SOX10

SOX10
Identifiers
Aliases	SOX10, DOM, PCWH, WS2E, WS4, WS4C, SRY-box 10, SRY-box transcription factor 10, SOX-10
External IDs	OMIM: 602229; MGI: 98358; HomoloGene: 5055; GeneCards: SOX10; OMA:SOX10 - orthologs
Gene location (Human) Chr. Chromosome 22 (human) Band 22q13.1 Start 37,970,686 bp End 37,987,422 bp
Gene location (Mouse) Chr. Chromosome 15 (mouse) Band 15 E1|15 37.7 cM Start 79,039,108 bp End 79,049,440 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in inferior olivary nucleus sural nerve dorsal motor nucleus of vagus nerve inferior ganglion of vagus nerve trigeminal ganglion spinal ganglia C1 segment subthalamic nucleus ventral tegmental area parotid gland Top expressed in vestibular membrane of cochlear duct neural crest external carotid artery motor neuron parotid gland internal carotid artery optic nerve stria vascularis vestibular sensory epithelium lactiferous gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transcription coactivator activity transcription factor binding chromatin binding protein binding identical protein binding promoter-specific chromatin binding DNA binding DNA-binding transcription factor activity DNA-binding transcription factor activity, RNA polymerase II-specific RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Cellular component cytoplasm nucleoplasm nucleus chromatin mitochondrion mitochondrial outer membrane membrane extrinsic component of mitochondrial outer membrane Biological process regulation of transcription, DNA-templated regulation of transcription by RNA polymerase II anatomical structure morphogenesis transcription, DNA-templated stem cell differentiation negative regulation of transcription, DNA-templated transcription elongation from RNA polymerase II promoter negative regulation of Schwann cell proliferation positive regulation of gene expression positive regulation of myelination cellular response to progesterone stimulus positive regulation of transcription, DNA-templated oligodendrocyte development central nervous system myelination oligodendrocyte differentiation in utero embryonic development neural crest cell migration morphogenesis of an epithelium positive regulation of neuroblast proliferation central nervous system development peripheral nervous system development positive regulation of gliogenesis cell differentiation melanocyte differentiation lacrimal gland development negative regulation of apoptotic process positive regulation of transcription by RNA polymerase II cell maturation enteric nervous system development digestive tract morphogenesis developmental growth morphogenesis of a branching epithelium negative regulation of canonical Wnt signaling pathway Sources:Amigo / QuickGO
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: 37.97 – 37.99 Mb Chr 15: 79.04 – 79.05 Mb PubMed search
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Transcription factor SOX-10 is a protein that in humans is encoded by the SOX10 gene.

Function

This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and determination of cell fate. The encoded protein acts 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.

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

Mutations

Mutations in this gene are associated with Waardenburg–Shah syndrome and uveal melanoma.

Immunostain

SOX10 is used as an immunohistochemistry marker, being positive in:

• Neuroectodermal neoplasms of neural crest origin, especially:

• Melanoma, although desmoplastic melanomas may be only focally positive.
• Nevus

• 
  SOX10 immunohistochemistry in a dermal nevus, showing positively staining nevus cells (arrows)
• 
  SOX10 immunohistochemistry of normal skin (top) and atypical melanocytic proliferation (bottom), seen mainly in hair follicles.
• 
  SOX10 immunohistochemistry facilitates showing lentigo maligna, as an increased number of melanocytes along stratum basale and nuclear pleumorphism. The changes are continuous with the resection margin (inked in yellow, at left), conferring a diagnosis of a not radically removed lentigo maligna.

Interactions

The interaction between SOX10 and PAX3 is studied best in human patients with Waardenburg syndrome, an autosomal dominant disorder that 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. The two genes have binding sites near one another on the upstream enhancer of the c-RET gene. SOX10 is also thought to target dopachrome tautomerase through a synergistic interaction with MITF, which then results in other melanocyte alteration.

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

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.

See also

• SOX genes
• List of histologic stains that aid in diagnosis of cutaneous conditions

Further reading

• Jacobs JM, Wilson J (1992). "An unusual demyelinating neuropathy in a patient with Waardenburg's syndrome". Acta Neuropathol. 83 (6): 670–4. doi:10.1007/BF00299420. PMID 1636383.
• Southard-Smith EM, Kos L, Pavan WJ (1998). "Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model". Nat. Genet. 18 (1): 60–4. doi:10.1038/ng0198-60. PMID 9425902.
• Kuhlbrodt K, Schmidt C, Sock E, Pingault V, Bondurand N, Goossens M, Wegner M (1998). "Functional analysis of Sox10 mutations found in human Waardenburg-Hirschsprung patients". J. Biol. Chem. 273 (36): 23033–8. doi:10.1074/jbc.273.36.23033. PMID 9722528.
• Pusch C, Hustert E, Pfeifer D, Südbeck P, Kist R, Roe B, Wang Z, Balling R, Blin N, Scherer G (1998). "The SOX10/Sox10 gene from human and mouse: sequence, expression, and transactivation by the encoded HMG domain transcription factor". Hum. Genet. 103 (2): 115–23. doi:10.1007/s004390050793. PMID 9760192.
• Inoue K, Tanabe Y, Lupski JR (1999). "Myelin deficiencies in both the central and the peripheral nervous systems associated with a SOX10 mutation". Ann. Neurol. 46 (3): 313–8. doi:10.1002/1531-8249(199909)46:3<313::AID-ANA6>3.0.CO;2-7. PMID 10482261.
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
• Touraine RL, Attié-Bitach T, Manceau E, Korsch E, Sarda P, Pingault V, Encha-Razavi F, Pelet A, Augé J, Nivelon-Chevallier A, Holschneider AM, Munnes M, Doerfler W, Goossens M, Munnich A, Vekemans M, Lyonnet S (2000). "Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain". Am. J. Hum. Genet. 66 (5): 1496–503. doi:10.1086/302895. PMC 1378013. PMID 10762540.
• Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, Wegner M, Goossens M (2000). "Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome". Hum. Mol. Genet. 9 (13): 1907–17. doi:10.1093/hmg/9.13.1907. PMID 10942418.
• Smit DJ, Smith AG, Parsons PG, Muscat GE, Sturm RA (2000). "Domains of Brn-2 that mediate homodimerization and interaction with general and melanocytic transcription factors". Eur. J. Biochem. 267 (21): 6413–22. doi:10.1046/j.1432-1327.2000.01737.x. PMID 11029584.
• Sham MH, Lui VC, Chen BL, Fu M, Tam PK (2001). "Novel mutations of SOX10 suggest a dominant negative role in Waardenburg-Shah syndrome". J. Med. Genet. 38 (9): 30e–30. doi:10.1136/jmg.38.9.e30. PMC 1734934. PMID 11546831.
• Rehberg S, Lischka P, Glaser G, Stamminger T, Wegner M, Rosorius O (2002). "Sox10 is an active nucleocytoplasmic shuttle protein, and shuttling is crucial for Sox10-mediated transactivation". Mol. Cell. Biol. 22 (16): 5826–34. doi:10.1128/MCB.22.16.5826-5834.2002. PMC 133963. PMID 12138193.
• Pingault V, Girard M, Bondurand N, Dorkins H, Van Maldergem L, Mowat D, Shimotake T, Verma I, Baumann C, Goossens M (2002). "SOX10 mutations in chronic intestinal pseudo-obstruction suggest a complex physiopathological mechanism". Hum. Genet. 111 (2): 198–206. doi:10.1007/s00439-002-0765-8. PMID 12189494.
• Lang D, Epstein JA (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.
• Shimotake T, Tomiyama H, Aoi S, Iwai N (2003). "Discrepancy between macroscopic and microscopic transitional zones in Hirschsprung's disease with reference to the type of RET/GDNF/SOX10 gene mutation". J. Pediatr. Surg. 38 (5): 698–701. doi:10.1016/jpsu.2003.50186. PMID 12720173.
• Chan KK, Wong CK, Lui VC, Tam PK, Sham MH (2003). "Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation". J. Cell. Biochem. 90 (3): 573–85. doi:10.1002/jcb.10656. PMID 14523991.
• Inoue K, Khajavi M, Ohyama T, Hirabayashi S, Wilson J, Reggin JD, Mancias P, Butler IJ, Wilkinson MF, Wegner M, Lupski JR (2004). "Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations". Nat. Genet. 36 (4): 361–9. doi:10.1038/ng1322. PMID 15004559.

External links

• SOX10+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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