SOX2

SRY (sex determining region Y)-box 2
PDB rendering based on 1gt0.
Available structures PDB 1gt0, 1o4x
Identifiers
Symbols	SOX2; ANOP3; MCOPS3; MGC2413
External IDs	OMIM: 184429 MGI: 98364 HomoloGene: 68298 GeneCards: SOX2 Gene
Gene Ontology Molecular function • DNA binding • DNA binding • sequence-specific DNA binding transcription factor activity • sequence-specific DNA binding transcription factor activity • protein binding • miRNA binding • transcription regulatory region DNA binding Cellular component • nucleus • nucleus • nucleus • transcription factor complex • cytoplasm • cytosol Biological process • osteoblast differentiation • eye development • chromatin organization • transcription, DNA-dependent • transcription, DNA-dependent • regulation of transcription, DNA-dependent • regulation of transcription, DNA-dependent • cell cycle arrest • multicellular organismal development • response to wounding • regulation of gene expression • glial cell fate commitment • pituitary gland development • forebrain development • somatic stem cell maintenance • somatic stem cell maintenance • regulation of caspase activity • positive regulation of MAPKKK cascade • positive regulation of transcription, DNA-dependent • positive regulation of transcription from RNA polymerase II promoter • inner ear development • negative regulation of epithelial cell proliferation • response to growth factor stimulus • negative regulation of canonical Wnt receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6657	20674
Ensembl	ENSG00000181449	ENSMUSG00000074637
UniProt	P48431	P48432
RefSeq (mRNA)	NM_003106.3	NM_011443.3
RefSeq (protein)	NP_003097.1	NP_035573.3
Location (UCSC)	Chr 3: 181.43 – 181.43 Mb	Chr 3: 34.55 – 34.55 Mb
PubMed search	[1]	[2]

SRY (sex determining region Y)-box 2, also known as SOX2, is a transcription factor that is essential to maintain self-renewal of undifferentiated embryonic stem cells.

This intronless gene encodes a member of the SRY-related HMG-box (SOX) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate. The encoded protein may act as a transcriptional activator after forming a protein complex with other proteins. Mutations in this gene have been associated with bilateral anophthalmia, a severe form of structural eye malformation. This gene lies within an intron of another gene called SOX2 overlapping transcript (SOX2OT).

The ectopic expression of SOX2 may be related to abnormal differentiation of colorectal cancer cells.

Sox2 is one of the key transcription factors required in induced pluripotent stem cells. As forced Oct4 expression induces pluripotency in Sox2-null cells, a group of researchers concluded that the primary role of Sox2 in induced pluripotent stem cells is controlling Oct4 expression, and they perpetuate their own expression when expressed concurrently.

Interactions

SOX2 has been shown to interact with PAX6.

Further reading

• Kamachi Y, Uchikawa M, Kondoh H (2000). "Pairing SOX off: with partners in the regulation of embryonic development.". Trends Genet. 16 (4): 182–7. doi:10.1016/S0168-9525(99)01955-1. PMID 10729834. 
• Schepers GE, Teasdale RD, Koopman P (2002). "Twenty pairs of sox: extent, homology, and nomenclature of the mouse and human sox transcription factor gene families.". Dev. Cell 3 (2): 167–70. doi:10.1016/S1534-5807(02)00223-X. PMID 12194848. 
• Hever AM, Williamson KA, van Heyningen V (2007). "Developmental malformations of the eye: the role of PAX6, SOX2 and OTX2.". Clin. Genet. 69 (6): 459–70. doi:10.1111/j.1399-0004.2006.00619.x. PMID 16712695. 
• Yuan H, Corbi N, Basilico C, Dailey L (1995). "Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3.". Genes Dev. 9 (21): 2635–45. doi:10.1101/gad.9.21.2635. PMID 7590241. 
• Stevanovic M, Zuffardi O, Collignon J, et al. (1995). "The cDNA sequence and chromosomal location of the human SOX2 gene.". Mamm. Genome 5 (10): 640–2. doi:10.1007/BF00411460. PMID 7849401. 
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
• Helland R, Berglund GI, Otlewski J, et al. (1999). "High-resolution structures of three new trypsin-squash-inhibitor complexes: a detailed comparison with other trypsins and their complexes.". Acta Crystallogr. D Biol. Crystallogr. 55 (Pt 1): 139–48. doi:10.1107/S090744499801052X. PMID 10089404. 
• Güre AO, Stockert E, Scanlan MJ, et al. (2000). "Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer". Proc. Natl. Acad. Sci. U.S.A. 97 (8): 4198–203. doi:10.1073/pnas.97.8.4198. PMC 18195. PMID 10760287. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=18195. 
• Ambrosetti DC, Schöler HR, Dailey L, Basilico C (2000). "Modulation of the activity of multiple transcriptional activation domains by the DNA binding domains mediates the synergistic action of Sox2 and Oct-3 on the fibroblast growth factor-4 enhancer". J. Biol. Chem. 275 (30): 23387–97. doi:10.1074/jbc.M000932200. PMID 10801796. 
• Kamachi Y, Uchikawa M, Tanouchi A, et al. (2001). "Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development". Genes Dev. 15 (10): 1272–86. doi:10.1101/gad.887101. PMC 313803. PMID 11358870. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=313803. 
• 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. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Fantes J, Ragge NK, Lynch SA, et al. (2003). "Mutations in SOX2 cause anophthalmia". Nat. Genet. 33 (4): 461–3. doi:10.1038/ng1120. PMID 12612584. 
• Wiebe MS, Nowling TK, Rizzino A (2003). "Identification of novel domains within Sox-2 and Sox-11 involved in autoinhibition of DNA binding and partnership specificity". J. Biol. Chem. 278 (20): 17901–11. doi:10.1074/jbc.M212211200. PMID 12637543. 
• Aota S, Nakajima N, Sakamoto R, et al. (2003). "Pax6 autoregulation mediated by direct interaction of Pax6 protein with the head surface ectoderm-specific enhancer of the mouse Pax6 gene". Dev. Biol. 257 (1): 1–13. doi:10.1016/S0012-1606(03)00058-7. PMID 12710953. 
• Schepers G, Wilson M, Wilhelm D, Koopman P (2003). "SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro". J. Biol. Chem. 278 (30): 28101–8. doi:10.1074/jbc.M304067200. PMID 12732652. 
• Reményi A, Lins K, Nissen LJ, et al. (2003). "Crystal structure of a POU/HMG/DNA ternary complex suggests differential assembly of Oct4 and Sox2 on two enhancers". Genes Dev. 17 (16): 2048–59. doi:10.1101/gad.269303. PMC 196258. PMID 12923055. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=196258. 
• Williams DC, Cai M, Clore GM (2004). "Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex". J. Biol. Chem. 279 (2): 1449–57. doi:10.1074/jbc.M309790200. PMID 14559893. 
• Tsukamoto T, Inada K, Tanaka H, et al. (2004). "Down-regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2: inverse correlation during progression from gastric/intestinal-mixed to complete intestinal metaplasia". J. Cancer Res. Clin. Oncol. 130 (3): 135–45. doi:10.1007/s00432-003-0519-6. PMID 14655050. 

External links

• Young Lab- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells
• GeneReviews/NCBI/NIH/UW entry on SOX2-related eye disorders
• Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4 (Journal of Visualized Experiments)
• GeneReviews/NCBI/NIH/UW entry on Anophthalmia / Microphthalmia Overview