Tchem SRPK1 SRSF protein kinase 1

Protein Summary

Description

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. This gene encodes a serine/arginine protein kinase specific for the SR (serine/arginine-rich domain) family of splicing factors. The protein localizes to the nucleus and the cytoplasm. It is thought to play a role in regulation of both constitutive and alternative splicing by regulating intracellular localization of splicing factors. Alternative splicing of this gene results in multiple transcript variants. Additional alternatively spliced transcript variants have been described for this gene, but their full length nature have not been determined.[provided by RefSeq, Jul 2010]

Uniprot Accession IDs

• Q96SB4
• B4DS61
• Q12890
• Q5R364
• Q5R365
• Q8IY12

Gene Name

• SRPK1

Ensembl ID

• ENST00000373825
• ENSP00000362931
• ENSG00000096063
• ENST00000423325
• ENSP00000391069

Symbol

• SFRSK1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.97
kinase perturbation	0.95
disease perturbation	0.93
virus perturbation	0.85
transcription factor perturbation	0.84

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Srsf Protein Kinase 1

DTO Classes

Protein / Kinase / Protein Kinase / Cmgc Group / Srpk Family / Srsf Protein Kinase 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 123.41   (req: < 5)

Gene RIFs: 54   (req: <= 3)

Antibodies: 422   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 123.41   (req: >= 5)

Gene RIFs: 54   (req: > 3)

Antibodies: 422   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 4

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (5)

ProKinO

The ProKinO is a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on kinases.

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (4)

Explore Active Ligands

1 – 4 of 4

staurosporine

SRPK1Tchem Kinase

pKd : 7.89

lestaurtinib

SRPK1Tchem Kinase

pKd : 7.57

SID103905618

SRPK1Tchem Kinase

pKi : 7.6

compound 13 [PMID: 15925511]

SRPK1Tchem Kinase

pIC50 : 7.4

Protein-Protein Interactions (127)

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1 – 10 of 127

• See Interactions on String-DB

RBM27

Tdark

Novelty:  0.04875536

p_int:  0.999602517

p_ni:  0.000397482

p_wrong:  1e-9

Score:  0.444

Data Source:  BioPlex,STRINGDB

U2AF2

Tbio

Novelty:  0.00590935

p_int:  0.999531098

p_ni:  0.000468902

Score:  0.871

Data Source:  BioPlex,STRINGDB

U2AF1

Tbio

Novelty:  0.01181981

p_int:  0.999138306

p_ni:  0.000861694

Score:  0.677

Data Source:  BioPlex,STRINGDB

DROSHA

Tbio

Family:  Enzyme

Novelty:  0.00107123

p_int:  0.995696048

p_ni:  0.004303952

Score:  0.826

Data Source:  BioPlex,STRINGDB

LUC7L

Tbio

Novelty:  0.05748021

p_int:  0.994128586

p_ni:  0.005871414

Score:  0.703

Data Source:  BioPlex,STRINGDB

DHX8

Tbio

Family:  Enzyme

Novelty:  0.01584745

p_int:  0.993422473

p_ni:  0.006577527

Score:  0.243

Data Source:  BioPlex,STRINGDB

ACIN1

Tbio

Novelty:  0.01675479

p_int:  0.993414357

p_ni:  0.006585643

Score:  0.734

Data Source:  BioPlex,STRINGDB

HDGFL2

Tbio

Family:  Epigenetic

Novelty:  0.11846257

p_int:  0.981127986

p_ni:  0.018872013

Data Source:  BioPlex

ZRSR2

Tbio

Novelty:  0.03449891

p_int:  0.974167449

p_ni:  0.025832551

Score:  0.246

Data Source:  BioPlex,STRINGDB

RBMX2

Tbio

Novelty:  0.08867468

p_int:  0.911907614

p_ni:  0.088092366

p_wrong:  2.1e-8

Score:  0.161

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (2)

KEGG (1)

WikiPathways (1)

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5

1 – 1 of 1

Data Source	Name	Explore in Pharos	Explore in Source
KEGG	Herpes simplex virus 1 infection	567 targets	path:hsa05168

Name	Explore in Pharos	Explore in Source
Herpes simplex virus 1 infection	567 targets	path:hsa05168

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (24)

Functions (5)

Components (6)

Processes (13)

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1 – 5 of 5

GO Term	Evidence	Assigned by
ATP binding	Inferred from Direct Assay (IDA)	UniProtKB
magnesium ion binding	Inferred from Direct Assay (IDA)	UniProtKB
protein serine/threonine kinase activity	Inferred from Direct Assay (IDA)	UniProtKB
RNA binding	Inferred from High Throughput Direct Assay (HDA)	UniProtKB
protein kinase activity	Traceable Author Statement (TAS)	ProtInc

Disease Associations (null)

No disease associations found

GWAS Traits (10)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 10

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
reticulocyte measurement	EFO_0010700	2	1	2		68.8
mean reticulocyte volume	EFO_0010701	1	1	1		63.4
eosinophil count	EFO_0004842	1	1	1		60.2
waist-hip ratio	EFO_0004343	1	1	1		45.7
reticulocyte count	EFO_0007986	1	1	1		44.2

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 10

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
reticulocyte measurement	EFO_0010700	2		68.8
mean reticulocyte volume	EFO_0010701	1		63.4
eosinophil count	EFO_0004842	1		60.2
waist-hip ratio	EFO_0004343	1		45.7
reticulocyte count	EFO_0007986	1		44.2

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
ATP-binding
Chromosome partition
Complete proteome
Cytoplasm
Differentiation
Direct protein sequencing
Endoplasmic reticulum
Host-virus interaction

GWAS Trait Find Similar Targets

No Header	No Header
BMI-adjusted hip circumference
BMI-adjusted waist-hip ratio
eosinophil count
eosinophil percentage of granulocytes
eosinophil percentage of leukocytes
mean corpuscular volume
mean reticulocyte volume
reticulocyte count
reticulocyte measurement
waist-hip ratio

IDG Resources

No IDG generated resources found

Orthologs (13)

1 – 5 of 13

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	SRSF protein kinase 1	VGNC:3711	462640
Macaque	SRSF protein kinase 1		719039
Mouse	serine/arginine-rich protein specific kinase 1	MGI:106908	20815
Rat	SRSF protein kinase 1	RGD:1308272	361811
Dog	SRSF protein kinase 1	VGNC:54365	474887

Species	Name	OMA	EggNOG	Inparanoid
Chimp	SRSF protein kinase 1
Macaque	SRSF protein kinase 1
Mouse	serine/arginine-rich protein specific kinase 1
Rat	SRSF protein kinase 1
Dog	SRSF protein kinase 1

Publication Statistics

PubMed Score 123.41

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PubTator Score 84.89

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Related Publications

Text Mined References (86)

GeneRif Annotations (54)

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PMID	Year	Title