TISIDB

Summary
Symbol	FOS
Name	FBJ murine osteosarcoma viral oncogene homolog
Aliases	c-fos; v-fos FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral (v-fos) oncogene ......
Chromosomal Location	14q24.3
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. Endoplasmic reticulum. Cytoplasm, cytosol. Note=In quiescent cells, present in very small amounts in the cytosol. Following induction of cell growth, first localizes to the endoplasmic reticulum and only later to the nucleus. Localization at the endoplasmic reticulum requires dephosphorylation at Tyr-10 and Tyr-30.
Domain	PF00170 bZIP transcription factor
Function	Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum.

> Gene Ontology [ TOP ]
Biological Process	GO:0000302 response to reactive oxygen species GO:0001661 conditioned taste aversion GO:0002237 response to molecule of bacterial origin GO:0002521 leukocyte differentiation GO:0002573 myeloid leukocyte differentiation GO:0002761 regulation of myeloid leukocyte differentiation GO:0002763 positive regulation of myeloid leukocyte differentiation GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0006304 DNA modification GO:0006305 DNA alkylation GO:0006306 DNA methylation GO:0006979 response to oxidative stress GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007179 transforming growth factor beta receptor signaling pathway GO:0007517 muscle organ development GO:0007519 skeletal muscle tissue development GO:0007565 female pregnancy GO:0007568 aging GO:0007611 learning or memory GO:0007612 learning GO:0007631 feeding behavior GO:0008306 associative learning GO:0009266 response to temperature stimulus GO:0009314 response to radiation GO:0009409 response to cold GO:0009416 response to light stimulus GO:0009612 response to mechanical stimulus GO:0009629 response to gravity GO:0009636 response to toxic substance GO:0009991 response to extracellular stimulus GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0014074 response to purine-containing compound GO:0014706 striated muscle tissue development GO:0030099 myeloid cell differentiation GO:0030316 osteoclast differentiation GO:0030431 sleep GO:0031668 cellular response to extracellular stimulus GO:0031960 response to corticosteroid GO:0032259 methylation GO:0032496 response to lipopolysaccharide GO:0032570 response to progesterone GO:0034599 cellular response to oxidative stress GO:0034614 cellular response to reactive oxygen species GO:0035902 response to immobilization stress GO:0035914 skeletal muscle cell differentiation GO:0035994 response to muscle stretch GO:0038093 Fc receptor signaling pathway GO:0038095 Fc-epsilon receptor signaling pathway GO:0042493 response to drug GO:0043414 macromolecule methylation GO:0044706 multi-multicellular organism process GO:0044708 single-organism behavior GO:0044728 DNA methylation or demethylation GO:0045637 regulation of myeloid cell differentiation GO:0045639 positive regulation of myeloid cell differentiation GO:0045670 regulation of osteoclast differentiation GO:0045672 positive regulation of osteoclast differentiation GO:0046683 response to organophosphorus GO:0048545 response to steroid hormone GO:0050890 cognition GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051384 response to glucocorticoid GO:0051385 response to mineralocorticoid GO:0051412 response to corticosterone GO:0051591 response to cAMP GO:0051592 response to calcium ion GO:0060395 SMAD protein signal transduction GO:0060537 muscle tissue development GO:0060538 skeletal muscle organ development GO:0061614 pri-miRNA transcription from RNA polymerase II promoter GO:0071241 cellular response to inorganic substance GO:0071248 cellular response to metal ion GO:0071277 cellular response to calcium ion GO:0071496 cellular response to external stimulus GO:0071559 response to transforming growth factor beta GO:0071560 cellular response to transforming growth factor beta stimulus GO:1901654 response to ketone GO:1902105 regulation of leukocyte differentiation GO:1902107 positive regulation of leukocyte differentiation GO:1902893 regulation of pri-miRNA transcription from RNA polymerase II promoter GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter GO:1903706 regulation of hemopoiesis GO:1903708 positive regulation of hemopoiesis
Molecular Function	GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000979 RNA polymerase II core promoter 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:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001159 core promoter proximal region DNA binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003682 chromatin binding GO:0008134 transcription factor binding GO:0046332 SMAD binding GO:0046982 protein heterodimerization activity GO:0070412 R-SMAD binding
Cellular Component	GO:0005667 transcription factor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04010 MAPK signaling pathway hsa04024 cAMP signaling pathway hsa04210 Apoptosis hsa04380 Osteoclast differentiation hsa04620 Toll-like receptor signaling pathway hsa04660 T cell receptor signaling pathway hsa04662 B cell receptor signaling pathway hsa04668 TNF signaling pathway hsa04713 Circadian entrainment hsa04725 Cholinergic synapse hsa04728 Dopaminergic synapse hsa04915 Estrogen signaling pathway hsa04917 Prolactin signaling pathway hsa04921 Oxytocin signaling pathway
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-450341: Activation of the AP-1 family of transcription factors R-HSA-2559583: Cellular Senescence R-HSA-2262752: Cellular responses to stress R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-2871796: FCERI mediated MAPK activation R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6785807: Interleukin-4 and 13 signaling R-HSA-450294: MAP kinase activation in TLR cascade R-HSA-450282: MAPK targets/ Nuclear events mediated by MAP kinases R-HSA-975871: MyD88 cascade initiated on plasma membrane R-HSA-975155: MyD88 dependent cascade initiated on endosome R-HSA-166166: MyD88-independent TLR3/TLR4 cascade R-HSA-166058: MyD88 R-HSA-2559580: Oxidative Stress Induced Senescence R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP) R-HSA-449147: Signaling by Interleukins R-HSA-6796648: TP53 Regulates Transcription of DNA Repair Genes R-HSA-168180: TRAF6 Mediated Induction of proinflammatory cytokines R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade R-HSA-168176: Toll Like Receptor 5 (TLR5) Cascade R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade R-HSA-168179: Toll Like Receptor TLR1 R-HSA-168188: Toll Like Receptor TLR6 R-HSA-168898: Toll-Like Receptors Cascades R-HSA-3700989: Transcriptional Regulation by TP53

> KEGG and Reactome Pathway

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KEGG

hsa04010 MAPK signaling pathway
hsa04024 cAMP signaling pathway
hsa04210 Apoptosis
hsa04380 Osteoclast differentiation
hsa04620 Toll-like receptor signaling pathway
hsa04660 T cell receptor signaling pathway
hsa04662 B cell receptor signaling pathway
hsa04668 TNF signaling pathway
hsa04713 Circadian entrainment
hsa04725 Cholinergic synapse
hsa04728 Dopaminergic synapse
hsa04915 Estrogen signaling pathway
hsa04917 Prolactin signaling pathway
hsa04921 Oxytocin signaling pathway

Reactome

R-HSA-166054: Activated TLR4 signalling
R-HSA-450341: Activation of the AP-1 family of transcription factors
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-450294: MAP kinase activation in TLR cascade
R-HSA-450282: MAPK targets/ Nuclear events mediated by MAP kinases
R-HSA-975871: MyD88 cascade initiated on plasma membrane
R-HSA-975155: MyD88 dependent cascade initiated on endosome
R-HSA-166166: MyD88-independent TLR3/TLR4 cascade
R-HSA-166058: MyD88
R-HSA-2559580: Oxidative Stress Induced Senescence
R-HSA-2559582: Senescence-Associated Secretory Phenotype (SASP)
R-HSA-449147: Signaling by Interleukins
R-HSA-6796648: TP53 Regulates Transcription of DNA Repair Genes
R-HSA-168180: TRAF6 Mediated Induction of proinflammatory cytokines
R-HSA-975138: TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling
R-HSA-168142: Toll Like Receptor 10 (TLR10) Cascade
R-HSA-181438: Toll Like Receptor 2 (TLR2) Cascade
R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168176: Toll Like Receptor 5 (TLR5) Cascade
R-HSA-168181: Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168138: Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168179: Toll Like Receptor TLR1
R-HSA-168188: Toll Like Receptor TLR6
R-HSA-168898: Toll-Like Receptors Cascades
R-HSA-3700989: Transcriptional Regulation by TP53

Summary
Symbol	FOS
Name	FBJ murine osteosarcoma viral oncogene homolog
Aliases	c-fos; v-fos FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral (v-fos) oncogene ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FOS 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 FOS and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23319273	Prostate Carcinoma	Inhibit immunity	Studies revealed that the levels of expression of genes responsible for T-cell proliferation (C-FOS, C-JUN and DUSP1) and cellular migration (RGS1) were greater in Tregs from mCRPC patients as compared to values observed in healthy donors.

Summary
Symbol	FOS
Name	FBJ murine osteosarcoma viral oncogene homolog
Aliases	c-fos; v-fos FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral (v-fos) oncogene ......
Chromosomal Location	14q24.3
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 FOS 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	NA/NS	NA/NS
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	FOS
Name	FBJ murine osteosarcoma viral oncogene homolog
Aliases	c-fos; v-fos FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral (v-fos) oncogene ......
Chromosomal Location	14q24.3
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 FOS 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	0.092	0.862
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.102	0.972
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.248	0.898
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.743	0.414
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.459	0.883
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.093	0.794
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.224	0.656
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.175	0.917
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.187	0.914
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.331	0.399
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	3.045	0.155
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.373	0.0928

> Mutation difference between responders and non-responders

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

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	11.8	-11.8	0.488
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	FOS
Name	FBJ murine osteosarcoma viral oncogene homolog
Aliases	c-fos; v-fos FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral (v-fos) oncogene ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FOS. 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	FOS
Name	FBJ murine osteosarcoma viral oncogene homolog
Aliases	c-fos; v-fos FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral (v-fos) oncogene ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FOS. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FOS. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FOS
Name	FBJ murine osteosarcoma viral oncogene homolog
Aliases	c-fos; v-fos FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral (v-fos) oncogene ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FOS. 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	FOS
Name	FBJ murine osteosarcoma viral oncogene homolog
Aliases	c-fos; v-fos FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral (v-fos) oncogene ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FOS expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FOS
Name	FBJ murine osteosarcoma viral oncogene homolog
Aliases	c-fos; v-fos FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral (v-fos) oncogene ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FOS and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FOS
Name	FBJ murine osteosarcoma viral oncogene homolog
Aliases	c-fos; v-fos FBJ murine osteosarcoma viral oncogene homolog; FBJ murine osteosarcoma viral (v-fos) oncogene ......
Chromosomal Location	14q24.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FOS collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting FOS.

ID	Name	Drug Type	Targets	#Targets
DB00852	Pseudoephedrine	Small Molecule	ADRA1A, ADRA2A, ADRB1, ADRB2, ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, ......	20
DB08813	Nadroparin	Small Molecule	FOS, MYC, SELP, SERPINC1	4

Browse FOS