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). Also binds the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. 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 BMAL1. Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity).

Classification

Family (Pfam)

PF00096 zf-C2H2

InterPro

Znf_C2H2_sf, Znf_C2H2_type

Functional cluster

RNA-Polymerase II Transcription Factors

Experimental structures · PDB · 11

• 1SP1 NMR
• 1SP2 NMR
• 1VA1 NMR
• 1VA2 NMR
• 1VA3 NMR
• 6PV0 NMR
• 6PV1 NMR
• 6PV2 NMR
• 6PV3 NMR
• 6UCO NMR
• 6UCP NMR

A predicted model is available from AlphaFold.

Gene Ontology · 45

• GO:0000785 chromatin
• GO:0005737 cytoplasm
• GO:0000791 euchromatin
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:0032993 protein-DNA complex
• GO:0017053 transcription repressor complex
• GO:0043425 bHLH transcription factor binding
• GO:0003677 DNA binding
• GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
• GO:0003700 DNA-binding transcription factor activity
• GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
• GO:0003690 double-stranded DNA binding
• GO:0035035 histone acetyltransferase binding
• GO:0042826 histone deacetylase binding
• GO:0042802 identical protein binding
• GO:0060090 molecular adaptor activity
• GO:0042803 protein homodimerization activity
• GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
• GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding
• GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
• GO:0043565 sequence-specific DNA binding
• GO:1990837 sequence-specific double-stranded DNA binding
• GO:0000976 transcription cis-regulatory region binding
• GO:0001221 transcription coregulator binding
• GO:0008270 zinc ion binding
• GO:0071391 cellular response to estrogen stimulus
• GO:0032869 cellular response to insulin stimulus
• GO:1904568 cellular response to wortmannin
• GO:0034224 cellular response to zinc ion starvation
• GO:0006351 DNA-templated transcription
• GO:0043923 host-mediated activation of viral transcription
• GO:1902004 positive regulation of amyloid-beta formation
• GO:0045766 positive regulation of angiogenesis
• GO:2001235 positive regulation of apoptotic signaling pathway
• GO:0043536 positive regulation of blood vessel endothelial cell migration
• GO:0045893 positive regulation of DNA-templated transcription
• GO:0010628 positive regulation of gene expression
• GO:1904828 positive regulation of hydrogen sulfide biosynthetic process
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:1905564 positive regulation of vascular endothelial cell proliferation
• GO:0006355 regulation of DNA-templated transcription
• GO:0006357 regulation of transcription by RNA polymerase II
• GO:0033194 response to hydroperoxide
• GO:0048511 rhythmic process

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Transcription factor Sp1 1.00
• Transcription factor Sp1 1.00
• Transcription factor Sp4 0.94
• Transcription factor Sp4 0.94
• Transcription factor Sp3 0.91
• Transcription factor Sp3 0.91
• Transcription factor Sp3 0.90
• Transcription factor Sp2 0.86
• Transcription factor Sp2 0.85
• Transcription factor Sp2 0.84
• Polyhomeotic-proximal chromatin protein 0.84
• Nuclear transcription factor Y subunit alpha 0.84

Co-cited proteins · studied together in the literature

• Protein AATF 1 shared papers
• Mitochondrial potassium channel ATP-binding subunit 1 shared papers
• Major capsid protein VP1 1 shared papers
• Minor capsid protein VP2 1 shared papers
• Nuclear transcription factor Y subunit alpha 1 shared papers
• Early growth response protein 1 1 shared papers
• Myc-associated zinc finger protein 1 shared papers
• 5-hydroxytryptamine receptor 1A 1 shared papers
• Major viral transcription factor ICP4 homolog 1 shared papers
• Zinc finger and BTB domain-containing protein 7A 1 shared papers
• Transcription factor Sp3 3 shared papers
• Activating transcription factor 7-interacting protein 2 1 shared papers

Literature · 55 cited papers

• HDAC6 Enhances Endoglin Expression through Deacetylation of Transcription Factor SP1, Potentiating BMP9-Induced Angiogenesis. Cells · 2024
• The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs. Cell. Mol. Life Sci. · 2020
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Identification of a novel Sp1 splice variant as a strong transcriptional activator. Biochem. Biophys. Res. Commun. · 2011
• Cooperative transcriptional activation by Klf4, Meis2, and Pbx1. Mol. Cell. Biol. · 2011
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Mithramycin A suppresses expression of the human melanoma-associated gene ABCB8. Mol. Genet. Genomics · 2011
• Transforming growth factor-beta-inducible early response gene 1 is a novel substrate for atypical protein kinase Cs. Cell. Mol. Life Sci. · 2011
• Snail associates with EGR-1 and SP-1 to upregulate transcriptional activation of p15INK4b. FEBS J. · 2010
• … and 43 more in the literature graph