TISIDB

Summary
Symbol	RPS6KB1
Name	ribosomal protein S6 kinase, 70kDa, polypeptide 1
Aliases	S6K1; p70(S6K)-alpha; PS6K; STK14A; ribosomal protein S6 kinase, 70kD, polypeptide 1; S6K; S6K-beta-1; p70 S ......
Chromosomal Location	17q23.1
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	Cell junction, synapse, synaptosome Mitochondrion outer membrane. Mitochondrion. Note=Colocalizes with URI1 at mitochondrion.; SUBCELLULAR LOCATION: Isoform Alpha I: Nucleus. Cytoplasm.; SUBCELLULAR LOCATION: Isoform Alpha II: Cytoplasm.
Domain	PF00069 Protein kinase domain PF00433 Protein kinase C terminal domain
Function	Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin. Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:23429703). Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (PubMed:28178239).

> Gene Ontology [ TOP ]
Biological Process	GO:0000082 G1/S transition of mitotic cell cycle GO:0001101 response to acid chemical GO:0001662 behavioral fear response GO:0002209 behavioral defense response GO:0002237 response to molecule of bacterial origin GO:0003009 skeletal muscle contraction GO:0003012 muscle system process GO:0006413 translational initiation GO:0006417 regulation of translation GO:0006446 regulation of translational initiation GO:0006936 muscle contraction GO:0006941 striated muscle contraction GO:0007281 germ cell development GO:0007346 regulation of mitotic cell cycle GO:0007517 muscle organ development GO:0007519 skeletal muscle tissue development GO:0007568 aging GO:0007584 response to nutrient GO:0007611 learning or memory GO:0007613 memory GO:0007616 long-term memory GO:0008286 insulin receptor signaling pathway GO:0008643 carbohydrate transport GO:0008645 hexose transport GO:0009266 response to temperature stimulus GO:0009408 response to heat GO:0009612 response to mechanical stimulus GO:0009636 response to toxic substance GO:0009743 response to carbohydrate GO:0009746 response to hexose GO:0009749 response to glucose GO:0009991 response to extracellular stimulus GO:0010608 posttranscriptional regulation of gene expression GO:0010827 regulation of glucose transport GO:0014706 striated muscle tissue development GO:0014732 skeletal muscle atrophy GO:0014812 muscle cell migration GO:0014874 response to stimulus involved in regulation of muscle adaptation GO:0014878 response to electrical stimulus involved in regulation of muscle adaptation GO:0014888 striated muscle adaptation GO:0014889 muscle atrophy GO:0014891 striated muscle atrophy GO:0014909 smooth muscle cell migration GO:0014910 regulation of smooth muscle cell migration GO:0014911 positive regulation of smooth muscle cell migration GO:0015749 monosaccharide transport GO:0015758 glucose transport GO:0016202 regulation of striated muscle tissue development GO:0022412 cellular process involved in reproduction in multicellular organism GO:0030335 positive regulation of cell migration GO:0031667 response to nutrient levels GO:0031929 TOR signaling GO:0031960 response to corticosteroid GO:0032496 response to lipopolysaccharide GO:0032868 response to insulin GO:0032869 cellular response to insulin stimulus GO:0033002 muscle cell proliferation GO:0033555 multicellular organismal response to stress GO:0033574 response to testosterone GO:0033762 response to glucagon GO:0034248 regulation of cellular amide metabolic process GO:0034250 positive regulation of cellular amide metabolic process GO:0034284 response to monosaccharide GO:0034612 response to tumor necrosis factor GO:0040017 positive regulation of locomotion GO:0042493 response to drug GO:0042596 fear response GO:0043200 response to amino acid GO:0043201 response to leucine GO:0043434 response to peptide hormone GO:0043491 protein kinase B signaling GO:0043500 muscle adaptation GO:0043501 skeletal muscle adaptation GO:0043502 regulation of muscle adaptation GO:0044057 regulation of system process GO:0044708 single-organism behavior GO:0044770 cell cycle phase transition GO:0044772 mitotic cell cycle phase transition GO:0044843 cell cycle G1/S phase transition GO:0045471 response to ethanol GO:0045727 positive regulation of translation GO:0045787 positive regulation of cell cycle GO:0045844 positive regulation of striated muscle tissue development GO:0045927 positive regulation of growth GO:0045931 positive regulation of mitotic cell cycle GO:0045948 positive regulation of translational initiation GO:0046323 glucose import GO:0046324 regulation of glucose import GO:0046626 regulation of insulin receptor signaling pathway GO:0046627 negative regulation of insulin receptor signaling pathway GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling GO:0048545 response to steroid hormone GO:0048630 skeletal muscle tissue growth GO:0048631 regulation of skeletal muscle tissue growth GO:0048633 positive regulation of skeletal muscle tissue growth GO:0048634 regulation of muscle organ development GO:0048636 positive regulation of muscle organ development GO:0048638 regulation of developmental growth GO:0048639 positive regulation of developmental growth GO:0048641 regulation of skeletal muscle tissue development GO:0048643 positive regulation of skeletal muscle tissue development GO:0048659 smooth muscle cell proliferation GO:0048660 regulation of smooth muscle cell proliferation GO:0048661 positive regulation of smooth muscle cell proliferation GO:0050879 multicellular organismal movement GO:0050881 musculoskeletal movement GO:0050890 cognition GO:0051272 positive regulation of cellular component movement GO:0051384 response to glucocorticoid GO:0051602 response to electrical stimulus GO:0060537 muscle tissue development GO:0060538 skeletal muscle organ development GO:0071375 cellular response to peptide hormone stimulus GO:0071407 cellular response to organic cyclic compound GO:0071417 cellular response to organonitrogen compound GO:0090257 regulation of muscle system process GO:0097191 extrinsic apoptotic signaling pathway GO:0097305 response to alcohol GO:1900076 regulation of cellular response to insulin stimulus GO:1900077 negative regulation of cellular response to insulin stimulus GO:1901652 response to peptide GO:1901653 cellular response to peptide GO:1901654 response to ketone GO:1901861 regulation of muscle tissue development GO:1901863 positive regulation of muscle tissue development GO:2000147 positive regulation of cell motility GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001236 regulation of extrinsic apoptotic signaling pathway GO:2001237 negative regulation of extrinsic apoptotic signaling pathway
Molecular Function	GO:0004674 protein serine/threonine kinase activity GO:0004711 ribosomal protein S6 kinase activity GO:0004712 protein serine/threonine/tyrosine kinase activity GO:0019902 phosphatase binding GO:0019903 protein phosphatase binding GO:0030165 PDZ domain binding GO:0033218 amide binding GO:0042277 peptide binding GO:0051721 protein phosphatase 2A binding
Cellular Component	GO:0005741 mitochondrial outer membrane GO:0019867 outer membrane GO:0031968 organelle outer membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04012 ErbB signaling pathway hsa04066 HIF-1 signaling pathway hsa04140 Regulation of autophagy hsa04150 mTOR signaling pathway hsa04151 PI3K-Akt signaling pathway hsa04152 AMPK signaling pathway hsa04350 TGF-beta signaling pathway hsa04666 Fc gamma R-mediated phagocytosis hsa04910 Insulin signaling pathway
Reactome	R-HSA-2428924: IGF1R signaling cascade R-HSA-112399: IRS-mediated signalling R-HSA-2428928: IRS-related events triggered by IGF1R R-HSA-74751: Insulin receptor signalling cascade R-HSA-109704: PI3K Cascade R-HSA-109703: PKB-mediated events R-HSA-162582: Signal Transduction R-HSA-74752: Signaling by Insulin receptor R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) R-HSA-165159: mTOR signalling R-HSA-166208: mTORC1-mediated signalling

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04012 ErbB signaling pathway
hsa04066 HIF-1 signaling pathway
hsa04140 Regulation of autophagy
hsa04150 mTOR signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04152 AMPK signaling pathway
hsa04350 TGF-beta signaling pathway
hsa04666 Fc gamma R-mediated phagocytosis
hsa04910 Insulin signaling pathway

Reactome

R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-109704: PI3K Cascade
R-HSA-109703: PKB-mediated events
R-HSA-162582: Signal Transduction
R-HSA-74752: Signaling by Insulin receptor
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-165159: mTOR signalling
R-HSA-166208: mTORC1-mediated signalling

Summary
Symbol	RPS6KB1
Name	ribosomal protein S6 kinase, 70kDa, polypeptide 1
Aliases	S6K1; p70(S6K)-alpha; PS6K; STK14A; ribosomal protein S6 kinase, 70kD, polypeptide 1; S6K; S6K-beta-1; p70 S ......
Chromosomal Location	17q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between RPS6KB1 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 [ TOP ]
There is no record.

Summary
Symbol	RPS6KB1
Name	ribosomal protein S6 kinase, 70kDa, polypeptide 1
Aliases	S6K1; p70(S6K)-alpha; PS6K; STK14A; ribosomal protein S6 kinase, 70kD, polypeptide 1; S6K; S6K-beta-1; p70 S ......
Chromosomal Location	17q23.1
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

[ TOP ]

Statistical results of RPS6KB1 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	STARS Score: 4.58; FDR: 0.011	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 4.96; FDR: 0.009	Sensitive to T cell-mediated killing
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	RPS6KB1
Name	ribosomal protein S6 kinase, 70kDa, polypeptide 1
Aliases	S6K1; p70(S6K)-alpha; PS6K; STK14A; ribosomal protein S6 kinase, 70kD, polypeptide 1; S6K; S6K-beta-1; p70 S ......
Chromosomal Location	17q23.1
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

[ TOP ]

Points in the above scatter plot represent the expression difference of RPS6KB1 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	-0.06	0.785
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.223	0.872
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.061	0.95
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.024	0.915
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.136	0.941
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.228	0.924
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.037	0.912
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.112	0.943
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.201	0.909
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.174	0.894
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	-0.251	0.897
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.05	0.253

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of RPS6KB1 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	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
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	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
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	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	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	14.3	-14.3	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	RPS6KB1
Name	ribosomal protein S6 kinase, 70kDa, polypeptide 1
Aliases	S6K1; p70(S6K)-alpha; PS6K; STK14A; ribosomal protein S6 kinase, 70kD, polypeptide 1; S6K; S6K-beta-1; p70 S ......
Chromosomal Location	17q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RPS6KB1. 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	RPS6KB1
Name	ribosomal protein S6 kinase, 70kDa, polypeptide 1
Aliases	S6K1; p70(S6K)-alpha; PS6K; STK14A; ribosomal protein S6 kinase, 70kD, polypeptide 1; S6K; S6K-beta-1; p70 S ......
Chromosomal Location	17q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RPS6KB1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RPS6KB1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	RPS6KB1
Name	ribosomal protein S6 kinase, 70kDa, polypeptide 1
Aliases	S6K1; p70(S6K)-alpha; PS6K; STK14A; ribosomal protein S6 kinase, 70kD, polypeptide 1; S6K; S6K-beta-1; p70 S ......
Chromosomal Location	17q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RPS6KB1. 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	RPS6KB1
Name	ribosomal protein S6 kinase, 70kDa, polypeptide 1
Aliases	S6K1; p70(S6K)-alpha; PS6K; STK14A; ribosomal protein S6 kinase, 70kD, polypeptide 1; S6K; S6K-beta-1; p70 S ......
Chromosomal Location	17q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of RPS6KB1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	RPS6KB1
Name	ribosomal protein S6 kinase, 70kDa, polypeptide 1
Aliases	S6K1; p70(S6K)-alpha; PS6K; STK14A; ribosomal protein S6 kinase, 70kD, polypeptide 1; S6K; S6K-beta-1; p70 S ......
Chromosomal Location	17q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between RPS6KB1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	RPS6KB1
Name	ribosomal protein S6 kinase, 70kDa, polypeptide 1
Aliases	S6K1; p70(S6K)-alpha; PS6K; STK14A; ribosomal protein S6 kinase, 70kD, polypeptide 1; S6K; S6K-beta-1; p70 S ......
Chromosomal Location	17q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting RPS6KB1 collected from DrugBank database.

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

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