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FLASH GENE
Symbol SP7 contributors: mct/pgu - updated : 10-01-2024
HGNC name Sp7 transcription factor
HGNC id 17321
Corresponding disease
OIXII osteogenesis imperfecta type XII
Location 12q13.13      Physical location : 53.720.361 - 53.730.004
Synonym name
  • osterix
  • zinc finger protein osterix
  • osteoblast-specific transcription factor
    • Synonym symbol(s) OSX, MGC126598, osterix, OI11, OI12
    DNA
    TYPE functioning gene
    STRUCTURE 9.64 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure
  • Sp1 binding sites
  • exon 2 containing most of the protein coding sequence
    • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 splicing 2995 44.9 431 - 2007 17352693
    - splicing 3211 - 413 - 2003 14604442
    3 - 3123 - 431 - 2022 35628456
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/Equilibriumearinnercochlea  
    Nervousnervecranial nerve   
    Skeleton      Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveboneperiosteum   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificchondrocyte Homo sapiens
    Skeletonosteoblast Homo sapiens
    cell lineage specifically expressed in osteoblast lineage cells and, at lower levels, in prehypertrophic chondrocytes
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text in osteoblasts and osteocytes of all developing bones
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a buttonhead (BTD) box CXCPXC, just N-terminal to the zinc fingers
  • DNA binding domain of three C2H2-type zinc fingers
  • serine/threonine protein kinase catalytic domain
  • a transactivation domain containing high proline and glycine residues and having an activation property in mammalian cells at the
    • C terminus (C terminal region the DNA-binding domain which can bind to specific GC-rich sequences to control target gene expression, such as osteoblast differentiation markers type 1 collagen, bone sialoprotein, and BGLAP
    HOMOLOGY
    interspecies homolog to murine Osx
    Homologene
    FAMILY
  • Sp/KLF (Kruppel like Factor) family of transcription factors
  • C2H2-type zinc-finger protein family
    • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • required for osteoblast differentiation and bone formation, and inhibits Wnt pathway activity
  • promotes proliferation of mesenchymal cells
  • playing a role in the segregation of osteoblasts from osteochondro-progenitors
  • bone transcription factor which has nuclear localization
    • in the activated form, acting on downstream of RUNX2
  • possesses functional domains which associate with transcription mediated factors and functions as a transcriptional activator in the nucleus
  • enhances proliferation and osteogenic potential of bone marrow stromal cells
  • bone-related transcription factor that functions genetically downstream of RUNX2, which controls both growth and differentiation in osteoblasts
  • its expression inhibits bone morphogenetic protein-induced chondrogenic differentiation of mesenchymal progenitor cells
  • negatively regulates Wnt/beta-catenin signaling and osteoblast proliferation
  • differential biological functions of RUNX2, SP7, and DSPP during odontogenesis and osteogenesis
  • regulated via both RUNX2-dependent and -independent mechanisms, and controls osteoblast differentiation, at least in part, by regulating the expression of genes not controlled by RUNX2
  • required to maintain osteoblast function following adult bone maintenance
  • promotes the expression of the collagen gene, COL5A3, and thereby playing a role in bone formation
  • responsible for activation of the COL5A3 gene rather than Sp1
  • may be involved in regulating the COL5A3 gene in osteoblastic cells
  • participate in the activation of the COL5A3 promoter during osteoblast differentiation
  • essential multifunctional player in postnatal bone growth and homeostasis
  • may be acting as an essential and central factor of bone homeostasis after birth, because it is required not only for new bone formation, osteocyte maturation, and function, but also for cartilage resorption
  • critical transcription factor required for the maturation and function of osteocytes
  • osteoblast-specific transcription factor required for osteoblast differentiation and bone formation
  • involved in chondrogenic gene activation and is a positive regulator of the chondrocyte differentiation
  • upstream regulator of SATBb2 during bone formation
  • regulatory link between SP7 an SATB2, two important transcription factors, during bone formation
  • essential for osteoblast differentiation and bone formation in bone homeostasis
  • essential transcription factor required for osteoblast differentiation during both intramembranous and endochondral ossification
  • regulates chondrocyte differentiation and bone growth in growth plate chondrocytes, suggesting an autonomous function of SP7 in chondrocytes during endochondral ossification
  • regulates chondrocyte differentiation during endochondral ossification and thus has critical functions in chondrocytes as well as osteoblasts
  • controls DKK1 expression should further reinforce the feedback control effect that DKK1 exerts on WNT/CTNNB1 signaling
  • BMP2 inducible osteoblast-specific transcription factor required for osteoblast differentiation and bone formation
  • SP7 and and HIF1A cooperatively regulate VEGFA expression
  • essential transcription factor for endochondral ossification that functions downstream of RUNX2
  • positive regulator of chondrocyte differentiation
  • plays an essential role in osteoblast differentiation and bone formation
  • is an unstable protein, and the ubiquitin-proteasome pathway is involved in the regulation of OSX and thereby regulates osteoblast differentiation
  • is likely responsible for phenotypic conversion of Meckel chondrocytes during its degeneration
  • is not required for tooth morphogenesis but is obligatory for the functional maturation of both ameloblasts and odontoblasts
  • SP7 limits cranial bone initiation sites and is required for formation of sutures
  • is a key transcriptional determinant of bone-secreting osteoblasts
  • is an essential transcription factor for osteoblast differentiation
  • is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts
  • involved in regulation of osteoblast differentiation with RUNX2 and other factors such as ATF4
  • SP7 is involved in chondrocyte differentiation and osteocyte biology as well as postnatal bone metabolism
  • SP7 plays a conserved biological role in oligodendrocytes and in bone-forming cells, where it mediates brain and bone tissue stiffness by controlling expression of ECM components
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
  • RUNX2-NFIC-SP7 pathway is one of the key factors that regulate ameloblast differentiation
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • RUNX2
  • SOX9 and SOX5 (negative regulator)
  • RNA helicase A might act as a component of an
    • Osterix binding complex
  • interacting with SMARCD3 and SMARCA4, through its C-terminal zinc finger domain
  • interacting with DLX5 (binds and activates the osterix promoter, and mediates BMP2 induced Osterix expression)
  • bound to and activated the DKK1 promoter
  • interacting with C14orf169 which inbits SP7-mediated promoter activation
  • interacted with the COL5A3 core promoter
  • physical association of SP7 with SOST promoter (new additional mechanism through which SP7 inhibits Wnt signaling during bone formation)
  • controls SATB2 expression (bound to the SATB2 promoter sequence directly)
  • could act via the non-canonical Sp1/Sp3-binding element to regulate BGLAP transcription
  • is a direct transcriptional regulator with repressive effect on NELL1 gene expression, contributing to a delicate balance of regulatory effects on NELL1 transcription with RUNX2, and may play a crucial role in osteoblast differentiation and mineralization
  • is regulated by ERK1/2 in BMP2-induced osteoblast differentiation, and ERK1/2 modulates SP7 function by regulating protein stability and transcriptional activity
  • DKK1 is a direct target of SP7
  • controls VEGFA expression in osteoblasts, and SP7 regulation of VEGFA is independent of HIF1A expression level 6)
  • synthesis of FN1 is mediated by a transcriptional complex consisting of NFATC1, SP7 and FOS
  • physical and functional interaction between Osterix and RUNX2 were necessary for the induction of MMP13 during endochondral ossification
  • inducing COL1A1 gene expression through binding to SP1 sites in the bone enhancer and proximal promoter regions
  • direct regulatory role for SP7 in MMP13 gene expression in osteoblasts
  • is a novel target of CAMK2A and the activity of Osterix can be modulated by a novel mechanism involving CAMK2A during osteoblast differentiation
  • GSK3A regulates osteogenic activity of SP7
  • KDM6B plays important roles in osteoblast differentiation and regulates the expressions of IBSP and BGLAP via transcription factors RUNX2 and SP7
  • FBLN1 is required for bone formation and BMP2-mediated induction of SP7
  • RUNX2 and SP7 interact physically and functionally, and stimulate osteocalcin (OC)-promoter activity by 3-folds in epithelial cells
  • DLX recruitment of SP7 to osteoblast enhancers underlies SP7-directed osteoblast specification
  • FBN2 and POSTN will be target candidates of SP7 in osteoblast differentiation
  • SIRT7 has a critical role in bone formation by regulating acylation of SP7
  • role for SP7 and its target gene OSTN in osteocytogenesis, revealing that pathways that control osteocyte development influence human bone diseases
  • ZBTB16 may play an important role in modulating the odontoblastic differentiation of dental pulp stem cells (DPSCs) and act as a regulator of SP7
  • IHH in SP7-expressing cells plays an indispensable role in osteoblast differentiation, mineralization, and embryonic osteogenesis
    • cell & other
    REGULATION
    activated by BMP through the induction of DLX5 and its further transcriptional activation by p38-mediated phosphorylation
    BMP2, that increases the protein level of Osterix in an AKT1 activity-dependent manner
    induced by BMP2 in a mesenchymal cell line
    RUNX2 (RUNX2 induces SP7 expression, and RUNX2, SP7, and canonical Wnt signaling are required for the differentiation of preosteoblasts to immature osteoblasts)
    Phosphorylated by MAPK14, and Ser-73 and Ser-77 are the regulatory sites phosphorylated by MAPK14
    AKT1 (AKT1 phosphorylates Osterix and AKT1 activation increases protein stability, osteogenic activity and transcriptional activity of SP7)
    Other protein palmitoylation plays an important role in BMP-induced MAPK activation, SP7 expression, and osteoblast differentiation
    ERK1/2 regulates a major transcription factor, SP7, during osteoblast differentiation by increasing its protein stability and transcriptional activity
    ASSOCIATED DISORDERS
    corresponding disease(s) OIXII
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in expression of osteogenesis-related transcription factors RUNX2 and Osterix by TGFB3 induction of adipose-derived stromal cells during chondrogenesis
    constitutional     --over  
    significantly increased the promoter activity and the endogenous mRNA level of the COL5A3 gene in osteoblastic cells
    constitutional germinal mutation deletion    
    a homozygous single base pair deletion (c.1052delA) in a recessive osteogenesis imperfecta
    constitutional        
    dampened characteristic mineralization and lipid vacuole formation, respectively, and SP7 silencing affects the trilineage differentiation of bone marrow stromal cells (BMSC), but is insufficient to decouple BMSC hypertrophy from chondrogenesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • marker gene required for craniofacial bone formation by cranial neural crest-derived cells
    • Therapy target
    ANIMAL & CELL MODELS
  • Osx-null mutant mice, which die at birth, develop a complete cartilaginous skeleton, but no bone formation takes place in either the endochondral or membranous skeleton
  • Ihh ablation in Sp7-expressing cells of mice resulted in a dwarfism phenotype with severe skeletal dysplasia and lethality at birth, but with normal joint segmentation