Transcription factor Sp1

Transcription factor Sp1, also known as specificity protein 1* is a protein that in humans is encoded by the SP1 gene.^[5]

SP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1SP1, 1SP2, 1VA1, 1VA2, 1VA3
Identifiers
Aliases	SP1, entrez:6667, Sp1 transcription factor
External IDs	OMIM: 189906; MGI: 98372; HomoloGene: 8276; GeneCards: SP1; OMA:SP1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.13 Start 53,380,176 bp[1] End 53,416,446 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 F3 Start 102,314,578 bp[2] End 102,344,839 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in nipple trabecular bone skin of hip epithelium of colon monocyte vulva skin of thigh lactiferous duct cardia tonsil Top expressed in Rostral migratory stream vas deferens human fetus conjunctival fornix internal carotid artery hair follicle ciliary body skin of external ear lacrimal gland external carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity HMG box domain binding transcription factor binding histone deacetylase binding metal ion binding transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding bHLH transcription factor binding protein C-terminus binding protein binding histone acetyltransferase binding nucleic acid binding sequence-specific DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA binding double-stranded DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription factor activity RNA polymerase II cis-regulatory region sequence-specific DNA binding core promoter sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific cis-regulatory region sequence-specific DNA binding Cellular component cytoplasm nucleoplasm protein-DNA complex nucleus transcription repressor complex Biological process positive regulation of hydrogen sulfide biosynthetic process rhythmic process regulation of transcription by RNA polymerase II positive regulation of transcription, DNA-templated viral process regulation of transcription, DNA-templated transcription, DNA-templated snRNA transcription by RNA polymerase II cellular response to insulin stimulus positive regulation of transcription by RNA polymerase II regulation of cholesterol biosynthetic process positive regulation of gene expression positive regulation of blood vessel endothelial cell migration positive regulation of angiogenesis positive regulation of vascular endothelial cell proliferation response to hydroperoxide Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6667 20683 Ensembl ENSG00000185591 ENSMUSG00000001280 UniProt P08047 O89090 RefSeq (mRNA) NM_001251825 NM_003109 NM_138473 NM_013672 RefSeq (protein) NP_001238754 NP_003100 NP_612482 NP_038700 Location (UCSC) Chr 12: 53.38 – 53.42 Mb Chr 15: 102.31 – 102.34 Mb PubMed search [3] [4]
Wikidata
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Function

The protein encoded by this gene is a zinc finger transcription factor that binds to GC-rich motifs of many promoters. The encoded protein is involved in many cellular processes, including cell differentiation, cell growth, apoptosis, immune responses, response to DNA damage, and chromatin remodeling. post-translational modifications such as phosphorylation, acetylation, O-GlcNAcylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor.^[5]

In the SV40 virus, Sp1 binds to the GC boxes in the regulatory sequence of the genome.

Structure

SP1 belongs to the Sp/KLF family of transcription factors. The protein is 785 amino acids long, with a molecular weight of 81 kDa. The SP1 transcription factor contains two glutamine-rich activation domains at its N-terminus that are believed to be necessary for promoter trans-activation.^[6] SP1 most notably contains three zinc finger protein motifs at its C-terminus, by which it binds directly to DNA and allows for interaction of the protein with other transcriptional regulators. Its zinc fingers are of the Cys₂/His₂ type and bind the consensus sequence 5'-(G/T)GGGCGG(G/A)(G/A)(C/T)-3' (GC box element). Some 12,000 SP-1 binding sites are found in the human genome.^[7]

Applications

Sp1 has been used as a control protein to compare with when studying the increase or decrease of the aryl hydrocarbon receptor and/or the estrogen receptor, since it binds to both and generally remains at a relatively constant level.^[8]

Recently, a putative promoter region in FTMT, and positive regulators {SP1, cAMP response element-binding protein (CREB), and Ying Yang 1 (YY1)] and negative regulators [GATA2, forkhead box protein A1 (FoxA1), and CCAAT enhancer-binding protein b (C/EBPb)] of FTMT transcription have been identified (Guaraldo et al, 2016).The effect of DFP on the DNA-binding activity of these regulators to the FTMT promoter was examined using chromatin immunoprecipitation (ChIP) assay. Among the regulators, only SP1 displayed significantly increased DNA- binding activity following DFP treatment in a dose-dependent manner. SP1 knockdown by siRNA abolished the DFP-induced increase in the mRNA levels of FTMT, indicating SP1-mediated regulation of FTMT expression in the presence of DFP. Treatment with Deferiprone increased the expression of cytoplasmic and nuclear SP1 with predominant localization in the nucleus.^[9]

Inhibitors

Plicamycin, an antineoplastic antibiotic produced by Streptomyces plicatus, and Withaferin A, a steroidal lactone from Withania somnifera plant are known to inhibit Sp1 transcription factor.^[10][11]

miR-375-5p microRNA significantly decreased expression of SP1 and YAP1 in colorectal cancer cells. SP1 and YAP1 mRNAs are direct targets of miR-375-5p.^[12]

Interactions

Transcription factor Sp1 has been shown to interact with:

• AATF,^[13]
• CEBPB,^[14][15]
• COL1A1,^[16]
• E2F1,^[17][18][19]
• FOSL1,^[20]
• GABPA,^[21]
• HDAC1,^{[13][22][23][24]}
• HDAC2,^[23][24][25]
• HMGA1,^[15]
• HCFC1,^[26][27]
• HTT,^[28]
• KLF6,^[29]
• MEF2C,^[30]
• MEF2D,^[31]
• MSX1,^[32]
• Myogenin,^[33]
• POU2F1,^[26][34]
• PPP1R13L,^[35]
• PSMC5,^[36][37]
• PML,^[38]
• RELA,^[39][40]
• SMAD3,^[41][42]
• SUMO1,^[36]
• SF1,^[43]
• TAL1,^[44]
• UBC.^[36]
• WRN,^[45]
• DDX3X