InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SRPK1

Summary

InnateDB Protein

IDBP-84418.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SRPK1

Protein Name

SRSF protein kinase 1

Synonyms

SFRSK1;

Species

Homo sapiens

Ensembl Protein

ENSP00000362931

InnateDB Gene

IDBG-84414 (SRPK1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10049757, ECO:0000269PubMed:10390541, ECO:0000269PubMed:11509566, ECO:0000269PubMed:12134018, ECO:0000269PubMed:14555757, ECO:0000269PubMed:15034300, ECO:0000269PubMed:16122776, ECO:0000269PubMed:16209947, ECO:0000269PubMed:18155240, ECO:0000269PubMed:18687337, ECO:0000269PubMed:19240134, ECO:0000269PubMed:19477182, ECO:0000269PubMed:19886675, ECO:0000269PubMed:20708644, ECO:0000269PubMed:8208298, ECO:0000269PubMed:9237760}.

Subcellular Localization

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.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.

Disease Associations

Tissue Specificity

Isoform 2 is predominantly expressed in the testis but is also present at lower levels in heart, ovary, small intestine, liver, kidney, pancreas and skeletal muscle. Isoform 1 is only seen in the testis, at lower levels than isoform 2. Highly expressed in different erythroid and lymphoid cell lines, with isoform 2 being far more abundant than isoform 1. {ECO:0000269PubMed:10390541, ECO:0000269PubMed:11509566, ECO:0000269PubMed:20708644}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 372 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	372 [view]
Protein-Protein	372 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0044822	poly(A) RNA binding

Biological Process

GO:0006397	mRNA processing
GO:0006468	protein phosphorylation
GO:0007059	chromosome segregation
GO:0008380	RNA splicing
GO:0016032	viral process
GO:0035092	sperm chromatin condensation
GO:0035556	intracellular signal transduction
GO:0045070	positive regulation of viral genome replication
GO:0045071	negative regulation of viral genome replication
GO:0045087	innate immune response
GO:0048024	regulation of mRNA splicing, via spliceosome
GO:0050684	regulation of mRNA processing

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005783	endoplasmic reticulum
GO:0005886	plasma membrane
GO:0016363	nuclear matrix

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt