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FLASH GENE
Symbol SP1 contributors: mct/npt/pgu - updated : 27-05-2016
HGNC name Sp1 transcription factor
HGNC id 11205
Location 12q13.13      Physical location : 53.773.978 - 53.810.224
Synonym name specificity protein 1
Synonym symbol(s) TSFP1
DNA
TYPE functioning gene
STRUCTURE 36.25 kb     6 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
Binding site   transcription factor
text structure
  • binding strongly to GC and GT-box regulatory elements
  • a GC rich region containing multiple GC box and AP2 binding site
  • Sp1 minimal promoter has been identified and it has two Sp1/Sp3 sites
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 7667 105 785 - 2009 19138671
  • SP1A
  • 6 - 7614 - 778 - 2009 19138671
    SP1B
    - splicing - - 737 ubiquitously expressed 2011 21798247
  • lacks 48 AAs in the inhibitory domain
  • displays higher transcriptional activity than wild-type SP1
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a long serine/threonine and glutamine rich region (transactivation domain) at the N terminus
  • a button head (BTD) box CXCPXC, just N-terminal to the zinc fingers
  • 61 putative phosphorylation sites, with 48 of these residues being Ser, 10 Thr, and 3 Tyr
  • three tandem repeats of C2H2 zinc finger motif at C-terminus that specifically binds the target DNA (terms “GC box” element)and Sp1 must have NLSs to be imported into the nucleus
  • conjugated GlycoP
    mono polymer polymer
    HOMOLOGY
    interspecies homolog to C.elegans R13h8.1
    homolog to rattus Sp1 (96,56 pc)
    homolog to murine Sp1 (95,78 pc)
    Homologene
    FAMILY
  • Sp1 C2H2-type zinc-finger protein family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,chromatin/chromosome
    intracellular,nucleus,nucleolus
    text
  • localized in the nucleus and regulates gene expression
  • centrosomal protein
  • can be transported into the nucleus in an importin-dependent manner
  • basic FUNCTION
  • transcriptional activator, binding to GC box promoters elements and selectively activates mRNA synthesis from genes that contain functional recognition sites
  • can interact with G/C-rich motifs from serotonin receptor promoter
  • transcriptional activation of FLNA
  • involved in regulating the development of pituitary gland and nervous system
  • implicated in the regulation of genes that control multiple cellular processes, including cell cycle, apoptosis, and DNA damage
  • involved in the control of centrosome number via regulation of the MTOR pathway
  • regulating the Lhx4 promoter, binding to GC boxes
  • act as copper-sensing transcriptional activator to regulate prion gene expression
  • SP1 zinc finger known as the DNA binding domain plays a role as a NLS, and the properly folded secondary structure of the zinc finger is required for this function
  • GATA2 and SP1 positively regulate the c-kit promoter in mast cells
  • transcription factor SP1 and SP3 up-regulate the basal transcriptional activity of CD2AP and increase CD2AP expression at mRNA level
  • essential transcription factor required for SP7 recruitment and transactivation of the BGLAP promoter
  • SP1 and TP53 influence cell proliferation and differentiation and similar biological processes in both dental pulp stem cells and dental follicle cells
  • SP1, NFYC and FOXO3, FOXO4 transcription factors are involved in the regulation of STK11 transcription
  • SP1 is an important transcription factor that regulates proliferation and survival of Waldenström macroglobulinemia (WM) cells independent of MYD88 pathway activation
  • is a pivotal transcription factor for the regulation of CEP131 expression, consequently leading the control of centrosome functions
  • essential, and finely tuned role for SP1 in adipose lineage differentiation in human mesenchymal stem cells
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • tertiary structure formed by the three zinc fingers is essential for nuclear localization as well as dispersed basic amino acids within the zinc fingers region
  • INTERACTION
    DNA binding strongly to GC and GT-box regulatory elements
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • PSMC5-leading to proteasome-dependent degradation of SP1, AP2
  • TAF4 and HO
  • functional synergy of SP1, SP3, SP4 with the photoreceptor-enriched CRX transcriptional regulator on the rod opsin promoter but not the beta-PDE promoter, although SP4-mediated activation was the most significant
  • interacts with POGZ, HCFC1, AATF and PHC2
  • interacts with varicella-zoster virus ie62 protein and HIV-1 vpr
  • interacting with FGFR1 (necessary positive regulator of FGFR1 gene transcription in neonatal cardiomyocytes)
  • interacting with ZBTB2
  • binds GC-rich motifs with high affinity and can regulate the expression of TATA-containing and TATA-less genes via protein-protein interactions or interplay with other transcription factors such as Ets-1, c-myc, c-Jun, Stat1 and Egr-1
  • CDX2 and SP1 can activate the ELMO3 promoter
  • CREB1, SP1, and TFAP4 play roles in modulating PPP2R2B expression
  • direct interaction with the transport factor importin alpha, not importin beta (SP1 requires all three zinc finger for the nucleus localization, and it is indispensable in the interaction with importin alpha)
  • activates DOK7 gene expression through interaction with these two SP1 sites
  • critical regulator of the CTH expression during smooth muscle cells differentiation
  • plays an important role in regulation of Kindlin-2 (FERMT2) expression (PMI: 21922223)
  • PLAGL1 might serve as an SP1-like protein that directly interacts with the SP1-responsive element to oligomerize with and/or to coactivate SP1
  • bound to the CTSE promoter region, and SP1 binding plays potentially a particularly important role in the regulation of CTSE gene expression
  • promoter of SERPINA3 is transcriptionally activated by three transcription factors (TFs) (SP1, MZF1 and ZBTB7B)
  • binds to the MFN2 promoter and its overexpression activates the MFN2 promoter in vascular smooth muscle cells) (
  • is a major regulator of periodic expression of CKAP2, and cell-cycle-dependent phosphorylation of SP1 mediated by CCNA2 can regulate the DNA-binding affinity of SP1
  • basal expression level of IRF3 is regulated by transcription factors SP1 and SP3
  • crucial role of SP1 in the regulation of CEP131 gene transcription
  • interaction between accumulated preLMNA and SP1 transcription factor, results in altered extracellular matrix gene expression, impairing adipogenesis
  • NR1D1 activates GJA1 transcription by forming a complex with SP1
  • SP1 is a fundamental activator of basal SYN1 gene expression, whose activity is modulated by the neural master regulator REST and CpG methylation
  • strict functional interplay between SP1 and REST, which exerts a dominant negative role on SP1 function and chromatin affinity on the SYN1 promoter
  • SP1 may significantly affect the number of EPOR molecules present on the surface of activated CD4(+) lymphocytes
  • FUT4 is a target gene for HSF1 and SP1 that is required for cell cycle progression in breast cancer epithelial cells
  • SP1 and SP3 are functionally involved as transcriptional integrators regulating the basal expression of the derived EPHX1 E1b variant transcript
  • SP1/SP3 transcription factors trigger MINA expression through additive activity targeted to a cluster of four SP1/SP3 binding sites forming the P1 promoter
  • EPAS1 plays an indispensible role in SP1 transcription factor-mediated ZBTB7A induction, and participated in tumor cell survival and proliferation
  • MALAT1 directly interacted with SP1 and LTBP3 promoter to increase expression of LTBP3 gene
  • CTCFL and Sp1 have opposite effects on the regulation of MAGEA1 gene expression
  • GATA2, SP1 and TATA-binding protein (TBP)interacting with the proximal promoter region of MAOA
  • SENP3 regulates the global protein turnover and the SP1 level via antagonizing SUMO2/3-targeted ubiquitination and degradation
  • SP1 transcription factor is the primary determinant for activating the basal transcription of the IRF5
  • cell & other
  • binding the interferon gamma responsive element and influencing the IFNG mediated suppression of macrophage lipoprotein lipase gene transcription
  • associating with the endogenously repressed TERT (telomerase reverse transcriptase) recruiting histone deacetylase(s) for the localized deacetylation of nucleosomal histones ans silencing of TERT in normal somatic cells
  • transactivating COL2A1 expression in chondrocyte, suppressed by SP3
  • its overexpression activated NME5 promoter activity in pancreatic cancer cells
  • REGULATION
    induced by SP1 (autoregulation)
    inhibited by O-linkage to N-acetylglucosamine (partially)
    cytokine (DNA binding activity)
    its interaction with ZBTB2
    Other dephosphorylated by PP1
    phosphorylated by MAPK14
    phosphorylation plays a role in the derecruitment of repressor proteins from the promoter
    sumoylated at the N terminus under basal conditions, which negatively regulates Sp1 transcriptional activity
    glycosylation can either stimulate or repress DNA binding and transcription
    acetylation appears to play a protective role in neuronal cells undergoing oxidative stress via elevated cyclooxygenase 2 (COX-2) expression
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    can lead to aberrant centriole splitting, deregulated MTOR signaling, and aneuploidy, thereby contributing to malignant transformation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascular  
    Sp1-induced MFN2 transcription may represent a mechanism for prevention of vascular smooth muscle cells proliferation and neointimal lesion and development
    ANIMAL & CELL MODELS
    Sp1-deficient mouse embryonic fibroblasts and cells depleted of SP1 by RNAi have increased centrosome number associated with centriole splitting, decreased microtubule nucleation, chromosome misalignment