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SOX10 (SRY (sex determining region Y)-box 10)

Written2010-04Michael Wegner
Institut fuer Biochemie, Emil-Fischer-Zentrum, Universitaet Erlangen-Nuernberg, 91054 Erlangen, Germany

(Note : for Links provided by Atlas : click)

Identity

Alias_namesmouse
human homolog of
Alias_symbol (synonym)DOM
WS4
WS2E
Other aliasMGC15649
HGNC (Hugo) SOX10
LocusID (NCBI) 6663
Atlas_Id 43768
Location 22q13.1  [Link to chromosome band 22q13]
Location_base_pair Starts at 38368319 and ends at 38380539 bp from pter ( according to hg19-Feb_2009)  [Mapping SOX10.png]
Local_order Flanked by POLR2F (DNA-directed RNA polymerase II polypeptide F) and PICK1 (protein interacting with PRKCA 1).
Fusion genes
(updated 2016)
PRR14L (22q12.2) / SOX10 (22q13.1)SOX10 (22q13.1) / FAM168A (11q13.4)

DNA/RNA

Note SOX10 was first identified as a gene mutated in patients suffering from Waardenburg syndrome type 4C (WS4C). SOX10 mutations also cause Waardenburg syndrome type 2E (WS2E) with or without neurologic involvement, Yemenite deaf-blind hypopigmentation syndrome and PCWH syndrome. They usually occur in the heterozygous state and can be either sporadic or familial.
 
  The SOX10 gene with its 5 exons. The open reading frame (orange) is split between exons 3-5. The 5' untranslated region is generated from exons 1-3 and the 3' untranslated region corresponds to the hind part of exon 5.
Description DNA size: 12.22kb; 5 Exons.
Transcription mRNA size: 2882 nucleotides.

Protein

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.
 
  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).
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.

Mutations

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.

Implicated in

Note
  
Entity Melanoma
Note SOX10 is expressed homogenously in primary and metastatic melanoma and was identified as a melanoma tumor antigen. It is often co-expressed with its relative SOX9. Somatic SOX10 mutations occur in early stage melanoma. SOX10 upregulates MITF, MET and Nestin expression in melanoma and responds to Wnt signals. Its nuclear localization is controlled by the Tam tyrosine receptor kinase Tyro3 and its activity is modulated by the transcription factor SOX5. In sentinel lymph nodes, SOX10 is a reliable marker for metastatic melanoma.
  
  
Entity Clear cell sarcoma
Note SOX10 is widely expressed in clear cell sarcoma where it cooperates with EWS-ATF1 fusions in MITF activation.
  
  
Entity Malignant nerve sheath tumor (MNST)
Note SOX10 is present in MNST. Expression levels appear lower than the ones in plexiform neurofibromas from which MNST arise or in Schwann cells. SOX10 expression levels are positively correlated with ErbB3 levels and inversely correlated with SOX9 levels.
  
  
Entity Schwannoma
Note Homogenous SOX10 expression has been detected throughout this neoplasm.
  
  
Entity Ganglioneuroma
Note SOX10 expression has been detected. Levels decrease with increasing grade.
  
  
Entity Glioma
Note SOX10 transcripts and protein were found in astrocytoma, oligodendroglioma and glioblastoma. Expression levels and number of expressing cells within the tumor usually diminish with advancing grade and malignant progression. SOX10 levels are particularly high in pilocytic astrocytoma. No correlation with 1p and 19q deletions has been detected. In a mouse model, SOX10 has been found to act synergistically with PDGF during glioma development, although it was not sufficient to induce gliomagenesis on its own.
  

Bibliography

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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
Sorting out Sox10 functions in neural crest development.
Kelsh RN.
Bioessays. 2006 Aug;28(8):788-98. (REVIEW)
PMID 16927299
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 

Citation

This paper should be referenced as such :
Wegner, M
SOX10 (SRY (sex determining region Y)-box 10)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(1):65-67.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SOX10ID43768ch22q13.html


Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ]
  Waardenburg syndrome (WS)


External links

Nomenclature
HGNC (Hugo)SOX10   11190
LRG (Locus Reference Genomic)LRG_271
Cards
AtlasSOX10ID43768ch22q13
Entrez_Gene (NCBI)SOX10  6663  SRY-box 10
AliasesDOM; PCWH; WS2E; WS4; 
WS4C
GeneCards (Weizmann)SOX10
Ensembl hg19 (Hinxton)ENSG00000100146 [Gene_View]  chr22:38368319-38380539 [Contig_View]  SOX10 [Vega]
Ensembl hg38 (Hinxton)ENSG00000100146 [Gene_View]  chr22:38368319-38380539 [Contig_View]  SOX10 [Vega]
ICGC DataPortalENSG00000100146
TCGA cBioPortalSOX10
AceView (NCBI)SOX10
Genatlas (Paris)SOX10
WikiGenes6663
SOURCE (Princeton)SOX10
Genetics Home Reference (NIH)SOX10
Genomic and cartography
GoldenPath hg19 (UCSC)SOX10  -     chr22:38368319-38380539 -  22q13.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)SOX10  -     22q13.1   [Description]    (hg38-Dec_2013)
EnsemblSOX10 - 22q13.1 [CytoView hg19]  SOX10 - 22q13.1 [CytoView hg38]
Mapping of homologs : NCBISOX10 [Mapview hg19]  SOX10 [Mapview hg38]
OMIM602229   609136   611584   613266   
Gene and transcription
Genbank (Entrez)AJ001183 AK300945 AK310896 BC002824 BC007595
RefSeq transcript (Entrez)NM_006941
RefSeq genomic (Entrez)NC_000022 NC_018933 NG_007948 NT_011520 NW_004929430
Consensus coding sequences : CCDS (NCBI)SOX10
Cluster EST : UnigeneHs.376984 [ NCBI ]
CGAP (NCI)Hs.376984
Alternative Splicing GalleryENSG00000100146
Gene ExpressionSOX10 [ NCBI-GEO ]   SOX10 [ EBI - ARRAY_EXPRESS ]   SOX10 [ SEEK ]   SOX10 [ MEM ]
Gene Expression Viewer (FireBrowse)SOX10 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)6663
GTEX Portal (Tissue expression)SOX10
Protein : pattern, domain, 3D structure
UniProt/SwissProtP56693   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP56693  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP56693
Splice isoforms : SwissVarP56693
PhosPhoSitePlusP56693
Domaine pattern : Prosite (Expaxy)HMG_BOX_2 (PS50118)   
Domains : Interpro (EBI)HMG_box_dom    Sox_N   
Domain families : Pfam (Sanger)HMG_box (PF00505)    Sox_N (PF12444)   
Domain families : Pfam (NCBI)pfam00505    pfam12444   
Domain families : Smart (EMBL)HMG (SM00398)  
Conserved Domain (NCBI)SOX10
DMDM Disease mutations6663
Blocks (Seattle)SOX10
SuperfamilyP56693
Human Protein AtlasENSG00000100146
Peptide AtlasP56693
HPRD03752
IPIIPI00010781   IPI00908479   IPI00853081   
Protein Interaction databases
DIP (DOE-UCLA)P56693
IntAct (EBI)P56693
FunCoupENSG00000100146
BioGRIDSOX10
STRING (EMBL)SOX10
ZODIACSOX10
Ontologies - Pathways
QuickGOP56693
Ontology : AmiGORNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II distal enhancer sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II transcription factor binding  in utero embryonic development  neural crest cell migration  positive regulation of neuroblast proliferation  chromatin binding  transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding  transcription coactivator activity  protein binding  nucleus  nucleus  nucleoplasm  regulation of transcription from RNA polymerase II promoter  transcription from RNA polymerase II promoter  peripheral nervous system development  transcription factor binding  anatomical structure morphogenesis  positive regulation of gliogenesis  melanocyte differentiation  extrinsic component of mitochondrial outer membrane  lacrimal gland development  identical protein binding  negative regulation of apoptotic process  negative regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  cell maturation  enteric nervous system development  digestive tract morphogenesis  developmental growth  oligodendrocyte differentiation  morphogenesis of a branching epithelium  negative regulation of canonical Wnt signaling pathway  
Ontology : EGO-EBIRNA polymerase II core promoter proximal region sequence-specific DNA binding  RNA polymerase II distal enhancer sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II transcription factor binding  in utero embryonic development  neural crest cell migration  positive regulation of neuroblast proliferation  chromatin binding  transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding  transcription coactivator activity  protein binding  nucleus  nucleus  nucleoplasm  regulation of transcription from RNA polymerase II promoter  transcription from RNA polymerase II promoter  peripheral nervous system development  transcription factor binding  anatomical structure morphogenesis  positive regulation of gliogenesis  melanocyte differentiation  extrinsic component of mitochondrial outer membrane  lacrimal gland development  identical protein binding  negative regulation of apoptotic process  negative regulation of transcription, DNA-templated  positive regulation of transcription from RNA polymerase II promoter  cell maturation  enteric nervous system development  digestive tract morphogenesis  developmental growth  oligodendrocyte differentiation  morphogenesis of a branching epithelium  negative regulation of canonical Wnt signaling pathway  
NDEx NetworkSOX10
Atlas of Cancer Signalling NetworkSOX10
Wikipedia pathwaysSOX10
Orthology - Evolution
OrthoDB6663
GeneTree (enSembl)ENSG00000100146
Phylogenetic Trees/Animal Genes : TreeFamSOX10
HOVERGENP56693
HOGENOMP56693
Homologs : HomoloGeneSOX10
Homology/Alignments : Family Browser (UCSC)SOX10
Gene fusions - Rearrangements
Fusion : MitelmanPRR14L/SOX10 [22q12.2/22q13.1]  [t(22;22)(q12;q13)]  
Fusion : MitelmanSOX10/FAM168A [22q13.1/11q13.4]  [t(11;22)(q13;q13)]  
Fusion: TCGAPRR14L 22q12.2 SOX10 22q13.1 HNSC
Fusion: TCGASOX10 22q13.1 FAM168A 11q13.4 LGG
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSOX10 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SOX10
dbVarSOX10
ClinVarSOX10
1000_GenomesSOX10 
Exome Variant ServerSOX10
ExAC (Exome Aggregation Consortium)SOX10 (select the gene name)
Genetic variants : HAPMAP6663
Genomic Variants (DGV)SOX10 [DGVbeta]
DECIPHER (Syndromes)22:38368319-38380539  ENSG00000100146
CONAN: Copy Number AnalysisSOX10 
Mutations
ICGC Data PortalSOX10 
TCGA Data PortalSOX10 
Broad Tumor PortalSOX10
OASIS PortalSOX10 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSOX10  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSOX10
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
BioMutasearch SOX10
DgiDB (Drug Gene Interaction Database)SOX10
DoCM (Curated mutations)SOX10 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SOX10 (select a term)
intoGenSOX10
NCG5 (London)SOX10
Cancer3DSOX10(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602229    609136    611584    613266   
Orphanet17538    220    959    3249   
MedgenSOX10
Genetic Testing Registry SOX10
NextProtP56693 [Medical]
TSGene6663
GENETestsSOX10
Huge Navigator SOX10 [HugePedia]
snp3D : Map Gene to Disease6663
BioCentury BCIQSOX10
ClinGenSOX10 (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD6663
Chemical/Pharm GKB GenePA36027
Clinical trialSOX10
Miscellaneous
canSAR (ICR)SOX10 (select the gene name)
Probes
Litterature
PubMed114 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSOX10
EVEXSOX10
GoPubMedSOX10
iHOPSOX10
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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