SOX10

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SRY (sex determining region Y)-box 10
Identifiers
Symbols SOX10 ; DOM; PCWH; WS2E; WS4; WS4C
External IDs OMIM602229 MGI98358 HomoloGene5055 GeneCards: SOX10 Gene
RNA expression pattern
PBB GE SOX10 209842 at tn.png
PBB GE SOX10 209843 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 6663 20665
Ensembl ENSG00000100146 ENSMUSG00000033006
UniProt P56693 Q04888
RefSeq (mRNA) NM_006941 NM_011437
RefSeq (protein) NP_008872 NP_035567
Location (UCSC) Chr 22:
38.37 – 38.38 Mb
Chr 15:
79.15 – 79.16 Mb
PubMed search [1] [2]

Transcription factor SOX-10 is a protein that in humans is encoded by the SOX10 gene.[1][2][3][4]

Function[edit]

This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional activator after forming a protein complex with other proteins. This protein acts as a nucleocytoplasmic shuttle protein and is important for neural crest and peripheral nervous system development.[4]

In melanocytic cells there is evidence that SOX10 gene expression may be regulated by MITF.[5]

Clinical significance[edit]

Mutations in this gene are associated with Waardenburg-Shah, Waardenburg-Hirschsprung disease,[4] and with uveal melanoma .[6]

Interactions[edit]

The interaction between SOX10 and PAX3 is studied best in human patients with Waardenburg syndrome, an autosomal dominant disorder which is divided into four different types based upon mutations in additional genes. SOX10 and PAX3 interactions are thought to be regulators of other genes involved in the symptoms of Waardenburg syndrome, particularly MITF which influences the development of melanocytes as well as neural crest formation. MITF expression can be transactivated by both SOX10 and PAX3 to have an additive effect.[7][8] The two genes have binding sites near one another on the upstream enhancer of the c-RET gene.[9] SOX10 is also thought to target dopachrome tautomerase through a synergistic interaction with MITF which then results in other melanocyte alteration.[10]

SOX10 can influence the generation of myelin protein transcription through its interactions proteins such as OLIG1 and EGR2,[11][12] which is important for the functionality of neurons. Other cofactors have been identified, such as SP1, OCT6, NMI, FOXD3 and SOX2[13]

The interaction between SOX10 and NMI seems to be coexpressed in glial cells, gliomas, and the spinal cord and has been shown to modulate the transcriptional activity of SOX10.[14]

See also[edit]

References[edit]

  1. ^ Pingault V, Bondurand N, Kuhlbrodt K, Goerich DE, Préhu MO, Puliti A et al. (Feb 1998). "SOX10 mutations in patients with Waardenburg-Hirschsprung disease". Nature Genetics 18 (2): 171–3. doi:10.1038/ng0298-171. PMID 9462749. 
  2. ^ Bondurand N, Kuhlbrodt K, Pingault V, Enderich J, Sajus M, Tommerup N et al. (Sep 1999). "A molecular analysis of the yemenite deaf-blind hypopigmentation syndrome: SOX10 dysfunction causes different neurocristopathies". Human Molecular Genetics 8 (9): 1785–9. doi:10.1093/hmg/8.9.1785. PMID 10441344. 
  3. ^ Huber WE, Price ER, Widlund HR, Du J, Davis IJ, Wegner M et al. (Nov 2003). "A tissue-restricted cAMP transcriptional response: SOX10 modulates alpha-melanocyte-stimulating hormone-triggered expression of microphthalmia-associated transcription factor in melanocytes". The Journal of Biological Chemistry 278 (46): 45224–30. doi:10.1074/jbc.M309036200. PMID 12944398. 
  4. ^ a b c "Entrez Gene: SOX10 SRY (sex determining region Y)-box 10". 
  5. ^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO et al. (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971. 
  6. ^ Das D, Kaur I, Ali MJ, Biswas NK, Das S, Kumar S et al. (Jul 2014). "Exome sequencing reveals the likely involvement of SOX10 in uveal melanoma". Optometry and Vision Science 91 (7): e185–92. doi:10.1097/OPX.0000000000000309. PMID 24927141. 
  7. ^ Potterf SB, Furumura M, Dunn KJ, Arnheiter H, Pavan WJ (July 2000). "Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3". Hum. Genet. 107 (1): 1–6. PMID 10982026. 
  8. ^ Bondurand N, Pingault V, Goerich DE, Lemort N, Le Caignec C, Wegner M et al. (August 2000). "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome". Hum. Mol. Genet. 9 (13): 1907–17. PMID 10942418. 
  9. ^ Lang D, Epstein JA (April 2003). "Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer". Hum. Mol. Genet. 12 (8): 937–45. doi:10.1093/hmg/ddg107. PMID 12668617. 
  10. ^ Ludwig A, Rehberg S, Wegner, M (January 2004). "Melanocyte-specific expression of dopachrome tautomerase is dependent on synergistic gene activation by the Sox10 and Mitf transcription factors". FEBS Letters 556 (1-3): 236–44. PMID 14706856. 
  11. ^ Li H, Lu Y, Smith HK, Richardson W (December 2007). "Olig1 and Sox10 Interact Synergistically to Drive Myelin Basic Protein Transcription in Oligodendrocytes". The Journal Of Neuroscience 27 (52): 14375–82. PMID 14706856. 
  12. ^ LeBlanc S, Ward R, Svaren, J (May 2007). "Neuropathy-Associated Egr2 Mutants Disrupt Cooperative Activation of Myelin Protein Zero by Egr2 and Sox10". Mol. Cell. Biol. 27 (9): 3521–29. PMID 1899967. 
  13. ^ Bondurand N, Sham MH (October 2013). "The role of SOX10 during enteric nervous system development". Dev. Biol. 382 (1): 330–43. PMID 23644063. 
  14. ^ Schlierf B, Lang S, Kosian T, Werner T, Wegner M (November 2011). "The high-mobility group transcription factor Sox10 interacts with the N-myc-interacting protein Nmi". J. Mol. Biol. 353 (5): 1033–42. PMID 16214168. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.