - 20p11.22 [CytoView]
Mapping of homologs : NCBINKX2-2 [Mapview]
OMIM604612   
Gene and transcription
Genbank (Entrez)BC075092 BC075093 BM314196 BQ632044 BU070383
RefSeq transcript (Entrez)NM_002509
RefSeq genomic (Entrez)AC_000152 NC_000020 NC_018931 NT_011387 NW_001838652 NW_004929416
Consensus coding sequences : CCDS (NCBI)NKX2-2
Cluster EST : UnigeneHs.516922 [ NCBI ]
CGAP (NCI)Hs.516922
Alternative Splicing : Fast-db (Paris)GSHG0019052
Alternative Splicing GalleryENSG00000125820
Gene ExpressionNKX2-2 [ NCBI-GEO ]     NKX2-2 [ SEEK ]   NKX2-2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO95096 (Uniprot)
NextProtO95096  [Medical]
With graphics : InterProO95096
Splice isoforms : SwissVarO95096 (Swissvar)
Domaine pattern : Prosite (Expaxy)HOMEOBOX_1 (PS00027)    HOMEOBOX_2 (PS50071)   
Domains : Interpro (EBI)Homeobox_CS [organisation]   Homeobox_dom [organisation]   Homeobox_metazoa [organisation]   Homeodomain-like [organisation]  
Related proteins : CluSTrO95096
Domain families : Pfam (Sanger)Homeobox (PF00046)   
Domain families : Pfam (NCBI)pfam00046   
Domain families : Smart (EMBL)HOX (SM00389)  
DMDM Disease mutations4821
Blocks (Seattle)O95096
Human Protein AtlasENSG00000125820 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasO95096
HPRD05213
IPIIPI00028339   
Protein Interaction databases
DIP (DOE-UCLA)O95096
IntAct (EBI)O95096
FunCoupENSG00000125820
BioGRIDNKX2-2
InParanoidO95096
Interologous Interaction database O95096
IntegromeDBNKX2-2
STRING (EMBL)NKX2-2
Ontologies - Pathways
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  sequence-specific DNA binding transcription factor activity  transcription coactivator activity  nucleoplasm  transcription, DNA-templated  smoothened signaling pathway  brain development  transcription factor binding  oligodendrocyte development  spinal cord motor neuron differentiation  spinal cord oligodendrocyte cell fate specification  endocrine pancreas development  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  sequence-specific DNA binding transcription factor activity  transcription coactivator activity  nucleoplasm  transcription, DNA-templated  smoothened signaling pathway  brain development  transcription factor binding  oligodendrocyte development  spinal cord motor neuron differentiation  spinal cord oligodendrocyte cell fate specification  endocrine pancreas development  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   
Protein Interaction DatabaseNKX2-2
Wikipedia pathwaysNKX2-2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)NKX2-2
snp3D : Map Gene to Disease4821
SNP (GeneSNP Utah)NKX2-2
SNP : HGBaseNKX2-2
Genetic variants : HAPMAPNKX2-2
Exome VariantNKX2-2
1000_GenomesNKX2-2 
ICGC programENSG00000125820 
Somatic Mutations in Cancer : COSMICNKX2-2 
CONAN: Copy Number AnalysisNKX2-2 
Mutations and Diseases : HGMDNKX2-2
Genomic VariantsNKX2-2  NKX2-2 [DGVbeta]
dbVarNKX2-2
ClinVarNKX2-2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM604612   
MedgenNKX2-2
GENETestsNKX2-2
Disease Genetic AssociationNKX2-2
Huge Navigator NKX2-2 [HugePedia]  NKX2-2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneNKX2-2
Homology/Alignments : Family Browser (UCSC)NKX2-2
Phylogenetic Trees/Animal Genes : TreeFamNKX2-2
Chemical/Protein Interactions : CTD4821
Chemical/Pharm GKB GenePA31642
Clinical trialNKX2-2
Cancer Resource (Charite)ENSG00000125820
Other databases
Probes
Litterature
PubMed21 Pubmed reference(s) in Entrez
CoreMineNKX2-2
iHOPNKX2-2

Bibliography

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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written01-2008Stephen L Lessnick, Leah A Owen
Department of Oncological Sciences, University of Utah School of Medicine, Center for Children, Huntsman Cancer Institute, and Division of Pediatric Hematology/Oncology, University of Utah School of Medicine, Salt Lake City, Utah, USA

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 online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/NKX22ID44177ch20p11.html

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indexed on : Fri Jul 11 17:04:32 CEST 2014

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