TISIDB

Summary
Symbol	RPS6KA5
Name	ribosomal protein S6 kinase, 90kDa, polypeptide 5
Aliases	MSK1; RLPK; ribosomal protein S6 kinase, 90kD, polypeptide 5; MSPK1; 90 kDa ribosomal protein S6 kinase 5; R ......
Chromosomal Location	14q31-q32.1
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=Predominantly nuclear. Exported into cytoplasm in response to glucocorticoid.
Domain	PF00069 Protein kinase domain PF00433 Protein kinase C terminal domain
Function	Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes (PubMed:11909979, PubMed:12569367, PubMed:12763138, PubMed:9687510, PubMed:18511904, PubMed:9873047). Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin (PubMed:11909979, PubMed:9873047). Plays an essential role in the control of RELA transcriptional activity in response to TNF and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression (PubMed:12628924, PubMed:18511904). In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress (PubMed:12628924). In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential (PubMed:12763138). Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation (PubMed:12569367). Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A (PubMed:15010469). Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN (PubMed:12773393). May also phosphorylate 'Ser-28' of histone H3 (PubMed:12773393). Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (PubMed:12773393). In lipopolysaccharide-stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines (By similarity). Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors (By similarity). Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury (By similarity). Phosphorylates TRIM7 at 'Ser-107' in response to growth factor signaling via the MEK/ERK pathway, thereby stimulating its ubiquitin ligase activity (PubMed:25851810).

> Gene Ontology [ TOP ]
Biological Process	GO:0001818 negative regulation of cytokine production GO:0002218 activation of innate immune response GO:0002220 innate immune response activating cell surface receptor signaling pathway GO:0002223 stimulatory C-type lectin receptor signaling pathway GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0006473 protein acetylation GO:0006475 internal protein amino acid acetylation GO:0007173 epidermal growth factor receptor signaling pathway GO:0007409 axonogenesis GO:0007411 axon guidance GO:0016570 histone modification GO:0016572 histone phosphorylation GO:0016573 histone acetylation GO:0018105 peptidyl-serine phosphorylation GO:0018205 peptidyl-lysine modification GO:0018209 peptidyl-serine modification GO:0018393 internal peptidyl-lysine acetylation GO:0018394 peptidyl-lysine acetylation GO:0031056 regulation of histone modification GO:0031058 positive regulation of histone modification GO:0031349 positive regulation of defense response GO:0032793 positive regulation of CREB transcription factor activity GO:0033127 regulation of histone phosphorylation GO:0033129 positive regulation of histone phosphorylation GO:0035065 regulation of histone acetylation GO:0035066 positive regulation of histone acetylation GO:0035404 histone-serine phosphorylation GO:0038127 ERBB signaling pathway GO:0043543 protein acylation GO:0043987 histone H3-S10 phosphorylation GO:0043988 histone H3-S28 phosphorylation GO:0043990 histone H2A-S1 phosphorylation GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0048667 cell morphogenesis involved in neuron differentiation GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0061564 axon development GO:0070498 interleukin-1-mediated signaling pathway GO:0070555 response to interleukin-1 GO:0071347 cellular response to interleukin-1 GO:0097485 neuron projection guidance GO:1901983 regulation of protein acetylation GO:1901985 positive regulation of protein acetylation GO:1902275 regulation of chromatin organization GO:1905269 positive regulation of chromatin organization GO:1990164 histone H2A phosphorylation GO:2000756 regulation of peptidyl-lysine acetylation GO:2000758 positive regulation of peptidyl-lysine acetylation
Molecular Function	GO:0000287 magnesium ion binding GO:0004674 protein serine/threonine kinase activity GO:0035173 histone kinase activity GO:0035174 histone serine kinase activity GO:0035175 histone kinase activity (H3-S10 specific)
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04010 MAPK signaling pathway hsa04261 Adrenergic signaling in cardiomyocytes hsa04668 TNF signaling pathway hsa04713 Circadian entrainment hsa04722 Neurotrophin signaling pathway
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-422475: Axon guidance R-HSA-5621481: C-type lectin receptors (CLRs) R-HSA-5621575: CD209 (DC-SIGN) signaling R-HSA-199920: CREB phosphorylation R-HSA-1266738: Developmental Biology R-HSA-198753: ERK/MAPK targets R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-373760: L1CAM interactions 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-375165: NCAM signaling for neurite out-growth R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-198725: Nuclear Events (kinase and transcription factor activation) R-HSA-437239: Recycling pathway of L1 R-HSA-162582: Signal Transduction R-HSA-166520: Signalling by NGF 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

> KEGG and Reactome Pathway

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KEGG

hsa04010 MAPK signaling pathway
hsa04261 Adrenergic signaling in cardiomyocytes
hsa04668 TNF signaling pathway
hsa04713 Circadian entrainment
hsa04722 Neurotrophin signaling pathway

Reactome

R-HSA-166054: Activated TLR4 signalling
R-HSA-422475: Axon guidance
R-HSA-5621481: C-type lectin receptors (CLRs)
R-HSA-5621575: CD209 (DC-SIGN) signaling
R-HSA-199920: CREB phosphorylation
R-HSA-1266738: Developmental Biology
R-HSA-198753: ERK/MAPK targets
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-373760: L1CAM interactions
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-375165: NCAM signaling for neurite out-growth
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-198725: Nuclear Events (kinase and transcription factor activation)
R-HSA-437239: Recycling pathway of L1
R-HSA-162582: Signal Transduction
R-HSA-166520: Signalling by NGF
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

Summary
Symbol	RPS6KA5
Name	ribosomal protein S6 kinase, 90kDa, polypeptide 5
Aliases	MSK1; RLPK; ribosomal protein S6 kinase, 90kD, polypeptide 5; MSPK1; 90 kDa ribosomal protein S6 kinase 5; R ......
Chromosomal Location	14q31-q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between RPS6KA5 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	RPS6KA5
Name	ribosomal protein S6 kinase, 90kDa, polypeptide 5
Aliases	MSK1; RLPK; ribosomal protein S6 kinase, 90kD, polypeptide 5; MSPK1; 90 kDa ribosomal protein S6 kinase 5; R ......
Chromosomal Location	14q31-q32.1
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 RPS6KA5 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	RPS6KA5
Name	ribosomal protein S6 kinase, 90kDa, polypeptide 5
Aliases	MSK1; RLPK; ribosomal protein S6 kinase, 90kD, polypeptide 5; MSPK1; 90 kDa ribosomal protein S6 kinase 5; R ......
Chromosomal Location	14q31-q32.1
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 RPS6KA5 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	0.842	0.0186
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.419	0.239
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.428	0.602
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.188	0.512
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.324	0.86
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.021	0.992
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.269	0.379
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.063	0.959
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.51	0.708
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.369	0.539
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	1.173	0.116
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.146	0.131

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of RPS6KA5 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	11.1	1.4	9.7	0.0589
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	11.1	1.7	9.4	0.0895
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	12.5	-12.5	0.52
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	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	3.7	-1.1	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	7.1	-7.1	0.467
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	RPS6KA5
Name	ribosomal protein S6 kinase, 90kDa, polypeptide 5
Aliases	MSK1; RLPK; ribosomal protein S6 kinase, 90kD, polypeptide 5; MSPK1; 90 kDa ribosomal protein S6 kinase 5; R ......
Chromosomal Location	14q31-q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RPS6KA5. 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	RPS6KA5
Name	ribosomal protein S6 kinase, 90kDa, polypeptide 5
Aliases	MSK1; RLPK; ribosomal protein S6 kinase, 90kD, polypeptide 5; MSPK1; 90 kDa ribosomal protein S6 kinase 5; R ......
Chromosomal Location	14q31-q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RPS6KA5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RPS6KA5. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	RPS6KA5
Name	ribosomal protein S6 kinase, 90kDa, polypeptide 5
Aliases	MSK1; RLPK; ribosomal protein S6 kinase, 90kD, polypeptide 5; MSPK1; 90 kDa ribosomal protein S6 kinase 5; R ......
Chromosomal Location	14q31-q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RPS6KA5. 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	RPS6KA5
Name	ribosomal protein S6 kinase, 90kDa, polypeptide 5
Aliases	MSK1; RLPK; ribosomal protein S6 kinase, 90kD, polypeptide 5; MSPK1; 90 kDa ribosomal protein S6 kinase 5; R ......
Chromosomal Location	14q31-q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of RPS6KA5 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	RPS6KA5
Name	ribosomal protein S6 kinase, 90kDa, polypeptide 5
Aliases	MSK1; RLPK; ribosomal protein S6 kinase, 90kD, polypeptide 5; MSPK1; 90 kDa ribosomal protein S6 kinase 5; R ......
Chromosomal Location	14q31-q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between RPS6KA5 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	RPS6KA5
Name	ribosomal protein S6 kinase, 90kDa, polypeptide 5
Aliases	MSK1; RLPK; ribosomal protein S6 kinase, 90kD, polypeptide 5; MSPK1; 90 kDa ribosomal protein S6 kinase 5; R ......
Chromosomal Location	14q31-q32.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting RPS6KA5 collected from DrugBank database.

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

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