Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol SOX6 contributors: shn/npt/pgu - updated : 01-09-2020
HGNC name SRY (sex determining region Y)-box 6
HGNC id 16421
DNA
TYPE functioning gene
SPECIAL FEATURE arranged in tandem
STRUCTURE 772.03 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
Binding site   HRE
text structure
  • PS4A identified as an essential complex regulatory element containing SOX binding site
  • lacked the TATA box, instead containing a GC rich sequence
  • a core enhancer CES6
  • negative SOX6 autoregulation, mediated by the double SOX6 binding site within its own promoter, may be relevant to control the SOX6 transcriptional downregulation (
    • MAPPING cloned Y linked N status provisional
    Map pter - D11S4121 - D11S1791 - SOX6 - D11S4099 - D11S4160 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 splicing 8919 - 841 - 2001 11255018
  • isoform 4
    • 16 splicing 8865 - 808 - 2001 11255018
    15 splicing 8979 - 804 - 2001 11255018
    15 - 8957 - 809 - 2001 11255018
    15 - 9037 - 787 - 2001 11255018
    16 - 9304 - 828 - 2001 11255018
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
    Nervousbrainmidbrainsubstantia nigra   Homo sapiens
     brainlimbic systemhippocampus highly Homo sapiensFetal
     braindiencephalonamygdala   Homo sapiensFetal
    Urinarykidneyjuxtaglomerulus apparatus  highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Muscularstriatumskeletal highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text
  • developing nervous system
  • coexpression of SHOX, SOX5, SOX6 and SOX9 in the fetal growth plate
    • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two putative coiled-coil domains
  • a high mobility group box DNA binding domain, HMG domain, interacting with SHOX
    • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies ortholog to Sox6, Mus musculus
    ortholog to sox6, Danio rerio
    ortholog to Sox6, Ratus norvegicus
    Homologene
    FAMILY
  • D subfamily of sex determining region y-related transcription factors
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • transcriptional activator
  • required for normal development of the central nervous system, chondrogenesis and maintenance of cardiac and skeletal muscle cells
  • essential for endochondral skeleton formation
  • plays key functions in several developmental processes, including neurogenesis and skeleton formation
  • regulates several stages of oligodendrocyte development in spinal cord
  • regulates multiple aspects of cortical interneuron differentiation, ultimately controlling the molecular diversity of cortical interneuron subtypes
  • a central regulator of both progenitor and cortical interneuron diversity during neocortical development
  • a role in roles in the generation of neuronal diversity during neocortical development
  • redundantly enhance chondrogenesis, but retard gliogenesis, and promotes erythropoiesis
  • enhance transactivation by SOX9 in chondrocytes, but antagonize SOX9 and other SoxE proteins in oligodendrocytes and melanocytes, and also repress transcription through various mechanisms in several other lineages
  • enhances erythroid differentiation in human erythroid progenitors
  • plays an essential role in coordinating muscle fiber type differentiation by acting as a transcriptional suppressor of slow fiber-specific genes
  • SOX8 expression is regulated by SOX9, and both together with SOX5 and SOX6 are required as a SOX quartet for transcription of COL2A1 and a large number of other chondrogenic molecules
  • SOX6 and OTX2 control the specification of substantia nigra and ventral tegmental area dopamine neurons
  • SOX6 and RUNX2 play essential roles in the communication of chondrocyte and osteoblast
  • novel function of SOX6 and RUNX2 in the endochondral ossification
  • transcription factor that is crucial for the differentiation and development of cortical interneurons and dopaminergic neurons of the substantia nigra pars compact
  • SOX9 and SOX5/SOX6 thus cooperate genome-wide, primarily through super-enhancers (SEs), to implement the growth plate chondrocyte differentiation program
  • transcription factors SOX5 and SOX6 exert direct and indirect influences on oligodendroglial migration in spinal cord and forebrain
  • SOX9 (SOXE group) is essential for chondrocyte fate maintenance and differentiation, and works in cooperation with SOX5 and SOX6 (SOXD group) and other types of transcription factors
  • role for SOX6 in renin expression
  • has important roles in several regions of the developing human brain
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS nervous system
    PATHWAY
    metabolism
    signaling
    a component
  • SOX6 and others SOX (combination of SOX9, SOX5, and SOX6, the SOX trio), but not SOX9 alone, potently stimulated the chondrogenic differentiation of the non-chondrogenic cells such as the dermal fibroblasts
    • INTERACTION
    DNA binding specifically to the sequence 5'-AACAAT-3'
    RNA
    small molecule
    protein
  • SRY (sex determining region Y)-box 5, SOX5
  • soxLZ/Sox6-binding protein Solt
  • C-terminal binding protein 2, CTBP2
  • DAZ associated protein 2, DAZAP2
  • interacting with BCL11A during erythroid maturation and cooperating in silencing gamma-globin transcription in adult erythroid progenitors
  • direct target gene of STAT3 (STAT3 is required for SOX6 expression during neuronal differentiation)
  • SOCS3 is a relevant SOX6 effector
  • SHOX cooperates with SOX5/SOX6 and SOX9 in the activation of the upstream ACAN enhancer
  • SOCS3 overexpression in primary erythroid cells recapitulated the growth inhibition induced by SOX6, which demonstrates that SOCS3 is a relevant SOX6 effector
  • ZAK plays an essential role in the onset of chondrogenesis through triggering the induction of SOX6 expression by SOX9
  • MKX regulating the transcription of MYH7 through repression of SOX6 which predicts a role in fiber type specificity
  • TRIP12, a HECT domain E3 ubiquitin ligase, recognizes and polyubiquitinates SOX6
  • SOX6 is a direct nuclear target of CDK5 (CDK5 regulates SOX6 steady state protein level that has an important role in brain development and function)
  • SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARG, CEBPA and MEST
  • SOX6 interact with the promoter of TWIST1, a helix-loop-helix transcription factor involved in the induction of EMT, and to modulate the expression of TWIST1 by recruiting HDAC1 to the promoter of the TWIST1 gene
    • cell & other
    REGULATION
    induced by SOX9
    repressed by SUMO modification
    Other SOX6 steady state levels are regulated by CDK5
    ASSOCIATED DISORDERS
    corresponding disease(s) TOLCAS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    rapid-onset dopa-responsive movement disorder, delayed development, and dysmorphic features
    tumoral     --low  
    decreased in hepatocellular carcinoma, which correlated with poor prognosis
    tumoral     --low  
    in patients with Pancreatic cancer (PC) in association with metastatic disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • for craniosynostosis
  • for myopathy
    • Marker
  • may be a novel and potential prognostic marker for hepatocellular carcinoma
    • Therapy target
    ANIMAL & CELL MODELS
  • Mice homozygous for mutant allele p(100H), which interrupt the p gene and the Sox6 gene, show delayed growth, develop progressive atrioventricular heart block, significant ultrastructural changes in both cardiac, skeletal muscle cells and die within 2 wk after birth
  • Sox6 single null mice are born with mild skeletal abnormalities
  • Sox5-Sox6 double null fetuses die with a severe, generalized chondrodysplasia
  • Sox6-deficient mice are anemic due to impaired red cell maturation and show inappropriate globin gene expression in definitive erythrocytes