Atlas of Genetics and Cytogenetics in Oncology and Haematology


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NKX2-2 (NK2 homeobox 2)

Identity

Other namesNKX2.2
NKX2B
HGNC NKX2-2
Location 20p11.22
Location_base_pair Starts at 21439652 and ends at 21442664 bp from pter (hg18-Mar_2006).

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
HGNCNKX2-2   7835
Entrez_GeneNKX2-2  4821  NK2 homeobox 2
Cards
AtlasNKX22ID44177ch20p11
GeneCardsNKX2-2
EnsemblNKX2-2 [Search_View]   ENSG00000125820 [Gene_View]
GenatlasNKX2-2
GeneLynxNKX2-2
eGenomeNKX2-2
euGene4821
Genomic and cartography
GoldenPathNKX2-2  -  20p11.22   chr20:21439652-21442664 -  20p11.22   [Description]    (hg18-Mar_2006)
EnsemblNKX2-2 - 20p11.22 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGeneNKX2-2
Gene and transcription
GenbankBC075092 [ ENTREZ ]
GenbankBC075093 [ ENTREZ ]
GenbankBM314196 [ ENTREZ ]
GenbankBQ632044 [ ENTREZ ]
GenbankCA772329 [ ENTREZ ]
RefSeqNM_002509 [ SRS ]    NM_002509 [ ENTREZ ]
RefSeqAC_000063 [ SRS ]    AC_000063 [ ENTREZ ]
RefSeqAC_000152 [ SRS ]    AC_000152 [ ENTREZ ]
RefSeqNC_000020 [ SRS ]    NC_000020 [ ENTREZ ]
RefSeqNT_011387 [ SRS ]    NT_011387 [ ENTREZ ]
RefSeqNW_001838652 [ SRS ]    NW_001838652 [ ENTREZ ]
RefSeqNW_927317 [ SRS ]    NW_927317 [ ENTREZ ]
AceViewNKX2-2 AceView - NCBI
UnigeneHs.516922 [ SRS ]    Hs.516922 [ NCBI ]     HS516922 [ spliceNest ]
Fast-db6733 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtO95096 [ SRS]    O95096 [ EXPASY ]     O95096 [ INTERPRO ]     O95096 [ UNIPROT ]
PrositePS00027 HOMEOBOX_1 [ SRS ]    PS00027 HOMEOBOX_1 [ Expasy ]
PrositePS50071 HOMEOBOX_2 [ SRS ]    PS50071 HOMEOBOX_2 [ Expasy ]
InterproIPR001356 Homeobox [ SRS ]    IPR001356 Homeobox [ EBI ]
InterproIPR012287 Homeodomain-rel [ SRS ]    IPR012287 Homeodomain-rel [ EBI ]
CluSTrO95096
PfamPF00046 Homeobox [ SRS ]    PF00046 Homeobox [ Sanger ]    pfam00046 [ NCBI-CDD ]
SmartSM00389 HOX [EMBL]
ProdomPD000010 Homeobox[INRA-Toulouse]
ProdomO95096 NKX22_HUMAN [ Domain structure ]   O95096 NKX22_HUMAN  [ sequences sharing at least 1 domain ]
BlocksO95096
HPRD05213
Protein Interaction databases
DIPO95096
IntActO95096
Polymorphism : SNP, mutations, diseases
OMIM604612    [ map ]   
GENECLINICS604612
SNPNKX2-2 [dbSNP-NCBI]  
SNPNM_002509 [SNP-NCI]  
SNPNKX2-2 [GeneSNPs - Utah]  NKX2-2] [HGBASE - SRS]
HAPMAPNKX2-2 [HAPMAP]  
HGMDNKX2-2
General knowledge
Family BrowserNKX2-2 [UCSC Family Browser]
SOURCENM_002509
SMDHs.516922
SAGEHs.516922
GOtranscription factor activity [Amigo]  transcription factor activity
GOprotein binding [Amigo]  protein binding
GOnucleus [Amigo]  nucleus
GOregulation of transcription, DNA-dependent [Amigo]  regulation of transcription, DNA-dependent
GOmulticellular organismal development [Amigo]  multicellular organismal development
GOnervous system development [Amigo]  nervous system development
GObrain development [Amigo]  brain development
GOoligodendrocyte development [Amigo]  oligodendrocyte development
GOspinal cord oligodendrocyte cell differentiation [Amigo]  spinal cord oligodendrocyte cell differentiation
GOendocrine pancreas development [Amigo]  endocrine pancreas development
GOsequence-specific DNA binding [Amigo]  sequence-specific DNA binding
GOpositive regulation of cell differentiation [Amigo]  positive regulation of cell differentiation
GOpositive regulation of transcription from RNA polymerase II promoter [Amigo]  positive regulation of transcription from RNA polymerase II promoter
GOcell development [Amigo]  cell development
GOneuron fate specification [Amigo]  neuron fate specification
KEGGMaturity onset diabetes of the young
PubGeneNKX2-2
TreeFamNKX2-2
CTD4821 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbeNKX2-2 Related clones (RZPD - Berlin)
PubMed
PubMed12 Pubmed reference(s) in Entrez

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. January 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/NKX22ID44177ch20p11.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Oct 11 12:54:29 2008


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