TISIDB

Summary
Symbol	SP1
Name	Sp1 transcription factor
Aliases	specificity protein 1; Transcription factor Sp1
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus. Cytoplasm. Note=Nuclear location is governed by glycosylated/phosphorylated states. Insulin promotes nuclear location, while glucagon favors cytoplasmic location.
Domain	-
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). Binds also the PDGFR-alpha G-box promoter. May have a role in modulating the cellular response to DNA damage. Implicated in chromatin remodeling. Plays an essential role in the regulation of FE65 gene expression. In complex with ATF7IP, maintains telomerase activity in cancer cells by inducing TERT and TERC gene expression. Isoform 3 is a stronger activator of transcription than isoform 1. Positively regulates the transcription of the core clock component ARNTL/BMAL1 (PubMed:10391891, PubMed:11371615, PubMed:11904305, PubMed:14593115, PubMed:16377629, PubMed:16478997, PubMed:16943418, PubMed:17049555, PubMed:18171990, PubMed:18199680, PubMed:18239466, PubMed:18513490, PubMed:18619531, PubMed:19193796, PubMed:20091743, PubMed:21798247). Plays a role in the recruitment of SMARCA4/BRG1 on the c-FOS promoter. Plays a role in protecting cells against oxidative stress following brain injury by regulating the expression of RNF112 (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0006790 sulfur compound metabolic process GO:0009301 snRNA transcription GO:0016073 snRNA metabolic process GO:0019058 viral life cycle GO:0019080 viral gene expression GO:0019083 viral transcription GO:0032868 response to insulin GO:0032869 cellular response to insulin stimulus GO:0035821 modification of morphology or physiology of other organism GO:0036166 phenotypic switching GO:0042762 regulation of sulfur metabolic process GO:0042795 snRNA transcription from RNA polymerase II promoter GO:0043434 response to peptide hormone GO:0043900 regulation of multi-organism process GO:0043902 positive regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0043921 modulation by host of viral transcription GO:0043923 positive regulation by host of viral transcription GO:0044033 multi-organism metabolic process GO:0044272 sulfur compound biosynthetic process GO:0046782 regulation of viral transcription GO:0048511 rhythmic process GO:0048524 positive regulation of viral process GO:0050434 positive regulation of viral transcription GO:0050792 regulation of viral process GO:0051176 positive regulation of sulfur metabolic process GO:0051702 interaction with symbiont GO:0051817 modification of morphology or physiology of other organism involved in symbiotic interaction GO:0051851 modification by host of symbiont morphology or physiology GO:0052312 modulation of transcription in other organism involved in symbiotic interaction GO:0052472 modulation by host of symbiont transcription GO:0070813 hydrogen sulfide metabolic process GO:0070814 hydrogen sulfide biosynthetic process GO:0071375 cellular response to peptide hormone stimulus GO:0071417 cellular response to organonitrogen compound GO:0098781 ncRNA transcription GO:0100057 regulation of phenotypic switching by transcription from RNA polymerase II promoter GO:1900239 regulation of phenotypic switching GO:1901652 response to peptide GO:1901653 cellular response to peptide GO:1903900 regulation of viral life cycle GO:1903902 positive regulation of viral life cycle GO:1904826 regulation of hydrogen sulfide biosynthetic process GO:1904828 positive regulation of hydrogen sulfide biosynthetic process
Molecular Function	GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001046 core promoter sequence-specific DNA binding GO:0001047 core promoter binding GO:0001085 RNA polymerase II transcription factor binding GO:0001103 RNA polymerase II repressing transcription factor binding GO:0001159 core promoter proximal region DNA binding GO:0008022 protein C-terminus binding GO:0008134 transcription factor binding GO:0035035 histone acetyltransferase binding GO:0042826 histone deacetylase binding GO:0043425 bHLH transcription factor binding GO:0070491 repressing transcription factor binding GO:0071837 HMG box domain binding
Cellular Component	GO:0000785 chromatin GO:0000790 nuclear chromatin GO:0032993 protein-DNA complex GO:0044454 nuclear chromosome part

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04350 TGF-beta signaling pathway hsa04915 Estrogen signaling pathway
Reactome	R-HSA-2426168: Activation of gene expression by SREBF (SREBP) R-HSA-2559583: Cellular Senescence R-HSA-2262752: Cellular responses to stress R-HSA-535734: Fatty acid, triacylglycerol, and ketone body metabolism R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-2559585: Oncogene Induced Senescence R-HSA-1989781: PPARA activates gene expression R-HSA-6807505: RNA polymerase II transcribes snRNA genes R-HSA-1655829: Regulation of cholesterol biosynthesis by SREBP (SREBF) R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) R-HSA-2173796: SMAD2/SMAD3 R-HSA-162582: Signal Transduction R-HSA-170834: Signaling by TGF-beta Receptor Complex R-HSA-2173793: Transcriptional activity of SMAD2/SMAD3

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04350 TGF-beta signaling pathway
hsa04915 Estrogen signaling pathway

Reactome

R-HSA-2426168: Activation of gene expression by SREBF (SREBP)
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-535734: Fatty acid, triacylglycerol, and ketone body metabolism
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-2559585: Oncogene Induced Senescence
R-HSA-1989781: PPARA activates gene expression
R-HSA-6807505: RNA polymerase II transcribes snRNA genes
R-HSA-1655829: Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-2173796: SMAD2/SMAD3
R-HSA-162582: Signal Transduction
R-HSA-170834: Signaling by TGF-beta Receptor Complex
R-HSA-2173793: Transcriptional activity of SMAD2/SMAD3

Summary
Symbol	SP1
Name	Sp1 transcription factor
Aliases	specificity protein 1; Transcription factor Sp1
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SP1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between SP1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28574228	Cholangiocarcinoma	Inhibit immunity	P-Sp1 also regulated aPKC-ι/Snail-induced EMT-like changes and immunosuppression in CCA cells.
23509364	Breast Carcinoma; Hepatocellular Carcinoma; Colorectal Carcinoma	Promote immunity	Overexpression of Snail1 and inhibition of glycogen synthase kinase-3β in colorectal tumor cells markedly induced the activity of Sp1 transcription factor, which plays a key role in the upregulation of NKG2DL expression during EMT.

Summary
Symbol	SP1
Name	Sp1 transcription factor
Aliases	specificity protein 1; Transcription factor Sp1
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of SP1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.7	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	SP1
Name	Sp1 transcription factor
Aliases	specificity protein 1; Transcription factor Sp1
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of SP1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.006	0.977
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.127	0.944
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.082	0.95
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.199	0.58
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.166	0.943
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.66	0.822
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.118	0.771
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.234	0.904
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.008	0.997
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.81	0.564
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.336	0.523
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.022	0.722

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SP1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	2.7	-2.7	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	7.7	-7.7	0.371
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	SP1
Name	Sp1 transcription factor
Aliases	specificity protein 1; Transcription factor Sp1
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SP1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	SP1
Name	Sp1 transcription factor
Aliases	specificity protein 1; Transcription factor Sp1
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SP1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SP1
Name	Sp1 transcription factor
Aliases	specificity protein 1; Transcription factor Sp1
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SP1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	SP1
Name	Sp1 transcription factor
Aliases	specificity protein 1; Transcription factor Sp1
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SP1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SP1
Name	Sp1 transcription factor
Aliases	specificity protein 1; Transcription factor Sp1
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SP1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SP1
Name	Sp1 transcription factor
Aliases	specificity protein 1; Transcription factor Sp1
Chromosomal Location	12q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SP1 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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