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Thymus high mobility group box protein TOX

PDB rendering based on 2co9.
Available structures
Symbols TOX; KIAA0808
External IDs OMIM606863 MGI2181659 HomoloGene8822 GeneCards: TOX Gene
RNA expression pattern
PBB GE TOX 204529 s at tn.png
PBB GE TOX 204530 s at tn.png
More reference expression data
Species Human Mouse
Entrez 9760 252838
Ensembl ENSG00000198846 ENSMUSG00000041272
UniProt O94900 Q66JW3
RefSeq (mRNA) NM_014729 XM_974192
RefSeq (protein) NP_055544 XP_979286
Location (UCSC) Chr 8:
59.88 - 60.19 Mb
Chr 4:
6.61 - 6.92 Mb
PubMed search [1] [2]

Thymocyte selection-associated high mobility group box protein TOX is a protein that in humans is encoded by the TOX gene.[1][2][3]

Structure and function

The TOX gene encodes a protein that belongs to a large superfamily of chromatin associated proteins that share an approximately 75 amino acid DNA binding motif, the HMG (high mobility group)-box (named after that found in the canonical member of the family, high mobility group protein 1). Some high mobility group (HMG) box proteins (e.g., LEF1) contain a single HMG box motif and bind DNA in a sequence-specific manner, while other members of this family (e.g., HMGB1) have multiple HMG boxes and bind DNA in a sequence-independent but structure-dependent manner. While TOX has a single HMG-box motif,[3] it is predicted to bind DNA in a sequence-independent manner.[4]. TOX is also a member of a small subfamily of proteins (TOX2, TOX3, and TOX4) that share almost identical HMG-box sequences.[4] TOX3 has been identified as a breast cancer susceptibility locus.[5][6] TOX is highly expressed in the thymus, the site of development of T lymphocytes. Knockout mice that lack TOX have a severe defect in development of certain subsets of T lymphocytes.[7]


  1. ^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Apr 1999). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res 5 (5): 277-86. PMID 9872452.  
  2. ^ Wilkinson B, Chen JY, Han P, Rufner KM, Goularte OD, Kaye J (Mar 2002). "TOX: an HMG box protein implicated in the regulation of thymocyte selection". Nat Immunol 3 (3): 272-80. doi:10.1038/ni767. PMID 11850626.  
  3. ^ a b "Entrez Gene: thymocyte selection-associated high mobility group box gene TOX".  
  4. ^ a b O'Flaherty E, Kaye J (April 2003). "TOX defines a conserved subfamily of HMG-box proteins". BMC Genomics 4 (1): 13. doi:10.1186/1471-2164-4-13. PMID 12697058. PMC 155677.  
  5. ^ Easton DF, Pooley KA, Dunning AM, et al. (June 2007). "Genome-wide association study identifies novel breast cancer susceptibility loci". Nature 447 (7148): 1087–93. doi:10.1038/nature05887. PMID 17529967.  
  6. ^ Stacey SN, Manolescu A, Sulem P, et al. (July 2007). "Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer". Nat. Genet. 39 (7): 865–9. doi:10.1038/ng2064. PMID 17529974.  
  7. ^ Aliahmad P, Kaye J (January 2008). "Development of all CD4 T lineages requires nuclear factor TOX". J. Exp. Med. 205 (1): 245–56. doi:10.1084/jem.20071944. PMID 18195075.  

Further reading

  • Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.". DNA Res. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.  
  • Sebastiani P, Wang L, Nolan VG, et al. (2008). "Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations.". Am. J. Hematol. 83 (3): 189–95. doi:10.1002/ajh.21048. PMID 17918249.  
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334.  
  • Aliahmad P, O'Flaherty E, Han P, et al. (2004). "TOX provides a link between calcineurin activation and CD8 lineage commitment.". J. Exp. Med. 199 (8): 1089–99. doi:10.1084/jem.20040051. PMID 15078895.  
  • Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.  


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