ID:SP1_HUMAN DESCRIPTION: RecName: Full=Transcription factor Sp1; FUNCTION: Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. Binds with high affinity to GC-rich motifs and regulates the expression of a large number of genes involved in a variety of processes such as cell growth, apoptosis, differentiation and immune responses. Highly regulated by post-translational modifications (phosphorylations, sumoylation, proteolytic cleavage, glycosylation and acetylation). Binds also the PDGFR- alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. SUBUNIT: Interacts with ATF7IP, ATF7IP2, BAHD1, POGZ, HCFC1, AATF and PHC2. Interacts with varicella-zoster virus IE62 protein. Interacts with HIV-1 Vpr; the interaction is inhibited by SP1 O- glycosylation. Interacts with SV40 VP2/3 proteins. Interacts with SV40 major capsid protein VP1; this interaction leads to a cooperativity between the 2 proteins in DNA binding. Interacts with HLTF; the interaction may be required for basal transcriptional activity of HLTF. Interacts (deacetylated form) with EP300; the interaction enhances gene expression. Interacts with HDAC1 and JUN. Interacts with ELF1; the interaction is inhibited by glycosylation of SP1. Interaction with NFYA; the interaction is inhibited by glycosylation of SP1. Interacts with SMARCA4/BRG1 (By similarity). Interacts with ATF7IP and TBP. INTERACTION: Q92988:DLX4; NbExp=4; IntAct=EBI-298336, EBI-1752755; Q01094:E2F1; NbExp=2; IntAct=EBI-298336, EBI-448924; P32519:ELF1; NbExp=2; IntAct=EBI-298336, EBI-765526; P03372:ESR1; NbExp=2; IntAct=EBI-298336, EBI-78473; P51610:HCFC1; NbExp=4; IntAct=EBI-298336, EBI-396176; Q13118:KLF10; NbExp=2; IntAct=EBI-298336, EBI-1389509; P01106:MYC; NbExp=4; IntAct=EBI-298336, EBI-447544; P16333:NCK1; NbExp=2; IntAct=EBI-298336, EBI-389883; P23708:Nfya (xeno); NbExp=18; IntAct=EBI-298336, EBI-862337; Q8IXK0:PHC2; NbExp=2; IntAct=EBI-298336, EBI-713786; Q7Z3K3:POGZ; NbExp=2; IntAct=EBI-298336, EBI-1389308; P14859:POU2F1; NbExp=2; IntAct=EBI-298336, EBI-624770; Q15459:SF3A1; NbExp=2; IntAct=EBI-298336, EBI-1054743; Q13485:SMAD4; NbExp=2; IntAct=EBI-298336, EBI-347263; Q12772:SREBF2; NbExp=3; IntAct=EBI-298336, EBI-465059; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nuclear location is governed by glycosylated/phosphorylated states. Insulin promotes nuclear location, while glucagon favors cytoplasmic location. TISSUE SPECIFICITY: Up-regulated in adenocarcinomas of the stomach (at protein level). INDUCTION: By insulin. PTM: Phosphorylated on multiple serine and threonine residues. Phosphorylation is coupled to ubiquitination, sumoylation and proteolytic processing. Phosphorylation on Ser-59 enhances proteolytic cleavage. Phosphorylation on Ser-7 enhances ubiquitination and protein degradation. Hyperphosphorylation on Ser-101 in response to DNA damage has no effect on transcriptional activity. MAPK1/MAPK3-mediated phosphorylation on Thr-453 and Thr- 739 enhances VEGF transcription but, represses FGF2-triggered PDGFR-alpha transcription. Also implicated in the repression of RECK by ERBB2. Hyperphosphorylated on Thr-278 and Thr-739 during mitosis by MAPK8 shielding SP1 from degradation by the ubiquitin- dependent pathway. Phosphorylated in the zinc-finger domain by calmodulin-activated PKCzeta. Phosphorylation on Ser-641 by PKCzeta is critical for TSA-activated LHR gene expression through release of its repressor, p107. Phosphorylation on Thr-668, Ser- 670 and Thr-681 is stimulated by angiotensin II via the AT1 receptor inducing increased binding to the PDGF-D promoter. This phosphorylation is increased in injured artey wall. Ser-59 and Thr-681 can both be dephosphorylated by PP2A during cell-cycle interphase. Dephosphorylation on Ser-59 leads to increased chromatin association during interphase and increases the transcriptional activity. On insulin stimulation, sequentially glycosylated and phosphorylated on several C-terminal serine and threonine residues. PTM: Acetylated. Acetylation/deacetylation events affect transcriptional activity. Deacetylation leads to an increase in the expression the 12(s)-lipooxygenase gene though recruitment of p300 to the promoter. PTM: Ubiquitinated. Ubiquitination occurs on the C-terminal proteolytically-cleaved peptide and is triggered by phosphorylation. PTM: Sumoylated with SUMO1. Sumoylation modulates proteolytic cleavage of the N-terminal repressor domain. Sumoylation levels are attenuated during tumorigenesis. Phosphorylation mediates SP1 desumoylation. PTM: Proteolytic cleavage in the N-terminal repressor domain is prevented by sumoylation. The C-terminal cleaved product is susceptible to degradation. PTM: O-glycosylated; contains at least 8 N-acetylglucosamine side chains. Levels are controlled by insulin and the SP1 phosphorylation states. Insulin-mediated O-glycosylation locates SP1 to the nucleus, where it is sequentially deglycosylated and phosphorylated. O-glycosylation affects transcriptional activity through disrupting the interaction with a number of transcription factors including ELF1 and NFYA. Also inhibits interaction with the HIV1 promoter. Inhibited by peroxisomome proliferator receptor gamma (PPARgamma). MISCELLANEOUS: In the hepatoma cell line Hep-G2, SP1 precursor mRNA may undergo homotype trans-splicing leading to the duplication of exons 2 and 3. SIMILARITY: Belongs to the Sp1 C2H2-type zinc-finger protein family. SIMILARITY: Contains 3 C2H2-type zinc fingers. SEQUENCE CAUTION: Sequence=AAH43224.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P08047
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001046 core promoter sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001103 RNA polymerase II repressing transcription factor binding GO:0003676 nucleic acid binding GO:0003677 DNA binding GO:0003690 double-stranded DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0008022 protein C-terminus binding GO:0008134 transcription factor binding GO:0035035 histone acetyltransferase binding GO:0042803 protein homodimerization activity GO:0042826 histone deacetylase binding GO:0043425 bHLH transcription factor binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding GO:0046872 metal ion binding GO:0070491 repressing transcription factor binding GO:0071837 HMG box domain binding
Biological Process: GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0010628 positive regulation of gene expression GO:0016032 viral process GO:0032869 cellular response to insulin stimulus GO:0033194 response to hydroperoxide GO:0042795 snRNA transcription from RNA polymerase II promoter GO:0043536 positive regulation of blood vessel endothelial cell migration GO:0043923 positive regulation by host of viral transcription GO:0045540 regulation of cholesterol biosynthetic process GO:0045766 positive regulation of angiogenesis GO:0045893 positive regulation of transcription, DNA-templated GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048511 rhythmic process GO:0100057 regulation of phenotypic switching by transcription from RNA polymerase II promoter GO:1904828 positive regulation of hydrogen sulfide biosynthetic process GO:1905564 positive regulation of vascular endothelial cell proliferation
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
