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MGP002957

UniProt Annotations

Entry Information
Gene NameSp1 transcription factor
Protein EntrySP1_HUMAN
UniProt IDP08047
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; Synonyms=Sp1a; IsoId=P08047-1; Sequence=Displayed; Name=2; Synonyms=Sp1b; IsoId=P08047-2; Sequence=VSP_053934; Name=3; Synonyms=Sp1c; IsoId=P08047-3; Sequence=VSP_053935;
FunctionTranscription 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. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component ARNTL/BMAL1. {ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:11371615, ECO:0000269|PubMed:11904305, ECO:0000269|PubMed:14593115, ECO:0000269|PubMed:16377629, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:16943418, ECO:0000269|PubMed:17049555, ECO:0000269|PubMed:18171990, ECO:0000269|PubMed:18199680, ECO:0000269|PubMed:18239466, ECO:0000269|PubMed:18513490, ECO:0000269|PubMed:18619531, ECO:0000269|PubMed:19193796, ECO:0000269|PubMed:20091743, ECO:0000269|PubMed:21798247}.
InductionBy insulin. {ECO:0000269|PubMed:16332679}.
InteractionQ92988: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; Q99814:EPAS1; NbExp=2; IntAct=EBI-298336, EBI-447470; P03372:ESR1; NbExp=2; IntAct=EBI-298336, EBI-78473; P51610:HCFC1; NbExp=4; IntAct=EBI-298336, EBI-396176; Q16665:HIF1A; NbExp=3; IntAct=EBI-298336, EBI-447269; 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=7; IntAct=EBI-298336, EBI-624770; Q06455:RUNX1T1; NbExp=2; IntAct=EBI-298336, EBI-743342; 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;
MiscellaneousIn the hepatoma cell line Hep-G2, SP1 precursor mRNA may undergo homotype trans-splicing leading to the duplication of exons 2 and 3.
PtmAcetylated. 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. {ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692}.
PtmO-glycosylated; Contains 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).
PtmPhosphorylated 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. {ECO:0000269|PubMed:11904305, ECO:0000269|PubMed:14593115, ECO:0000269|PubMed:16332679, ECO:0000269|PubMed:16377629, ECO:0000269|PubMed:16943418, ECO:0000269|PubMed:16964243, ECO:0000269|PubMed:17049555, ECO:0000269|PubMed:18171990, ECO:0000269|PubMed:18199680, ECO:0000269|PubMed:18239466, ECO:0000269|PubMed:18258854, ECO:0000269|PubMed:18619531, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692}.
PtmProteolytic cleavage in the N-terminal repressor domain is prevented by sumoylation. The C-terminal cleaved product is susceptible to degradation.
PtmSumoylated with SUMO1. Sumoylation modulates proteolytic cleavage of the N-terminal repressor domain. Sumoylation levels are attenuated during tumorigenesis. Phosphorylation mediates SP1 desumoylation.
PtmUbiquitinated. Ubiquitination occurs on the C-terminal proteolytically-cleaved peptide and is triggered by phosphorylation. {ECO:0000269|PubMed:18239466}.
Sequence CautionSequence=AAH43224.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the Sp1 C2H2-type zinc-finger protein family. {ECO:0000305}.
SimilarityContains 3 C2H2-type zinc fingers. {ECO:0000255|PROSITE-ProRule:PRU00042}.
Subcellular LocationNucleus. Cytoplasm. Note=Nuclear location is governed by glycosylated/phosphorylated states. Insulin promotes nuclear location, while glucagon favors cytoplasmic location.
SubunitInteracts 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. Interacts with MEIS2 isoform 4 and PBX1 isoform PBX1a. Interacts with EGR1. {ECO:0000250, ECO:0000269|PubMed:10391891, ECO:0000269|PubMed:10976766, ECO:0000269|PubMed:12021324, ECO:0000269|PubMed:12847090, ECO:0000269|PubMed:12855699, ECO:0000269|PubMed:15691849, ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:19106100, ECO:0000269|PubMed:19285002, ECO:0000269|PubMed:19302979, ECO:0000269|PubMed:19666599, ECO:0000269|PubMed:20121949, ECO:0000269|PubMed:21746878, ECO:0000269|PubMed:7592727, ECO:0000269|PubMed:9466902}.
Tissue SpecificityUp-regulated in adenocarcinomas of the stomach (at protein level). Isoform 3 is ubiquitously expressed at low levels. {ECO:0000269|PubMed:21798247}.
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