SP1
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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
| Field | Value |
|---|---|
| HGNC ID | HGNC:11205 |
| Approved symbol | SP1 |
| Name | Sp1 transcription factor |
| Location | 12q13.13 |
| Locus type | gene with protein product |
| Status | Approved |
| Ensembl gene | ENSG00000185591 |
| Ensembl biotype | protein_coding |
| OMIM | 189906 |
| Entrez | 6667 |
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
| Exon | Start | End |
|---|---|---|
| ENSE00001262751 | 53409362 | 53409561 |
| ENSE00001262755 | 53406585 | 53406753 |
| ENSE00001300823 | 53410927 | 53416446 |
| ENSE00001323424 | 53382110 | 53383622 |
| ENSE00002328883 | 53380176 | 53380298 |
| ENSE00003476492 | 53381659 | 53381813 |
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 ID | TPM avg | Samples expressed |
|---|---|---|
| 125746 | 7.5020 | 1724 |
| 125750 | 5.9768 | 1601 |
| 125748 | 1.2233 | 821 |
| 125745 | 1.1884 | 833 |
| 125753 | 0.6000 | 323 |
| 125751 | 0.2935 | 116 |
| 125752 | 0.2103 | 61 |
| 125747 | 0.1756 | 58 |
| 125754 | 0.0301 | 6 |
| 125749 | 0.0243 | 8 |
Top tissues by expression
288 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| nipple | UBERON:0002030 | 97.08 | gold quality |
| trabecular bone tissue | UBERON:0002483 | 94.96 | gold quality |
| skin of hip | UBERON:0001554 | 94.71 | gold quality |
| colonic epithelium | UBERON:0000397 | 94.00 | gold quality |
| monocyte | CL:0000576 | 93.68 | gold quality |
| mammalian vulva | UBERON:0000997 | 93.56 | gold quality |
| mononuclear cell | CL:0000842 | 93.28 | gold quality |
| leukocyte | CL:0000738 | 93.23 | gold quality |
| upper leg skin | UBERON:0004262 | 93.20 | gold quality |
| mammary duct | UBERON:0001765 | 92.94 | gold quality |
| cardia of stomach | UBERON:0001162 | 92.88 | gold quality |
| tonsil | UBERON:0002372 | 92.50 | gold quality |
| oral cavity | UBERON:0000167 | 92.45 | gold quality |
| calcaneal tendon | UBERON:0003701 | 92.17 | gold quality |
| medial globus pallidus | UBERON:0002477 | 92.10 | gold quality |
| pylorus | UBERON:0001166 | 92.07 | gold quality |
| jejunal mucosa | UBERON:0000399 | 91.85 | gold quality |
| secondary oocyte | CL:0000655 | 91.81 | gold quality |
| pharyngeal mucosa | UBERON:0000355 | 91.58 | gold quality |
| esophagus mucosa | UBERON:0002469 | 91.54 | gold quality |
| blood | UBERON:0000178 | 91.53 | gold quality |
| rectum | UBERON:0001052 | 91.46 | gold quality |
| urethra | UBERON:0000057 | 91.35 | gold quality |
| vena cava | UBERON:0004087 | 91.30 | gold quality |
| gall bladder | UBERON:0002110 | 91.25 | gold quality |
| renal medulla | UBERON:0000362 | 91.24 | gold quality |
| tendon | UBERON:0000043 | 91.10 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 90.97 | gold quality |
| superior surface of tongue | UBERON:0007371 | 90.85 | gold quality |
| tendon of biceps brachii | UBERON:0008188 | 90.69 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 8.64 |
| E-GEOD-100618 | no | 440.50 |
Regulation
Is transcription factor: yes
Downstream targets (CollecTRI)
1379 targets.
| Target | Regulation |
|---|---|
| A4GALT | Unknown |
| AACS | |
| ABCA1 | Activation |
| ABCA2 | Activation |
| ABCB1 | Activation |
| ABCB8 | Activation |
| ABCC1 | Repression |
| ABCC2 | |
| ABCC3 | Activation |
| ABCC6 | Activation |
| ABCC8 | Activation |
| ABCG1 | |
| ABCG2 | Unknown |
| ABL1 | |
| ABO | |
| ACACA | Activation |
| ACACB | Activation |
| ACAN | Unknown |
| ACAT1 | |
| ACHE | Activation |
| ACKR1 | Activation |
| ACLY | Repression |
| ACO1 | Unknown |
| ACP5 | Activation |
| ACSBG1 | Unknown |
| ACSL4 | Activation |
| ACSS1 | Activation |
| ACSS2 | Activation |
| ACTA1 | Unknown |
| ACTA2 |
JASPAR motifs
| Motif | Name | Family |
|---|---|---|
| MA0079.1 | SP1 | Three-zinc finger Kruppel-related |
| MA0079.2 | SP1 | Three-zinc finger Kruppel-related |
| MA0079.3 | SP1 | Three-zinc finger Kruppel-related |
| MA0079.4 | SP1 | Three-zinc finger Kruppel-related |
| MA0079.5 | SP1 | Three-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):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-190A-3P | 100.00 | 80.35 | 5520 |
| HSA-MIR-5011-5P | 100.00 | 83.46 | 5820 |
| HSA-MIR-8485 | 100.00 | 77.57 | 4731 |
| HSA-MIR-3924 | 100.00 | 72.09 | 2394 |
| HSA-MIR-3613-3P | 100.00 | 76.36 | 7965 |
| HSA-MIR-3163 | 100.00 | 77.23 | 8605 |
| HSA-MIR-1277-5P | 100.00 | 73.95 | 5056 |
| HSA-MIR-432-3P | 100.00 | 67.86 | 705 |
| HSA-MIR-29A-3P | 100.00 | 73.11 | 1835 |
| HSA-MIR-29B-3P | 100.00 | 73.18 | 1833 |
| HSA-MIR-29C-3P | 100.00 | 73.15 | 1833 |
| HSA-MIR-5692B | 100.00 | 71.32 | 2622 |
| HSA-MIR-5692C | 100.00 | 71.32 | 2622 |
| HSA-MIR-4747-5P | 100.00 | 67.90 | 2681 |
| HSA-MIR-5196-5P | 100.00 | 67.98 | 2761 |
| HSA-MIR-6876-5P | 100.00 | 67.68 | 2126 |
| HSA-MIR-3646 | 100.00 | 73.56 | 5283 |
| HSA-MIR-5193 | 100.00 | 67.26 | 1744 |
| HSA-MIR-4476 | 100.00 | 68.18 | 2030 |
| HSA-MIR-4510 | 100.00 | 66.60 | 2050 |
| HSA-MIR-6127 | 100.00 | 66.76 | 2188 |
| HSA-MIR-6129 | 100.00 | 66.46 | 2080 |
| HSA-MIR-6130 | 100.00 | 66.69 | 2012 |
| HSA-MIR-6133 | 100.00 | 66.48 | 2064 |
| HSA-LET-7A-3P | 100.00 | 74.03 | 3932 |
| HSA-LET-7B-3P | 100.00 | 74.08 | 3913 |
| HSA-LET-7F-1-3P | 100.00 | 74.02 | 3928 |
| HSA-MIR-98-3P | 100.00 | 74.08 | 3907 |
| HSA-MIR-4673 | 100.00 | 66.64 | 1490 |
| HSA-MIR-4682 | 100.00 | 68.89 | 1258 |
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
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | sp1 | ENSDARG00000088347 |
| ENSDARG00000113284 | ||
| mus_musculus | Sp1 | ENSMUSG00000001280 |
| rattus_norvegicus | Sp1 | ENSRNOG00000014084 |
| drosophila_melanogaster | pad | FBGN0038418 |
| drosophila_melanogaster | Spps | FBGN0039169 |
Paralogs (3): SP4 (ENSG00000105866), SP2 (ENSG00000167182), SP3 (ENSG00000172845)
Protein
Protein identifiers
Transcription factor Sp1 — P08047 (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 ID | Names | Canonical? |
|---|---|---|
| P08047-1 | 1, Sp1a | yes |
| P08047-2 | 2, Sp1b | |
| P08047-3 | 3, Sp1c |
RefSeq proteins (3): NP_001238754, NP_003100, NP_612482* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR013087 | Znf_C2H2_type | Domain |
| IPR036236 | Znf_C2H2_sf | Homologous_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.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 1SP1 | SOLUTION NMR | |
| 1SP2 | SOLUTION NMR | |
| 1VA1 | SOLUTION NMR | |
| 1VA2 | SOLUTION NMR | |
| 1VA3 | SOLUTION NMR | |
| 6PV0 | SOLUTION NMR | |
| 6PV1 | SOLUTION NMR | |
| 6PV2 | SOLUTION NMR | |
| 6PV3 | SOLUTION NMR | |
| 6UCO | SOLUTION NMR | |
| 6UCP | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P08047-F1 | 39.98 | 0.01 |
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):
| Position | Phenotype |
|---|---|
| 7 | increase in protein stability. no change in sumoylation. |
| 15 | enhanced transcriptional activity. |
| 16 | loss of sumoylation. no cleavage and reduced transcriptional activity. |
| 18 | loss of sumoylation. increased cleavage and enhanced transcriptional activity. |
| 19 | no effect on sumoylation nor on proteolytic cleavage. |
| 36 | no effect on phosphorylation on dna damage. |
| 56 | no effect on phosphorylation on dna damage. |
| 59 | loss of phosphorylation. no effect on activated mapk8-mediated phosphorylation. similar loss of phosphorylation as by de |
| 59 | some association with chromatin, increased phosphorylation levels and decreased glycosylation. |
| 73 | little effect on activated mapk8-mediated phosphorylation. |
| 81 | no effect on phosphorylation on dna damage. |
| 85 | no effect on phosphorylation on dna damage. |
| 98 | no effect on phosphorylation on dna damage. |
| 101 | significant reduction of phosphorylation on dna damage. |
| 101 | increase in phosphorylation on dna damage. |
| 117 | no effect on activated mapk8-mediated phosphorylation. |
| 220 | no effect on dephosphorylation by pp2a. |
| 250 | no effect on phosphorylation on dna damage. |
| 278 | almost complete abolition of activated mapk8-mediated phosphorylation and 40% reduction in protein levels during mitosis |
| 278 | increased protein stability during mitosis; when associated with d-739. |
| 281 | no effect on phosphorylation on dna damage. |
| 291 | no effect on phosphorylation on dna damage. |
| 296 | no effect on phosphorylation on dna damage. |
| 313 | no effect on phosphorylation on dna damage. |
| 351 | no effect on phosphorylation on dna damage. |
Function
Pathways and Gene Ontology
Reactome pathways
45 pathways
| ID | Pathway |
|---|---|
| R-HSA-1989781 | PPARA activates gene expression |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription |
| R-HSA-2426168 | Activation of gene expression by SREBF (SREBP) |
| R-HSA-2559585 | Oncogene Induced Senescence |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes |
| R-HSA-9018519 | Estrogen-dependent gene expression |
| R-HSA-9735871 | SARS-CoV-1 targets host intracellular signalling and regulatory pathways |
| R-HSA-9762293 | Regulation of CDH11 gene transcription |
| R-HSA-9764790 | Positive Regulation of CDH1 Gene Transcription |
| R-HSA-9818030 | NFE2L2 regulating tumorigenic genes |
| R-HSA-9839394 | TGFBR3 expression |
| R-HSA-1430728 | Metabolism |
| R-HSA-1500931 | Cell-Cell communication |
| R-HSA-162582 | Signal Transduction |
| R-HSA-1643685 | Disease |
| R-HSA-1655829 | Regulation of cholesterol biosynthesis by SREBP (SREBF) |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex |
| R-HSA-212436 | Generic Transcription Pathway |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer |
| R-HSA-2262752 | Cellular responses to stress |
| R-HSA-2559583 | Cellular Senescence |
| R-HSA-400206 | Regulation of lipid metabolism by PPARalpha |
| R-HSA-418990 | Adherens junctions interactions |
| R-HSA-421270 | Cell-cell junction organization |
| R-HSA-446728 | Cell junction organization |
| R-HSA-556833 | Metabolism of lipids |
| R-HSA-5663205 | Infectious disease |
| R-HSA-73857 | RNA Polymerase II Transcription |
| R-HSA-74160 | Gene expression (Transcription) |
| R-HSA-8939211 | ESR-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:
| Category | Pathways |
|---|---|
| RNA Polymerase II Transcription | 2 |
| Regulation of lipid metabolism by PPARalpha | 1 |
| Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 1 |
| Regulation of cholesterol biosynthesis by SREBP (SREBF) | 1 |
| Cellular Senescence | 1 |
| ESR-mediated signaling | 1 |
| SARS-CoV-1-host interactions | 1 |
| Regulation of CDH11 Expression and Function | 1 |
| Regulation of CDH1 Gene Transcription | 1 |
| Nuclear events mediated by NFE2L2 | 1 |
| Signaling by TGFBR3 | 1 |
| Metabolism of steroids | 1 |
| Signaling by TGFB family members | 1 |
| Signaling by TGF-beta Receptor Complex | 1 |
| Generic Transcription Pathway | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| regulation of DNA-templated transcription | 3 |
| RNA polymerase II transcription regulatory region sequence-specific DNA binding | 3 |
| cellular anatomical structure | 3 |
| DNA-templated transcription | 2 |
| regulation of gene expression | 2 |
| transcription by RNA polymerase II | 2 |
| regulation of transcription by RNA polymerase II | 2 |
| transcription cis-regulatory region binding | 2 |
| chromatin | 2 |
| DNA binding | 2 |
| enzyme binding | 2 |
| DNA-binding transcription factor binding | 2 |
| binding | 2 |
| regulation of RNA biosynthetic process | 1 |
| gene expression | 1 |
| positive regulation of macromolecule biosynthetic process | 1 |
| response to insulin | 1 |
| cellular response to peptide hormone stimulus | 1 |
| response to oxidative stress | 1 |
| response to oxygen-containing compound | 1 |
| cellular response to starvation | 1 |
| response to zinc ion starvation | 1 |
| positive regulation of endothelial cell migration | 1 |
| blood vessel endothelial cell migration | 1 |
| regulation of blood vessel endothelial cell migration | 1 |
| host-mediated perturbation of viral transcription | 1 |
| host-mediated activation of viral process | 1 |
| angiogenesis | 1 |
| regulation of angiogenesis | 1 |
| positive regulation of vasculature development | 1 |
| positive regulation of RNA biosynthetic process | 1 |
| positive regulation of DNA-templated transcription | 1 |
| biological_process | 1 |
| cellular response to hormone stimulus | 1 |
| response to estrogen | 1 |
| amyloid-beta formation | 1 |
| regulation of amyloid-beta formation | 1 |
| positive regulation of amyloid precursor protein catabolic process | 1 |
| cellular response to ketone | 1 |
| response to wortmannin | 1 |
Protein interactions and networks
STRING
3280 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| SP1 | ESR1 | P03372 | 979 |
| SP1 | EP300 | Q09472 | 969 |
| SP1 | TP53 | P04637 | 928 |
| SP1 | TBP | P20226 | 900 |
| SP1 | E2F1 | Q01094 | 884 |
| SP1 | MYC | P01106 | 883 |
| SP1 | HTT | P42858 | 849 |
| SP1 | CREBBP | Q92793 | 845 |
| SP1 | JUN | P05412 | 827 |
| SP1 | SMAD2 | Q15796 | 791 |
| SP1 | EPAS1 | Q99814 | 787 |
| SP1 | ESR2 | Q92731 | 786 |
| SP1 | HDAC1 | Q13547 | 780 |
| SP1 | SMAD3 | P84022 | 774 |
| SP1 | HIF1A | Q16665 | 771 |
IntAct
213 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| STAT3 | psi-mi:“MI:0914”(association) | 0.730 | |
| POU2F1 | SP1 | psi-mi:“MI:0915”(physical association) | 0.720 |
| SP1 | POU2F1 | psi-mi:“MI:0915”(physical association) | 0.720 |
| POU2F1 | SP1 | psi-mi:“MI:0407”(direct interaction) | 0.720 |
| SP1 | POU2F1 | psi-mi:“MI:0407”(direct interaction) | 0.720 |
| SP1 | HCFC1 | psi-mi:“MI:0915”(physical association) | 0.680 |
| SP1 | STAT3 | psi-mi:“MI:0915”(physical association) | 0.650 |
| SP1 | STAT3 | psi-mi:“MI:2364”(proximity) | 0.650 |
| SREBF2 | SP1 | psi-mi:“MI:0915”(physical association) | 0.630 |
| SP1 | SREBF2 | psi-mi:“MI:0915”(physical association) | 0.630 |
| SP1 | psi-mi:“MI:0407”(direct interaction) | 0.600 | |
| SP1 | psi-mi:“MI:0914”(association) | 0.600 | |
| SP1 | DLX4 | psi-mi:“MI:0915”(physical association) | 0.600 |
| DLX4 | SP1 | psi-mi:“MI:0407”(direct interaction) | 0.600 |
| FHL2 | SP1 | psi-mi:“MI:0407”(direct interaction) | 0.590 |
| TP53 | SP1 | psi-mi:“MI:0915”(physical association) | 0.590 |
| SP1 | TP53 | psi-mi:“MI:0915”(physical association) | 0.590 |
| SP1 | vp3 | psi-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.
| A | Effect | B | Mechanism |
|---|---|---|---|
| MAPK1 | up-regulates | SP1 | phosphorylation |
| MAPK3 | up-regulates | SP1 | phosphorylation |
| PRKCZ | up-regulates | SP1 | phosphorylation |
| CDK1 | up-regulates | SP1 | phosphorylation |
| ATM | unknown | SP1 | phosphorylation |
| MAPK8 | up-regulates | SP1 | phosphorylation |
| SP1 | “form complex” | SP1/STAT3 | binding |
| NfKb-p65/p50 | up-regulates | SP1 | binding |
| CyclinB/CDK1 | up-regulates | SP1 | phosphorylation |
| SP1 | “up-regulates activity” | CRX | binding |
| SP1 | “up-regulates quantity by expression” | RHO | “transcriptional regulation” |
| TFAP4 | “up-regulates activity” | SP1 | binding |
| ERK1/2 | “up-regulates activity” | SP1 | phosphorylation |
| PPP2CA | “up-regulates activity” | SP1 | dephosphorylation |
| MAPK3 | “up-regulates activity” | SP1 | phosphorylation |
| CSNK2A1 | “down-regulates activity” | SP1 | phosphorylation |
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:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| Downstream signal transduction | 5 | 22.1× | 4e-04 |
| Transcriptional regulation by RUNX3 | 5 | 15.8× | 1e-03 |
| Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells) | 9 | 15.3× | 5e-06 |
| FCGR3A-mediated phagocytosis | 7 | 15.2× | 1e-04 |
| Cyclin D associated events in G1 | 5 | 13.6× | 2e-03 |
| Regulation of PTEN gene transcription | 6 | 12.4× | 1e-03 |
| Transcriptional regulation by RUNX1 | 7 | 11.9× | 4e-04 |
| Regulation of actin dynamics for phagocytic cup formation | 5 | 10.7× | 4e-03 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| positive regulation of miRNA transcription | 12 | 34.5× | 3e-13 |
| embryonic digit morphogenesis | 6 | 17.9× | 1e-04 |
| ephrin receptor signaling pathway | 5 | 17.0× | 1e-03 |
| cellular response to hydrogen peroxide | 7 | 16.2× | 4e-05 |
| cellular response to transforming growth factor beta stimulus | 5 | 13.7× | 3e-03 |
| DNA-templated transcription | 5 | 11.1× | 5e-03 |
| BMP signaling pathway | 5 | 9.9× | 7e-03 |
| response to hypoxia | 8 | 7.6× | 1e-03 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
72 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 61 |
| Likely benign | 4 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
1012 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 12:53380296:GCG:G | donor_gain | 1.0000 |
| 12:53381809:GGCAG:G | donor_gain | 1.0000 |
| 12:53381810:GCAG:G | donor_gain | 1.0000 |
| 12:53381810:GCAGG:G | donor_gain | 1.0000 |
| 12:53381811:CAGGT:C | donor_loss | 1.0000 |
| 12:53381814:G:C | donor_loss | 1.0000 |
| 12:53381815:T:A | donor_loss | 1.0000 |
| 12:53382103:C:A | acceptor_gain | 1.0000 |
| 12:53406577:A:AG | acceptor_gain | 1.0000 |
| 12:53406581:TCA:T | acceptor_loss | 1.0000 |
| 12:53406583:A:AG | acceptor_gain | 1.0000 |
| 12:53406583:A:T | acceptor_loss | 1.0000 |
| 12:53406583:AG:A | acceptor_gain | 1.0000 |
| 12:53406583:AGGT:A | acceptor_gain | 1.0000 |
| 12:53406584:G:A | acceptor_gain | 1.0000 |
| 12:53406584:G:GG | acceptor_gain | 1.0000 |
| 12:53406584:GGT:G | acceptor_gain | 1.0000 |
| 12:53406584:GGTG:G | acceptor_gain | 1.0000 |
| 12:53406584:GGTGA:G | acceptor_gain | 1.0000 |
| 12:53406749:GGAAG:G | donor_gain | 1.0000 |
| 12:53406750:GAAG:G | donor_gain | 1.0000 |
| 12:53406750:GAAGG:G | donor_gain | 1.0000 |
| 12:53406751:A:T | donor_gain | 1.0000 |
| 12:53406751:AAG:A | donor_gain | 1.0000 |
| 12:53406752:AG:A | donor_gain | 1.0000 |
| 12:53406752:AGGTG:A | donor_loss | 1.0000 |
| 12:53406753:GG:G | donor_gain | 1.0000 |
| 12:53406754:G:GG | donor_gain | 1.0000 |
| 12:53406754:GTG:G | donor_loss | 1.0000 |
| 12:53409359:CAG:C | acceptor_loss | 1.0000 |
AlphaMissense
5113 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 12:53409399:T:A | C628S | 1.000 |
| 12:53409399:T:C | C628R | 1.000 |
| 12:53409400:G:A | C628Y | 1.000 |
| 12:53409400:G:C | C628S | 1.000 |
| 12:53409401:C:G | C628W | 1.000 |
| 12:53409414:T:A | C633S | 1.000 |
| 12:53409414:T:C | C633R | 1.000 |
| 12:53409415:G:C | C633S | 1.000 |
| 12:53409445:T:C | L643P | 1.000 |
| 12:53409453:C:A | H646N | 1.000 |
| 12:53409453:C:G | H646D | 1.000 |
| 12:53409455:C:A | H646Q | 1.000 |
| 12:53409455:C:G | H646Q | 1.000 |
| 12:53409459:C:A | R648S | 1.000 |
| 12:53409489:T:C | C658R | 1.000 |
| 12:53409491:T:G | C658W | 1.000 |
| 12:53409516:T:C | F667L | 1.000 |
| 12:53409517:T:C | F667S | 1.000 |
| 12:53409518:C:A | F667L | 1.000 |
| 12:53409518:C:G | F667L | 1.000 |
| 12:53409522:C:A | R669S | 1.000 |
| 12:53409528:G:C | D671H | 1.000 |
| 12:53409529:A:T | D671V | 1.000 |
| 12:53409535:T:C | L673P | 1.000 |
| 12:53409541:G:T | R675M | 1.000 |
| 12:53409542:G:C | R675S | 1.000 |
| 12:53409542:G:T | R675S | 1.000 |
| 12:53409543:C:A | H676N | 1.000 |
| 12:53409543:C:G | H676D | 1.000 |
| 12:53409544:A:C | H676P | 1.000 |
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):
| Study | Trait | p-value |
|---|---|---|
| GCST002942_9 | Percentage gas trapping | 6.000000e-07 |
| GCST004601_163 | Red blood cell count | 1.000000e-10 |
| GCST004622_118 | Reticulocyte count | 2.000000e-10 |
| GCST004633_25 | Neutrophil percentage of white cells | 3.000000e-10 |
| GCST005993_56 | Mean corpuscular hemoglobin | 3.000000e-15 |
| GCST006011_86 | Mean corpuscular volume | 3.000000e-15 |
| GCST006153_2 | Parkinsonism in frontotemporal lobe dementia | 8.000000e-06 |
| GCST006418_11 | Progressive supranuclear palsy | 4.000000e-07 |
| GCST006418_2 | Progressive supranuclear palsy | 4.000000e-07 |
| GCST009672_1 | Hypospadias (moderate to severe) | 4.000000e-09 |
| GCST010243_150 | Apolipoprotein B levels | 1.000000e-08 |
| GCST90002385_228 | High light scatter reticulocyte count | 1.000000e-10 |
| GCST90002392_384 | Mean corpuscular volume | 2.000000e-30 |
| GCST90002397_202 | Mean spheric corpuscular volume | 1.000000e-40 |
| GCST90002403_450 | Red blood cell count | 1.000000e-34 |
| GCST90002405_304 | Reticulocyte count | 3.000000e-18 |
| GCST90002406_336 | Reticulocyte fraction of red cells | 1.000000e-10 |
EFO canonical traits (6, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0007628 | gas trapping measurement |
| EFO:0004305 | erythrocyte count |
| EFO:0007986 | reticulocyte count |
| EFO:0007990 | neutrophil percentage of leukocytes |
| EFO:0004527 | mean corpuscular hemoglobin |
| EFO:0004615 | apolipoprotein 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).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL2105734 | SEPANTRONIUM BROMIDE | 2 | 366 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
PharmGKB clinical annotations
2 annotations.
| Variant | Type | Level | Drugs | Phenotypes |
|---|---|---|---|---|
| rs2683511 | Efficacy,Metabolism/PK | 3 | metformin | Diabetes Mellitus |
| rs784888 | Efficacy,Metabolism/PK | 3 | metformin | Diabetes Mellitus;Type 2 |
PharmGKB variants
2 variants.
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs784888 | AMHR2, SP1 | 3 | 2.50 | 1 | metformin |
| rs2683511 | SP1 | 3 | 3.50 | 1 | metformin |
ChEMBL bioactivities
1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 8.10 | IC50 | 8 | nM | SEPANTRONIUM 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.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 1-(2-methoxyethyl)-2-methyl-3-(pyrazin-2-ylmethyl)benzo[f]benzimidazol-3-ium-4,9-dione bromide | 2025419: Inhibition of human SP1 transfected in PC-3 cells by renilla luciferase reporter gene assay | ic50 | 0.0080 | uM |
CTD chemical–gene interactions
194 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Arsenic Trioxide | affects methylation, decreases reaction, increases reaction, affects binding, increases expression (+3 more) | 9 |
| Quercetin | affects cotreatment, increases activity, affects reaction, increases expression, decreases expression (+3 more) | 8 |
| mithramycin A | decreases expression, decreases reaction, increases activity, affects binding, increases reaction (+1 more) | 7 |
| trichostatin A | decreases reaction, increases activity, affects binding, affects cotreatment, increases reaction (+3 more) | 6 |
| Resveratrol | decreases acetylation, affects binding, increases reaction, decreases activity, affects localization (+5 more) | 6 |
| Doxorubicin | increases phosphorylation, affects activity, affects binding, increases reaction, decreases expression (+3 more) | 6 |
| Tretinoin | increases expression, increases reaction, affects binding, increases activity | 6 |
| Decitabine | affects binding, affects cotreatment, increases reaction, increases expression | 5 |
| Cadmium | decreases reaction, increases reaction, decreases activity, affects reaction, decreases expression (+2 more) | 5 |
| Hydrogen Peroxide | increases reaction, decreases expression, decreases reaction, affects expression, affects binding (+3 more) | 5 |
| Copper Sulfate | decreases reaction, increases expression, affects binding, decreases activity, decreases expression | 5 |
| sodium arsenite | affects binding, increases abundance, increases expression, affects reaction, decreases expression (+1 more) | 4 |
| Acetylcysteine | decreases expression, decreases reaction, increases expression | 4 |
| Copper | decreases abundance, increases expression, increases reaction, decreases reaction, affects abundance (+1 more) | 4 |
| Estradiol | affects cotreatment, increases expression, affects binding, increases reaction, decreases expression (+2 more) | 4 |
| Plicamycin | affects binding, decreases reaction, increases expression, decreases activity | 4 |
| nickel chloride | affects binding, affects cotreatment, increases reaction, increases expression, decreases reaction (+2 more) | 3 |
| cordycepin | affects metabolic processing, affects binding, decreases reaction, decreases expression, increases activity | 3 |
| 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole | affects cotreatment, decreases expression, affects binding, decreases reaction, increases reaction (+1 more) | 3 |
| U 0126 | decreases expression, increases reaction, decreases reaction, increases expression, increases activity | 3 |
| Camptothecin | increases expression, affects localization, increases activity, affects reaction, decreases reaction | 3 |
| Metformin | decreases reaction, increases expression, decreases expression, affects binding, affects cotreatment (+1 more) | 3 |
| Tetrachlorodibenzodioxin | affects binding, increases reaction, increases expression, decreases reaction, increases phosphorylation | 3 |
| Tetradecanoylphorbol Acetate | affects localization, affects binding, increases reaction, increases expression, increases activity (+1 more) | 3 |
| Valproic Acid | affects binding, increases reaction, decreases expression | 3 |
| bisphenol A | increases expression, affects cotreatment | 2 |
| deoxynivalenol | affects expression, affects binding, increases reaction, increases phosphorylation, increases expression | 2 |
| indole-3-carbinol | affects binding, decreases reaction, decreases activity | 2 |
| tetrathiomolybdate | affects binding, increases reaction, decreases abundance, increases expression, increases activity | 2 |
| benzyloxycarbonylleucyl-leucyl-leucine aldehyde | decreases expression, decreases reaction | 2 |
ChEMBL screening assays
10 unique, capped per target: 8 binding, 2 admet
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1058704 | Binding | Inhibition of SP1-dependent luciferase expression | Scuteflorins A and B, dihydropyranocoumarins from Scutellaria lateriflora. — J Nat Prod |
| CHEMBL3061786 | ADMET | Inhibition of Sp1 (unknown origin) by luciferase reporter gene assay | Synthesis 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):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B2H3 | Abcam HeLa SP1 KO | Cancer cell line | Female |
| CVCL_B8Q1 | Abcam HCT 116 SP1 KO | Cancer cell line | Male |
| CVCL_B9BS | Abcam MCF-7 SP1 KO | Cancer cell line | Female |
| CVCL_B9SH | Abcam A-549 SP1 KO | Cancer cell line | Male |
| CVCL_D8BB | Ubigene A-549 SP1 KO | Cancer cell line | Male |
| CVCL_D8W2 | Ubigene HCT 116 SP1 KO | Cancer cell line | Male |
| CVCL_D9ST | Ubigene HEK293 SP1 KO | Transformed cell line | Female |
| CVCL_E0PS | Ubigene HeLa SP1 KO | Cancer cell line | Female |
| CVCL_TQ04 | HAP1 SP1 (-) | Cancer cell line | Male |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): hypospadias, Parkinson disease, progressive supranuclear palsy