TISIDB

Summary
Symbol	SRPK1
Name	SRSF protein kinase 1
Aliases	SFRSK1; SR protein kinase 1; serine/arginine-rich splicing factor kinase 1; SFRS protein kinase 1; SR-protei ......
Chromosomal Location	6p21.31
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	Isoform 2: Cytoplasm. Nucleus. Nucleus matrix. Microsome. Note=Shuttles between the nucleus and the cytoplasm. Inhibition of the Hsp90 ATPase activity, osmotic stress and interaction with HHV-1 ICP27 protein can induce its translocation to the nucleus. KAT5/TIP60 inhibits its nuclear translocation.; SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Nucleus matrix. Microsome. Note=Mainly localized in the microsomal fraction and the cytoplasm, and to a lesser extent in the nuclear matrix.
Domain	PF00069 Protein kinase domain
Function	Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. Can influence additional steps of mRNA maturation, as well as other cellular activities, such as chromatin reorganization in somatic and sperm cells and cell cycle progression. Isoform 2 phosphorylates SFRS2, ZRSR2, LBR and PRM1. Isoform 2 phosphorylates SRSF1 using a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds first to a docking groove in the large lobe of the kinase domain of SRPK1. This induces certain structural changes in SRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM2, which then docks at the docking groove of SRPK1. This also signals RRM2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. Isoform 2 can mediate hepatitis B virus (HBV) core protein phosphorylation. It plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Isoform 1 and isoform 2 can induce splicing of exon 10 in MAPT/TAU. The ratio of isoform 1/isoform 2 plays a decisive role in determining cell fate in K-562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation.

> Gene Ontology [ TOP ]
Biological Process	GO:0000375 RNA splicing, via transesterification reactions GO:0000377 RNA splicing, via transesterification reactions with bulged adenosine as nucleophile GO:0000398 mRNA splicing, via spliceosome GO:0006323 DNA packaging GO:0006397 mRNA processing GO:0006997 nucleus organization GO:0007059 chromosome segregation GO:0007281 germ cell development GO:0007283 spermatogenesis GO:0007286 spermatid development GO:0007289 spermatid nucleus differentiation GO:0008380 RNA splicing GO:0019058 viral life cycle GO:0019079 viral genome replication GO:0022412 cellular process involved in reproduction in multicellular organism GO:0035092 sperm chromatin condensation GO:0043484 regulation of RNA splicing GO:0043900 regulation of multi-organism process GO:0043901 negative regulation of multi-organism process GO:0043902 positive regulation of multi-organism process GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism GO:0045069 regulation of viral genome replication GO:0045070 positive regulation of viral genome replication GO:0045071 negative regulation of viral genome replication GO:0048024 regulation of mRNA splicing, via spliceosome GO:0048232 male gamete generation GO:0048515 spermatid differentiation GO:0048524 positive regulation of viral process GO:0048525 negative regulation of viral process GO:0050684 regulation of mRNA processing GO:0050792 regulation of viral process GO:0071103 DNA conformation change GO:1903311 regulation of mRNA metabolic process GO:1903900 regulation of viral life cycle GO:1903901 negative regulation of viral life cycle GO:1903902 positive regulation of viral life cycle
Molecular Function	GO:0000287 magnesium ion binding GO:0004674 protein serine/threonine kinase activity
Cellular Component	GO:0016363 nuclear matrix GO:0034399 nuclear periphery

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	SRPK1
Name	SRSF protein kinase 1
Aliases	SFRSK1; SR protein kinase 1; serine/arginine-rich splicing factor kinase 1; SFRS protein kinase 1; SR-protei ......
Chromosomal Location	6p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between SRPK1 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	SRPK1
Name	SRSF protein kinase 1
Aliases	SFRSK1; SR protein kinase 1; serine/arginine-rich splicing factor kinase 1; SFRS protein kinase 1; SR-protei ......
Chromosomal Location	6p21.31
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 SRPK1 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: 3.74; FDR: 0.046	Sensitive to T cell-mediated killing
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	SRPK1
Name	SRSF protein kinase 1
Aliases	SFRSK1; SR protein kinase 1; serine/arginine-rich splicing factor kinase 1; SFRS protein kinase 1; SR-protei ......
Chromosomal Location	6p21.31
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 SRPK1 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	0.2	0.513
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.208	0.903
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.19	0.886
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.356	0.244
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.295	0.885
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.433	0.868
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.019	0.961
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.003	0.999
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.086	0.964
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.201	0.863
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	0.339	0.836
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.167	0.0307

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of SRPK1 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	21.4	0	21.4	0.081
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	30	0	30	0.528
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	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	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	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	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	SRPK1
Name	SRSF protein kinase 1
Aliases	SFRSK1; SR protein kinase 1; serine/arginine-rich splicing factor kinase 1; SFRS protein kinase 1; SR-protei ......
Chromosomal Location	6p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SRPK1. 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	SRPK1
Name	SRSF protein kinase 1
Aliases	SFRSK1; SR protein kinase 1; serine/arginine-rich splicing factor kinase 1; SFRS protein kinase 1; SR-protei ......
Chromosomal Location	6p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SRPK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SRPK1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	SRPK1
Name	SRSF protein kinase 1
Aliases	SFRSK1; SR protein kinase 1; serine/arginine-rich splicing factor kinase 1; SFRS protein kinase 1; SR-protei ......
Chromosomal Location	6p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SRPK1. 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	SRPK1
Name	SRSF protein kinase 1
Aliases	SFRSK1; SR protein kinase 1; serine/arginine-rich splicing factor kinase 1; SFRS protein kinase 1; SR-protei ......
Chromosomal Location	6p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of SRPK1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	SRPK1
Name	SRSF protein kinase 1
Aliases	SFRSK1; SR protein kinase 1; serine/arginine-rich splicing factor kinase 1; SFRS protein kinase 1; SR-protei ......
Chromosomal Location	6p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between SRPK1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	SRPK1
Name	SRSF protein kinase 1
Aliases	SFRSK1; SR protein kinase 1; serine/arginine-rich splicing factor kinase 1; SFRS protein kinase 1; SR-protei ......
Chromosomal Location	6p21.31
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting SRPK1 collected from DrugBank database.

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

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