Note | The SOX10 protein belongs to subgroup E of the SOX protein family. All 20 human members of this protein family possess a high-mobility-group (HMG) domain with three alpha-helical regions and close similarity to the one found in the male sex determining factor SRY. SOX10 functions as transcription factor and structural protein in chromatin. SOX9 and SOX8 are its closest relatives among human SOX proteins. |
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| Human SOX10 and its domains including the DNA-dependent dimerization domain (Dim), the DNA-binding HMG domain, the context-dependent transactivation domain K2 and the main transactivation domain (TA). Numbers indicate amino acid positions. The bottom shows the exact amino acid sequence of the HMG domain with its three alpha-helices, the 2 nuclear localization signals (NLS1, NLS2) and the nuclear export sequence (NES). |
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Description | SOX10 consists of 466 amino acids. The following domains exist (from amino terminal to carboxy terminal): DNA-dependent dimerization domain (amino acids 61-101), DNA-binding HMG-domain (amino acids 101-180), context-dependent transactivation domain K2 (amino acids 233-306) and main transactivation domain TA (amino acids 400-462). SOX10 possesses two nuclear localization signals (NLS) at the beginning and the end of the HMG domain and a nuclear export sequence (NES in the middle). |
Expression | SOX10 expression is first detected during embryonic development in the emerging neural crest and continues transiently or permanently in many non-ectomesenchymal derivates of the neural crest including melanocytes, adrenal medulla and the developing peripheral nervous system. Within the developing central nervous system SOX10 marks cells of the oligodendrocyte lineage. In the adult, SOX10 is predominantly found in oligodendrocytes, peripheral glial cells, melanocytes and adult neural crest stem cell populations. |
Localisation | SOX10 is predominantly found in the nucleus as expected for a transcription factor but possesses the ability to shuttle between cytoplasm and nucleus because of the presence of both NLS and NES in the protein. |
Function | SOX10 has multiple roles during development. In neural crest stem cells, SOX10 is needed for self-renewal, survival and maintenance of pluripotency. SOX10 is furthermore required for specification of melanocytes and peripheral glia from the neural crest. After specification, SOX10 continues to be essential for lineage progression and maintenance of identity in peripheral glia. Terminal differentiation of oligodendrocytes also depends on SOX10. SOX10 exerts these functions through interactions with different sets of transcription factors. SOX10 probably shares further roles with its close relatives SOX9 and SOX8 with which it is co-expressed in several cell types and functions in a partly redundant manner. |
Homology | SOX10 is highly conserved among vertebrates. Human SOX10 shares 98% identity with Mus musculus Sox10, 97% identity with Sox10 from Rattus norvegicus and Canis lupus familiaris, 96% identity with Bos taurus Sox10 and 82% identity with Gallus gallus Sox10. |
Note | SOX10 mutations have so far primarily been identified as a cause for neurocristopathies including WS4C, WS2E with or without neurologic involvement, PCWH syndrome and Yemenite deaf-bling hypopigmentation syndrome. |
Germinal | Missense mutations: S135T, A157V, Q174P. Nonsense mutations: R43X, T83X, T173X, E189X, T207X, Q234X, Q250X, S251X, T313X, S346X, Q364X, Q372X, S376X, Q377X. Insertions: (L160 R161) dup. Carboxy terminal extensions: X467C ext82, X467L ext86, X467T ext86. Frameshift mutations: S17C fsX17, E57S fsX57, A110L fsX2, P169R fsX117, R215P fsX64, R261A fsX25, G266A fsX20, I271S fsX15, H283L fsX11, H306T fsX5, G308A fsX3, V350C fsX52, A354P fsX3, E359D fsX42, Q399V fsX2. Splice mutations: int3 pos.428 +2T>G, int4 pos.698 -2A>C. |
Somatic | Missense mutations: R43Q, Q125X, A361V, G413S, G413D, H414Y, A424V. Frameshift mutations: P14P fsX10, S449S fsX66. |
Paired overexpression of ErbB3 and Sox10 in pilocytic astrocytoma. |
Addo-Yobo SO, Straessle J, Anwar A, Donson AM, Kleinschmidt-Demasters BK, Foreman NK. |
J Neuropathol Exp Neurol. 2006 Aug;65(8):769-75. |
PMID 16896310 |
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Oligodendroglial-specific transcriptional factor SOX10 is ubiquitously expressed in human gliomas. |
Bannykh SI, Stolt CC, Kim J, Perry A, Wegner M. |
J Neurooncol. 2006 Jan;76(2):115-27. |
PMID 16205963 |
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Diagnostic value of Sox10 immunohistochemical staining for the detection of metastatic melanoma in sentinel lymph nodes. |
Blochin E, Nonaka D. |
Histopathology. 2009 Nov;55(5):626-8. |
PMID 19912373 |
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Frequent mutations in the MITF pathway in melanoma. |
Cronin JC, Wunderlich J, Loftus SK, Prickett TD, Wei X, Ridd K, Vemula S, Burrell AS, Agrawal NS, Lin JC, Banister CE, Buckhaults P, Rosenberg SA, Bastian BC, Pavan WJ, Samuels Y. |
Pigment Cell Melanoma Res. 2009 Aug;22(4):435-44. Epub 2009 Apr 29. |
PMID 19422606 |
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Oncogenic MITF dysregulation in clear cell sarcoma: defining the MiT family of human cancers. |
Davis IJ, Kim JJ, Ozsolak F, Widlund HR, Rozenblatt-Rosen O, Granter SR, Du J, Fletcher JA, Denny CT, Lessnick SL, Linehan WM, Kung AL, Fisher DE. |
Cancer Cell. 2006 Jun;9(6):473-84. |
PMID 16766266 |
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Sox10 has a broad expression pattern in gliomas and enhances platelet-derived growth factor-B--induced gliomagenesis. |
Ferletta M, Uhrbom L, Olofsson T, Ponten F, Westermark B. |
Mol Cancer Res. 2007 Sep;5(9):891-7. |
PMID 17855658 |
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Temporally regulated neural crest transcription factors distinguish neuroectodermal tumors of varying malignancy and differentiation. |
Gershon TR, Oppenheimer O, Chin SS, Gerald WL. |
Neoplasia. 2005 Jun;7(6):575-84. |
PMID 16036108 |
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Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations. |
Inoue K, Khajavi M, Ohyama T, Hirabayashi S, Wilson J, Reggin JD, Mancias P, Butler IJ, Wilkinson MF, Wegner M, Lupski JR. |
Nat Genet. 2004 Apr;36(4):361-9. Epub 2004 Mar 7. |
PMID 15004559 |
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Sorting out Sox10 functions in neural crest development. |
Kelsh RN. |
Bioessays. 2006 Aug;28(8):788-98. (REVIEW) |
PMID 16927299 |
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The Waardenburg syndrome type 4 gene, SOX10, is a novel tumor-associated antigen identified in a patient with a dramatic response to immunotherapy. |
Khong HT, Rosenberg SA. |
Cancer Res. 2002 Jun 1;62(11):3020-3. |
PMID 12036907 |
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PAX3 and SOX10 activate MET receptor expression in melanoma. |
Mascarenhas JB, Littlejohn EL, Wolsky RJ, Young KP, Nelson M, Salgia R, Lang D. |
Pigment Cell Melanoma Res. 2010 Apr 1;23(2):225-37. Epub 2010 Jan 22. |
PMID 20067553 |
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The importance of having your SOX on: role of SOX10 in the development of neural crest-derived melanocytes and glia. |
Mollaaghababa R, Pavan WJ. |
Oncogene. 2003 May 19;22(20):3024-34. (REVIEW) |
PMID 12789277 |
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Sox10: a pan-schwannian and melanocytic marker. |
Nonaka D, Chiriboga L, Rubin BP. |
Am J Surg Pathol. 2008 Sep;32(9):1291-8. |
PMID 18636017 |
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SOX10 mutations in patients with Waardenburg-Hirschsprung disease. |
Pingault V, Bondurand N, Kuhlbrodt K, Goerich DE, Prehu MO, Puliti A, Herbarth B, Hermans-Borgmeyer I, Legius E, Matthijs G, Amiel J, Lyonnet S, Ceccherini I, Romeo G, Smith JC, Read AP, Wegner M, Goossens M. |
Nat Genet. 1998 Feb;18(2):171-3. |
PMID 9462749 |
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From stem cells to neurons and glia: a Soxist's view of neural development. |
Wegner M, Stolt CC. |
Trends Neurosci. 2005 Nov;28(11):583-8. Epub 2005 Aug 31. (REVIEW) |
PMID 16139372 |
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A genomic screen identifies TYRO3 as a MITF regulator in melanoma. |
Zhu S, Wurdak H, Wang Y, Galkin A, Tao H, Li J, Lyssiotis CA, Yan F, Tu BP, Miraglia L, Walker J, Sun F, Orth A, Schultz PG, Wu X. |
Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17025-30. Epub 2009 Sep 23. |
PMID 19805117 |
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