SP1

gene
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Summary

SP1 (Sp1 transcription factor, HGNC:11205) is a protein-coding gene on chromosome 12q13.13, encoding Transcription factor Sp1 (P08047). Transcription factor that can activate or repress transcription in response to physiological and pathological stimuli. It is a selective cancer dependency (DepMap: 12.6% of cell lines).

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, glycosylation, and proteolytic processing significantly affect the activity of this protein, which can be an activator or a repressor. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6667 — RefSeq curated summary.

At a glance

  • GWAS associations: 17
  • Clinical variants (ClinVar): 72 total
  • Druggable target: yes — 1 molecules with ChEMBL bioactivity
  • Cancer dependency (DepMap): dependent in 12.6% of screened cell lines
  • Transcription factor: yes — 1,379 downstream targets (CollecTRI)
  • MANE Select transcript: NM_138473

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:11205
Approved symbolSP1
NameSp1 transcription factor
Location12q13.13
Locus typegene with protein product
StatusApproved
Ensembl geneENSG00000185591
Ensembl biotypeprotein_coding
OMIM189906
Entrez6667

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000327443, ENST00000426431, ENST00000548560, ENST00000551969, ENST00000854917

RefSeq mRNA: 3 — MANE Select: NM_138473 NM_001251825, NM_003109, NM_138473

CCDS: CCDS44898, CCDS8857

Canonical transcript exons

ENST00000327443 — 6 exons

ExonStartEnd
ENSE000012627515340936253409561
ENSE000012627555340658553406753
ENSE000013008235341092753416446
ENSE000013234245338211053383622
ENSE000023288835338017653380298
ENSE000034764925338165953381813

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 97.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2244 / max 325.6449, expressed in 1799 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter IDTPM avgSamples expressed
1257467.50201724
1257505.97681601
1257481.2233821
1257451.1884833
1257530.6000323
1257510.2935116
1257520.210361
1257470.175658
1257540.03016
1257490.02438

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
nippleUBERON:000203097.08gold quality
trabecular bone tissueUBERON:000248394.96gold quality
skin of hipUBERON:000155494.71gold quality
colonic epitheliumUBERON:000039794.00gold quality
monocyteCL:000057693.68gold quality
mammalian vulvaUBERON:000099793.56gold quality
mononuclear cellCL:000084293.28gold quality
leukocyteCL:000073893.23gold quality
upper leg skinUBERON:000426293.20gold quality
mammary ductUBERON:000176592.94gold quality
cardia of stomachUBERON:000116292.88gold quality
tonsilUBERON:000237292.50gold quality
oral cavityUBERON:000016792.45gold quality
calcaneal tendonUBERON:000370192.17gold quality
medial globus pallidusUBERON:000247792.10gold quality
pylorusUBERON:000116692.07gold quality
jejunal mucosaUBERON:000039991.85gold quality
secondary oocyteCL:000065591.81gold quality
pharyngeal mucosaUBERON:000035591.58gold quality
esophagus mucosaUBERON:000246991.54gold quality
bloodUBERON:000017891.53gold quality
rectumUBERON:000105291.46gold quality
urethraUBERON:000005791.35gold quality
vena cavaUBERON:000408791.30gold quality
gall bladderUBERON:000211091.25gold quality
renal medullaUBERON:000036291.24gold quality
tendonUBERON:000004391.10gold quality
lower esophagus mucosaUBERON:003583490.97gold quality
superior surface of tongueUBERON:000737190.85gold quality
tendon of biceps brachiiUBERON:000818890.69gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes8.64
E-GEOD-100618no440.50

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1379 targets.

TargetRegulation
A4GALTUnknown
AACS
ABCA1Activation
ABCA2Activation
ABCB1Activation
ABCB8Activation
ABCC1Repression
ABCC2
ABCC3Activation
ABCC6Activation
ABCC8Activation
ABCG1
ABCG2Unknown
ABL1
ABO
ACACAActivation
ACACBActivation
ACANUnknown
ACAT1
ACHEActivation
ACKR1Activation
ACLYRepression
ACO1Unknown
ACP5Activation
ACSBG1Unknown
ACSL4Activation
ACSS1Activation
ACSS2Activation
ACTA1Unknown
ACTA2

JASPAR motifs

MotifNameFamily
MA0079.1SP1Three-zinc finger Kruppel-related
MA0079.2SP1Three-zinc finger Kruppel-related
MA0079.3SP1Three-zinc finger Kruppel-related
MA0079.4SP1Three-zinc finger Kruppel-related
MA0079.5SP1Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:2192357, PMID:17916232, PMID:22021377

Upstream regulators (CollecTRI, top): AP1, AR, ARNT, ATM, CDX2, CEBPA, CEBPB, CEBPD, CEBPG, E2F4, E2F7, EGR1, ESR1, ESRRA, ETS1, GATA3, HDAC1, HDAC2, HIF1A, HMGA1, IFI16, IRF1, IRF6, JUN, KLF11, LEF1, MAZ, MYB, MYBL2, MYOD1, NFATC1, NFIC, NFKB1, NFKB, NKX2-1, NR3C2, NR5A1, OCLN, PARP1, PAX1

miRNA regulators (miRDB)

320 targeting SP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-190A-3P100.0080.355520
HSA-MIR-5011-5P100.0083.465820
HSA-MIR-8485100.0077.574731
HSA-MIR-3924100.0072.092394
HSA-MIR-3613-3P100.0076.367965
HSA-MIR-3163100.0077.238605
HSA-MIR-1277-5P100.0073.955056
HSA-MIR-432-3P100.0067.86705
HSA-MIR-29A-3P100.0073.111835
HSA-MIR-29B-3P100.0073.181833
HSA-MIR-29C-3P100.0073.151833
HSA-MIR-5692B100.0071.322622
HSA-MIR-5692C100.0071.322622
HSA-MIR-4747-5P100.0067.902681
HSA-MIR-5196-5P100.0067.982761
HSA-MIR-6876-5P100.0067.682126
HSA-MIR-3646100.0073.565283
HSA-MIR-5193100.0067.261744
HSA-MIR-4476100.0068.182030
HSA-MIR-4510100.0066.602050
HSA-MIR-6127100.0066.762188
HSA-MIR-6129100.0066.462080
HSA-MIR-6130100.0066.692012
HSA-MIR-6133100.0066.482064
HSA-LET-7A-3P100.0074.033932
HSA-LET-7B-3P100.0074.083913
HSA-LET-7F-1-3P100.0074.023928
HSA-MIR-98-3P100.0074.083907
HSA-MIR-4673100.0066.641490
HSA-MIR-4682100.0068.891258

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

  • role in interferon-gamma mediated suppression of macrophage lipoprotein lipase gene transcription (PMID:11796707)
  • role in identifying sterol-indendent regulatory elements in human ATP-binding cassette transporter A1 promoter (PMID:11839742)
  • hinge region of the human papillomavirus type 8 E2 protein activates the human p21(WAF1/CIP1) promoter via interaction with Sp1 (PMID:11842244)
  • role in regulating growth-promoting gene IEX-1 (PMID:11844788)
  • role in regulating 11beta-hydroxysteroid dehydrogenase type 2 promoter (PMID:11850421)
  • AP-2 down-regulates transcription of the human SOD2 gene via its interaction with Sp1 within the promoter region. (PMID:11853549)
  • The expression of the ABO promoter is influenced by the binding of transcription factor Sp1 or Sp1-like protein(s) in both erythroid and epithelial cell lineages. (PMID:11856466)
  • Role of Sp1 and Sp3 in the nutrient-regulated expression of the human asparagine synthetase gene (PMID:11867623)
  • Binding of Sp1 to the 5’ end Sp1-I site is critical for maximal activity of the Fc gamma RIIIA promoter Pmed1, which directs NK/T cell-specific expression of heterologous genes. (PMID:11884455)
  • Enhancement of binding between the c-Jun-Sp1 complex and the Sp1 oligonucleotide was observed in cells treated with PMA, suggesting the possible interaction of c-Jun-Sp1 with GC-rich binding sites in the 12(S)-lipoxygenase gene promoter. (PMID:11914583)
  • huntingtin interacts with Sp1 and TAFII130; transcriptional activity of SP1 and TAFII130 disrupted in early Huntingtin’s Disease (PMID:11988536)
  • Sp1 and the ets-related transcription factor complex GABP alpha/beta functionally cooperate to activate the utrophin promoter. (PMID:11997063)
  • recruits SV40 capsid proteins to the viral packaging signal, ses (PMID:12021324)
  • phosphorylated during late Herpes simplex virus type 1 infection and may contribute to decrease of IE and E gene expression (PMID:12050359)
  • demonstrates role of the Sp1 protein in basal and estrogen-induced growth and gene expression in breast cancer (PMID:12052832)
  • conclude that E2F proteins and Sp1 play an important role in the control of p18 expression (PMID:12077144)
  • Mutation of the progesterone receptor promoter Sp1 site eliminated the effect of hPR activation. Activity was increased by Sp1 overexpression. Dephosphorylated Sp1, abundant in decidual cells, enhances binding to DNA & hPR increasing promoter activity. (PMID:12088866)
  • The hexosamine pathway regulates the plasminogen activator inhibitor-1 gene promoter and Sp1 transcriptional activation through protein kinase C-betaI and -delta. (PMID:12105191)
  • cooperation with hepatocyte nuclear factor-4 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line (PMID:12133007)
  • RAI acts as an efficient inhibitor of HIV-1 gene expression in which both NF-kappaB and Sp1 play major roles. (PMID:12134007)
  • role in activating p21(WAF/CIP1) expression accompanying 3,3’-diindolylmethane induced G(1) cell cycle arrest in human breast cancer cells (PMID:12151347)
  • Results suggest that Sp1 and Sp3 associate with the hTERT promoter, recruiting HDAC for the localized deacetylation of nucleosomal histones and transcriptional silencing of the hTERT gene in normal human somatic cells (PMID:12151407)
  • Sp1 plays a role in regulation of promoter activity and in PKA-mediated expression of mitochondrial serine:pyruvate aminotransferase (PMID:12169688)
  • TGF-beta1 inhibition of COL2A1 gene transcription in articular chondrocytes is mediated by an increase of the Sp3/Sp1 ratio and by the repression of Sp1 transactivating effects on that gene (PMID:12186868)
  • IGFBP-3 promoter is activated by Trichostatin A-upregulated Sp1 (PMID:12200149)
  • Sp1 regulates human reduced folate carrier gene expression (PMID:12228234)
  • Sp1 regulates basal endoglin transcription in human and mammalian cells (PMID:12228247)
  • role of transcription factors Sp1 and Sp3 in the regulation of telomerase activity and human telomerase reverse transcriptase (hTERT) in Jurkat T cells (PMID:12297462)
  • there is a mechanically coupled transcriptional circuit that promotes binding of p38 to Sp1 in the nucleus (PMID:12324467)
  • findings underline an essential role of AP-2/Sp1 recognition sites in UVB-mediated VEGF expression by the keratinocyte-derived cell line HaCaT (PMID:12358602)
  • role in regulating megakaryocyte-specific glycoprotein VI promoter (PMID:12359731)
  • This protein plays a role in the identification of regulatory elements in the human adipose most abundant gene transcript-1(apM-1)promoter. (PMID:12378384)
  • Sp1 binds to specific elements of the proximal promoter and interacts with factors bound to distal enhancer elements to govern the hepatic activity of the p21 promoter under basal or inducible conditions. (PMID:12379120)
  • Binding of Sp1 to the proximal promoter links constitutive expression of the human uPA Phosphorylation of Sp1 determines the presence in vivo and the functionality of the GC-/GA-rich element of the uPA regulatory region in PC3 cells (PMID:12384434)
  • TCL1 oncogene transactivation by Sp1. (PMID:12421830)
  • confirms the synergistic transactivating role of NF-YA isoforms and Sp1 for the cystathionine beta synthase 1b promoter (PMID:12427542)
  • role in enhancing cyclin D1 promoter activity in conjunction with galectin-3 (PMID:12439750)
  • Tat and trans-activation-responsive (TAR) RNA-independent induction of HIV-1 long terminal repeat by human and murine cyclin T1 requires this protein. (PMID:12458222)
  • role for Sp1 in the regulation of expression of the angiogenic factor TP in colon cancer WiDr cells (PMID:12466967)
  • Alterations in the binding activity of Sp1 transcription factor to the sodium/iodide symporter (NIS) promoter results at least in part in reduced expression and transport of NIS in thyroid tumors. (PMID:12475396)

Cross-species orthologs

6 orthologs

OrganismSymbolGene ID
danio_reriosp1ENSDARG00000088347
ENSDARG00000113284
mus_musculusSp1ENSMUSG00000001280
rattus_norvegicusSp1ENSRNOG00000014084
drosophila_melanogasterpadFBGN0038418
drosophila_melanogasterSppsFBGN0039169

Paralogs (3): SP4 (ENSG00000105866), SP2 (ENSG00000167182), SP3 (ENSG00000172845)

Protein

Protein identifiers

Transcription factor Sp1P08047 (reviewed: P08047)

All UniProt accessions (3): P08047, H3BUU5, H3BVI2

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with ATF7IP, ATF7IP2, BAHD1, POGZ, HCFC1, AATF and PHC2. 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 ATF7IP and TBP. Interacts with MEIS2 isoform 4 and PBX1 isoform PBX1a. Interacts with EGR1. Interacts with SMARCA4/BRG1. Interacts with RNF112 in an oxidative stress-regulated manner. Interacts with ZBTB7A; ZBTB7A prevents the binding to GC-rich motifs in promoters and represses the transcriptional activity of SP1. Interacts with DDX3X; this interaction potentiates SP1-induced CDKN1A/WAF1/CIP1 transcription. Interacts with MSX1; the interaction may inhibit MSX1 autoinactivation. (Microbial infection) Interacts with varicella-zoster virus IE62 protein. (Microbial infection) 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. (Microbial infection) Interacts with HIV-1 Vpr; the interaction is inhibited by SP1 O-glycosylation.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Up-regulated in adenocarcinomas of the stomach (at protein level). Isoform 3 is ubiquitously expressed at low levels.

Post-translational modifications. 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. Acetylated. Acetylation/deacetylation events affect transcriptional activity. Deacetylation leads to an increase in the expression of the 12(s)-lipooxygenase gene through recruitment of p300 to the promoter. Deacetylated by HDAC6 which leads to increased expression of ENG and positive regulation of angiogenesis. Ubiquitinated. Ubiquitination occurs on the C-terminal proteolytically-cleaved peptide and is triggered by phosphorylation. Sumoylated with SUMO1. Sumoylation modulates proteolytic cleavage of the N-terminal repressor domain. Sumoylation levels are attenuated during tumorigenesis. Phosphorylation mediates SP1 desumoylation. Proteolytic cleavage in the N-terminal repressor domain is prevented by sumoylation. The C-terminal cleaved product is susceptible to degradation. O-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).

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Induction. By insulin.

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.

Isoforms (3)

UniProt IDNamesCanonical?
P08047-11, Sp1ayes
P08047-22, Sp1b
P08047-33, Sp1c

RefSeq proteins (3): NP_001238754, NP_003100, NP_612482* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR013087Znf_C2H2_typeDomain
IPR036236Znf_C2H2_sfHomologous_superfamily

Pfam: PF00096

UniProt features (112 total): mutagenesis site 45, modified residue 18, region of interest 10, compositionally biased region 7, glycosylation site 6, strand 4, helix 4, turn 4, zinc finger region 3, cross-link 2, splice variant 2, sequence conflict 2, initiator methionine 1, chain 1, short sequence motif 1, site 1, sequence variant 1

Structure

Experimental structures (PDB)

11 structures.

PDBMethodResolution (Å)
1SP1SOLUTION NMR
1SP2SOLUTION NMR
1VA1SOLUTION NMR
1VA2SOLUTION NMR
1VA3SOLUTION NMR
6PV0SOLUTION NMR
6PV1SOLUTION NMR
6PV2SOLUTION NMR
6PV3SOLUTION NMR
6UCOSOLUTION NMR
6UCPSOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P08047-F139.980.01

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 63–64 (cleavage)

Post-translational modifications (20): 2, 2, 7, 59, 101, 278, 453, 612, 640, 641, 651, 668, 670, 681, 698, 702, 703, 739, 16, 16

Glycosylation sites (6): 491, 612, 640, 641, 698, 702

Mutagenesis-validated functional residues (45):

PositionPhenotype
7increase in protein stability. no change in sumoylation.
15enhanced transcriptional activity.
16loss of sumoylation. no cleavage and reduced transcriptional activity.
18loss of sumoylation. increased cleavage and enhanced transcriptional activity.
19no effect on sumoylation nor on proteolytic cleavage.
36no effect on phosphorylation on dna damage.
56no effect on phosphorylation on dna damage.
59loss of phosphorylation. no effect on activated mapk8-mediated phosphorylation. similar loss of phosphorylation as by de
59some association with chromatin, increased phosphorylation levels and decreased glycosylation.
73little effect on activated mapk8-mediated phosphorylation.
81no effect on phosphorylation on dna damage.
85no effect on phosphorylation on dna damage.
98no effect on phosphorylation on dna damage.
101significant reduction of phosphorylation on dna damage.
101increase in phosphorylation on dna damage.
117no effect on activated mapk8-mediated phosphorylation.
220no effect on dephosphorylation by pp2a.
250no effect on phosphorylation on dna damage.
278almost complete abolition of activated mapk8-mediated phosphorylation and 40% reduction in protein levels during mitosis
278increased protein stability during mitosis; when associated with d-739.
281no effect on phosphorylation on dna damage.
291no effect on phosphorylation on dna damage.
296no effect on phosphorylation on dna damage.
313no effect on phosphorylation on dna damage.
351no effect on phosphorylation on dna damage.

Function

Pathways and Gene Ontology

Reactome pathways

45 pathways

IDPathway
R-HSA-1989781PPARA activates gene expression
R-HSA-2173796SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
R-HSA-2426168Activation of gene expression by SREBF (SREBP)
R-HSA-2559585Oncogene Induced Senescence
R-HSA-6807505RNA polymerase II transcribes snRNA genes
R-HSA-9018519Estrogen-dependent gene expression
R-HSA-9735871SARS-CoV-1 targets host intracellular signalling and regulatory pathways
R-HSA-9762293Regulation of CDH11 gene transcription
R-HSA-9764790Positive Regulation of CDH1 Gene Transcription
R-HSA-9818030NFE2L2 regulating tumorigenic genes
R-HSA-9839394TGFBR3 expression
R-HSA-1430728Metabolism
R-HSA-1500931Cell-Cell communication
R-HSA-162582Signal Transduction
R-HSA-1643685Disease
R-HSA-1655829Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-170834Signaling by TGF-beta Receptor Complex
R-HSA-212436Generic Transcription Pathway
R-HSA-2173793Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-2262752Cellular responses to stress
R-HSA-2559583Cellular Senescence
R-HSA-400206Regulation of lipid metabolism by PPARalpha
R-HSA-418990Adherens junctions interactions
R-HSA-421270Cell-cell junction organization
R-HSA-446728Cell junction organization
R-HSA-556833Metabolism of lipids
R-HSA-5663205Infectious disease
R-HSA-73857RNA Polymerase II Transcription
R-HSA-74160Gene expression (Transcription)
R-HSA-8939211ESR-mediated signaling

MSigDB gene sets: 501 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, MODULE_97, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, PID_TELOMERASE_PATHWAY, PID_HNF3B_PATHWAY, FISCHER_G1_S_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_AMIDE_METABOLIC_PROCESS, CMYB_01, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_TRANSCRIPTION, AAGCCAT_MIR135A_MIR135B, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, TATTATA_MIR374, MODULE_182, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM

GO Biological Process (18): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of gene expression (GO:0010628), cellular response to insulin stimulus (GO:0032869), response to hydroperoxide (GO:0033194), cellular response to zinc ion starvation (GO:0034224), positive regulation of blood vessel endothelial cell migration (GO:0043536), host-mediated activation of viral transcription (GO:0043923), positive regulation of angiogenesis (GO:0045766), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), rhythmic process (GO:0048511), cellular response to estrogen stimulus (GO:0071391), positive regulation of amyloid-beta formation (GO:1902004), cellular response to wortmannin (GO:1904568), positive regulation of hydrogen sulfide biosynthetic process (GO:1904828), positive regulation of vascular endothelial cell proliferation (GO:1905564), positive regulation of apoptotic signaling pathway (GO:2001235)

GO Molecular Function (21): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coregulator binding (GO:0001221), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), histone acetyltransferase binding (GO:0035035), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), histone deacetylase binding (GO:0042826), bHLH transcription factor binding (GO:0043425), sequence-specific DNA binding (GO:0043565), molecular adaptor activity (GO:0060090), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): chromatin (GO:0000785), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), transcription repressor complex (GO:0017053), protein-DNA complex (GO:0032993)

Reactome top-level categories

Rollup of top-16 pathways:

CategoryPathways
RNA Polymerase II Transcription2
Regulation of lipid metabolism by PPARalpha1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer1
Regulation of cholesterol biosynthesis by SREBP (SREBF)1
Cellular Senescence1
ESR-mediated signaling1
SARS-CoV-1-host interactions1
Regulation of CDH11 Expression and Function1
Regulation of CDH1 Gene Transcription1
Nuclear events mediated by NFE2L21
Signaling by TGFBR31
Metabolism of steroids1
Signaling by TGFB family members1
Signaling by TGF-beta Receptor Complex1
Generic Transcription Pathway1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
regulation of DNA-templated transcription3
RNA polymerase II transcription regulatory region sequence-specific DNA binding3
cellular anatomical structure3
DNA-templated transcription2
regulation of gene expression2
transcription by RNA polymerase II2
regulation of transcription by RNA polymerase II2
transcription cis-regulatory region binding2
chromatin2
DNA binding2
enzyme binding2
DNA-binding transcription factor binding2
binding2
regulation of RNA biosynthetic process1
gene expression1
positive regulation of macromolecule biosynthetic process1
response to insulin1
cellular response to peptide hormone stimulus1
response to oxidative stress1
response to oxygen-containing compound1
cellular response to starvation1
response to zinc ion starvation1
positive regulation of endothelial cell migration1
blood vessel endothelial cell migration1
regulation of blood vessel endothelial cell migration1
host-mediated perturbation of viral transcription1
host-mediated activation of viral process1
angiogenesis1
regulation of angiogenesis1
positive regulation of vasculature development1
positive regulation of RNA biosynthetic process1
positive regulation of DNA-templated transcription1
biological_process1
cellular response to hormone stimulus1
response to estrogen1
amyloid-beta formation1
regulation of amyloid-beta formation1
positive regulation of amyloid precursor protein catabolic process1
cellular response to ketone1
response to wortmannin1

Protein interactions and networks

STRING

3280 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
SP1ESR1P03372979
SP1EP300Q09472969
SP1TP53P04637928
SP1TBPP20226900
SP1E2F1Q01094884
SP1MYCP01106883
SP1HTTP42858849
SP1CREBBPQ92793845
SP1JUNP05412827
SP1SMAD2Q15796791
SP1EPAS1Q99814787
SP1ESR2Q92731786
SP1HDAC1Q13547780
SP1SMAD3P84022774
SP1HIF1AQ16665771

IntAct

213 interactions, top by confidence:

ABTypeScore
STAT3psi-mi:“MI:0914”(association)0.730
POU2F1SP1psi-mi:“MI:0915”(physical association)0.720
SP1POU2F1psi-mi:“MI:0915”(physical association)0.720
POU2F1SP1psi-mi:“MI:0407”(direct interaction)0.720
SP1POU2F1psi-mi:“MI:0407”(direct interaction)0.720
SP1HCFC1psi-mi:“MI:0915”(physical association)0.680
SP1STAT3psi-mi:“MI:0915”(physical association)0.650
SP1STAT3psi-mi:“MI:2364”(proximity)0.650
SREBF2SP1psi-mi:“MI:0915”(physical association)0.630
SP1SREBF2psi-mi:“MI:0915”(physical association)0.630
SP1psi-mi:“MI:0407”(direct interaction)0.600
SP1psi-mi:“MI:0914”(association)0.600
SP1DLX4psi-mi:“MI:0915”(physical association)0.600
DLX4SP1psi-mi:“MI:0407”(direct interaction)0.600
FHL2SP1psi-mi:“MI:0407”(direct interaction)0.590
TP53SP1psi-mi:“MI:0915”(physical association)0.590
SP1TP53psi-mi:“MI:0915”(physical association)0.590
SP1vp3psi-mi:“MI:0915”(physical association)0.590

BioGRID (782): SP3 (Reconstituted Complex), SP1 (Reconstituted Complex), SP1 (Affinity Capture-Western), JUN (Affinity Capture-Western), HIC1 (Co-localization), PIN1 (Affinity Capture-Western), SP1 (Affinity Capture-Western), CDK1 (Affinity Capture-Western), CCNB1 (Affinity Capture-Western), SP1 (Biochemical Activity), SP1 (Biochemical Activity), SP1 (Affinity Capture-RNA), PPARG (Affinity Capture-Western), SP1 (Affinity Capture-Western), SP1 (Affinity Capture-Western)

ESM2 similar proteins: A0JME2, A5D7F6, F8VPZ9, O88873, O89090, P08047, P31367, P52591, P54253, P58929, P70178, P78364, Q01714, Q02086, Q07916, Q08E26, Q13227, Q14863, Q2VPU4, Q3U182, Q5E9U0, Q64028, Q66JY2, Q6AI39, Q6T264, Q7Z3K3, Q8BLM0, Q8BZH4, Q8CHH5, Q8CHP6, Q8IXK0, Q8IZL2, Q8K3Z9, Q8K4J6, Q8N196, Q8N1G0, Q8NDX5, Q8QHL5, Q8VHG2, Q91VX2

Diamond homologs: A5ABV9, O08876, O14901, O70494, O89090, O89091, P08047, P0CG40, P41696, Q01714, Q02446, Q02447, Q0VA40, Q13351, Q22678, Q3SY56, Q5XGT8, Q62445, Q64HY3, Q64HY5, Q6BEB4, Q6NW96, Q6P0J3, Q8BMJ8, Q8IXZ3, Q8K1S5, Q8TDD2, Q8VI67, Q90WR8, Q9ESX2, Q9JHX2, Q9TZ64, A1C6L9, A1DH89, A2QCJ9, B0XSK6, B8NGC8, G4N3L5, K9GKQ6, O14335

SIGNOR signaling

104 interactions.

AEffectBMechanism
MAPK1up-regulatesSP1phosphorylation
MAPK3up-regulatesSP1phosphorylation
PRKCZup-regulatesSP1phosphorylation
CDK1up-regulatesSP1phosphorylation
ATMunknownSP1phosphorylation
MAPK8up-regulatesSP1phosphorylation
SP1“form complex”SP1/STAT3binding
NfKb-p65/p50up-regulatesSP1binding
CyclinB/CDK1up-regulatesSP1phosphorylation
SP1“up-regulates activity”CRXbinding
SP1“up-regulates quantity by expression”RHO“transcriptional regulation”
TFAP4“up-regulates activity”SP1binding
ERK1/2“up-regulates activity”SP1phosphorylation
PPP2CA“up-regulates activity”SP1dephosphorylation
MAPK3“up-regulates activity”SP1phosphorylation
CSNK2A1“down-regulates activity”SP1phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

PathwayPartnersFoldFDR
Downstream signal transduction522.1×4e-04
Transcriptional regulation by RUNX3515.8×1e-03
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)915.3×5e-06
FCGR3A-mediated phagocytosis715.2×1e-04
Cyclin D associated events in G1513.6×2e-03
Regulation of PTEN gene transcription612.4×1e-03
Transcriptional regulation by RUNX1711.9×4e-04
Regulation of actin dynamics for phagocytic cup formation510.7×4e-03

GO biological processes:

GO termPartnersFoldFDR
positive regulation of miRNA transcription1234.5×3e-13
embryonic digit morphogenesis617.9×1e-04
ephrin receptor signaling pathway517.0×1e-03
cellular response to hydrogen peroxide716.2×4e-05
cellular response to transforming growth factor beta stimulus513.7×3e-03
DNA-templated transcription511.1×5e-03
BMP signaling pathway59.9×7e-03
response to hypoxia87.6×1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

72 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance61
Likely benign4
Benign2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1012 predictions. Top by Δscore:

VariantEffectΔscore
12:53380296:GCG:Gdonor_gain1.0000
12:53381809:GGCAG:Gdonor_gain1.0000
12:53381810:GCAG:Gdonor_gain1.0000
12:53381810:GCAGG:Gdonor_gain1.0000
12:53381811:CAGGT:Cdonor_loss1.0000
12:53381814:G:Cdonor_loss1.0000
12:53381815:T:Adonor_loss1.0000
12:53382103:C:Aacceptor_gain1.0000
12:53406577:A:AGacceptor_gain1.0000
12:53406581:TCA:Tacceptor_loss1.0000
12:53406583:A:AGacceptor_gain1.0000
12:53406583:A:Tacceptor_loss1.0000
12:53406583:AG:Aacceptor_gain1.0000
12:53406583:AGGT:Aacceptor_gain1.0000
12:53406584:G:Aacceptor_gain1.0000
12:53406584:G:GGacceptor_gain1.0000
12:53406584:GGT:Gacceptor_gain1.0000
12:53406584:GGTG:Gacceptor_gain1.0000
12:53406584:GGTGA:Gacceptor_gain1.0000
12:53406749:GGAAG:Gdonor_gain1.0000
12:53406750:GAAG:Gdonor_gain1.0000
12:53406750:GAAGG:Gdonor_gain1.0000
12:53406751:A:Tdonor_gain1.0000
12:53406751:AAG:Adonor_gain1.0000
12:53406752:AG:Adonor_gain1.0000
12:53406752:AGGTG:Adonor_loss1.0000
12:53406753:GG:Gdonor_gain1.0000
12:53406754:G:GGdonor_gain1.0000
12:53406754:GTG:Gdonor_loss1.0000
12:53409359:CAG:Cacceptor_loss1.0000

AlphaMissense

5113 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
12:53409399:T:AC628S1.000
12:53409399:T:CC628R1.000
12:53409400:G:AC628Y1.000
12:53409400:G:CC628S1.000
12:53409401:C:GC628W1.000
12:53409414:T:AC633S1.000
12:53409414:T:CC633R1.000
12:53409415:G:CC633S1.000
12:53409445:T:CL643P1.000
12:53409453:C:AH646N1.000
12:53409453:C:GH646D1.000
12:53409455:C:AH646Q1.000
12:53409455:C:GH646Q1.000
12:53409459:C:AR648S1.000
12:53409489:T:CC658R1.000
12:53409491:T:GC658W1.000
12:53409516:T:CF667L1.000
12:53409517:T:CF667S1.000
12:53409518:C:AF667L1.000
12:53409518:C:GF667L1.000
12:53409522:C:AR669S1.000
12:53409528:G:CD671H1.000
12:53409529:A:TD671V1.000
12:53409535:T:CL673P1.000
12:53409541:G:TR675M1.000
12:53409542:G:CR675S1.000
12:53409542:G:TR675S1.000
12:53409543:C:AH676N1.000
12:53409543:C:GH676D1.000
12:53409544:A:CH676P1.000

dbSNP variants (sampled 300 via entrez): RS1000039371 (12:53413338 TC>T), RS1000079005 (12:53401949 G>A), RS1000109403 (12:53414741 G>A,T), RS1000111602 (12:53406608 C>T), RS1000141427 (12:53406983 C>G), RS1000250117 (12:53380153 T>A,C,G), RS1000333264 (12:53383681 T>A,G), RS1000363742 (12:53385998 C>G), RS1000464569 (12:53396395 C>T), RS1000548584 (12:53400518 G>A), RS1000646469 (12:53405894 A>G), RS1000690960 (12:53384702 A>C), RS1000861459 (12:53388941 C>T), RS1000907420 (12:53388635 A>G), RS1001066202 (12:53394836 A>G)

Disease associations

OMIM: gene MIM:189906 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

17 associations (top):

StudyTraitp-value
GCST002942_9Percentage gas trapping6.000000e-07
GCST004601_163Red blood cell count1.000000e-10
GCST004622_118Reticulocyte count2.000000e-10
GCST004633_25Neutrophil percentage of white cells3.000000e-10
GCST005993_56Mean corpuscular hemoglobin3.000000e-15
GCST006011_86Mean corpuscular volume3.000000e-15
GCST006153_2Parkinsonism in frontotemporal lobe dementia8.000000e-06
GCST006418_11Progressive supranuclear palsy4.000000e-07
GCST006418_2Progressive supranuclear palsy4.000000e-07
GCST009672_1Hypospadias (moderate to severe)4.000000e-09
GCST010243_150Apolipoprotein B levels1.000000e-08
GCST90002385_228High light scatter reticulocyte count1.000000e-10
GCST90002392_384Mean corpuscular volume2.000000e-30
GCST90002397_202Mean spheric corpuscular volume1.000000e-40
GCST90002403_450Red blood cell count1.000000e-34
GCST90002405_304Reticulocyte count3.000000e-18
GCST90002406_336Reticulocyte fraction of red cells1.000000e-10

EFO canonical traits (6, from GWAS)

EFO IDTrait name
EFO:0007628gas trapping measurement
EFO:0004305erythrocyte count
EFO:0007986reticulocyte count
EFO:0007990neutrophil percentage of leukocytes
EFO:0004527mean corpuscular hemoglobin
EFO:0004615apolipoprotein B measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6103 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 366 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL2105734SEPANTRONIUM BROMIDE2366

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

VariantTypeLevelDrugsPhenotypes
rs2683511Efficacy,Metabolism/PK3metforminDiabetes Mellitus
rs784888Efficacy,Metabolism/PK3metforminDiabetes Mellitus;Type 2

PharmGKB variants

2 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs784888AMHR2, SP132.501metformin
rs2683511SP133.501metformin

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
8.10IC508nMSEPANTRONIUM BROMIDE

PubChem BioAssay actives

1 with measured affinity, of 23 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
1-(2-methoxyethyl)-2-methyl-3-(pyrazin-2-ylmethyl)benzo[f]benzimidazol-3-ium-4,9-dione bromide2025419: Inhibition of human SP1 transfected in PC-3 cells by renilla luciferase reporter gene assayic500.0080uM

CTD chemical–gene interactions

194 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Arsenic Trioxideaffects methylation, decreases reaction, increases reaction, affects binding, increases expression (+3 more)9
Quercetinaffects cotreatment, increases activity, affects reaction, increases expression, decreases expression (+3 more)8
mithramycin Adecreases expression, decreases reaction, increases activity, affects binding, increases reaction (+1 more)7
trichostatin Adecreases reaction, increases activity, affects binding, affects cotreatment, increases reaction (+3 more)6
Resveratroldecreases acetylation, affects binding, increases reaction, decreases activity, affects localization (+5 more)6
Doxorubicinincreases phosphorylation, affects activity, affects binding, increases reaction, decreases expression (+3 more)6
Tretinoinincreases expression, increases reaction, affects binding, increases activity6
Decitabineaffects binding, affects cotreatment, increases reaction, increases expression5
Cadmiumdecreases reaction, increases reaction, decreases activity, affects reaction, decreases expression (+2 more)5
Hydrogen Peroxideincreases reaction, decreases expression, decreases reaction, affects expression, affects binding (+3 more)5
Copper Sulfatedecreases reaction, increases expression, affects binding, decreases activity, decreases expression5
sodium arseniteaffects binding, increases abundance, increases expression, affects reaction, decreases expression (+1 more)4
Acetylcysteinedecreases expression, decreases reaction, increases expression4
Copperdecreases abundance, increases expression, increases reaction, decreases reaction, affects abundance (+1 more)4
Estradiolaffects cotreatment, increases expression, affects binding, increases reaction, decreases expression (+2 more)4
Plicamycinaffects binding, decreases reaction, increases expression, decreases activity4
nickel chlorideaffects binding, affects cotreatment, increases reaction, increases expression, decreases reaction (+2 more)3
cordycepinaffects metabolic processing, affects binding, decreases reaction, decreases expression, increases activity3
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazoleaffects cotreatment, decreases expression, affects binding, decreases reaction, increases reaction (+1 more)3
U 0126decreases expression, increases reaction, decreases reaction, increases expression, increases activity3
Camptothecinincreases expression, affects localization, increases activity, affects reaction, decreases reaction3
Metformindecreases reaction, increases expression, decreases expression, affects binding, affects cotreatment (+1 more)3
Tetrachlorodibenzodioxinaffects binding, increases reaction, increases expression, decreases reaction, increases phosphorylation3
Tetradecanoylphorbol Acetateaffects localization, affects binding, increases reaction, increases expression, increases activity (+1 more)3
Valproic Acidaffects binding, increases reaction, decreases expression3
bisphenol Aincreases expression, affects cotreatment2
deoxynivalenolaffects expression, affects binding, increases reaction, increases phosphorylation, increases expression2
indole-3-carbinolaffects binding, decreases reaction, decreases activity2
tetrathiomolybdateaffects binding, increases reaction, decreases abundance, increases expression, increases activity2
benzyloxycarbonylleucyl-leucyl-leucine aldehydedecreases expression, decreases reaction2

ChEMBL screening assays

10 unique, capped per target: 8 binding, 2 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1058704BindingInhibition of SP1-dependent luciferase expressionScuteflorins A and B, dihydropyranocoumarins from Scutellaria lateriflora. — J Nat Prod
CHEMBL3061786ADMETInhibition of Sp1 (unknown origin) by luciferase reporter gene assaySynthesis and biological activity of hydrazidehydrazones and their corresponding 3-acetyl-2,5-disubstituted-2,3-dihydro-1,3,4-oxadiazoles — Med Chem Res

Cellosaurus cell lines

9 cell lines: 8 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B2H3Abcam HeLa SP1 KOCancer cell lineFemale
CVCL_B8Q1Abcam HCT 116 SP1 KOCancer cell lineMale
CVCL_B9BSAbcam MCF-7 SP1 KOCancer cell lineFemale
CVCL_B9SHAbcam A-549 SP1 KOCancer cell lineMale
CVCL_D8BBUbigene A-549 SP1 KOCancer cell lineMale
CVCL_D8W2Ubigene HCT 116 SP1 KOCancer cell lineMale
CVCL_D9STUbigene HEK293 SP1 KOTransformed cell lineFemale
CVCL_E0PSUbigene HeLa SP1 KOCancer cell lineFemale
CVCL_TQ04HAP1 SP1 (-)Cancer cell lineMale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.