SRPK1

SRPK1
Identifiers
Aliases	SRPK1, SFRSK1, SRSF protein kinase 1
External IDs	OMIM: 601939; MGI: 106908; GeneCards: SRPK1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1WAK, 1WBP, 3BEG, 4WUA
Enzyme activity
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	28,841,683 bp
RNA expression pattern
	Top expressed in
	sperm; ; trabecular bone; ; bone marrow; ; secondary oocyte; ; endothelial cell; ; blood; ; bone marrow cell; ; human penis; ; rectum; ; thymus;
	Top expressed in
	tail of embryo; ; genital tubercle; ; morula; ; secondary oocyte; ; spermatid; ; zygote; ; spermatocyte; ; primary oocyte; ; primitive streak; ; seminiferous tubule;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	transferase activity; protein kinase activity; nucleotide binding; kinase activity; protein serine/threonine kinase activity; protein binding; ATP binding; magnesium ion binding; RNA binding;
Cellular component	cytoplasm; intracellular membrane-bounded organelle; nuclear matrix; plasma membrane; endoplasmic reticulum; nucleus; cytosol;
Biological process	cell differentiation; intracellular signal transduction; phosphorylation; regulation of mRNA processing; chromosome segregation; mRNA processing; regulation of mRNA splicing, via spliceosome; protein phosphorylation; negative regulation of viral genome replication; RNA splicing; positive regulation of viral genome replication; innate immune response; viral process; sperm DNA condensation; spliceosomal complex assembly; regulation of gene expression;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry
	6732
	20815
	n/a
	ENSMUSG00000004865
	Q96SB4
	O70551
	NM_003137
	NM_016795
	NP_003128
	NP_058075
	Wikidata
View/Edit Human	View/Edit Mouse

Serine/arginine-Rich Splicing Factor (SRSF) protein kinase-1 SRPK1 is an enzyme that in humans is encoded by the SRPK1 gene.

Function

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. A second alternatively spliced transcript variant for this gene has been described, but its full length nature has not been determined.

SRPK1 enables angiogenesis, which is regulated by VEGF, which either initiates or inhibits vessel formation depending on alternative splicing.

Medical applications

Some cancers are vascular endothelial growth factor (VEGF) dependant (for angiogenesis). SRPK1 activates (phosphorylates) VEGF splicing factor. SRPK1 inhibitors (e.g. 'SPHINX compounds' ) are under investigation as treatments for prostate cancer, acute myeloid leukemia and neovascular eye disease.

Interactions

SRPK1 has been shown to interact with:

References

1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000004865 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Gui JF, Lane WS, Fu XD (July 1994). "A serine kinase regulates intracellular localization of splicing factors in the cell cycle". Nature. 369 (6482): 678–682. Bibcode:1994Natur.369..678G. doi:10.1038/369678a0. PMID 8208298. S2CID 4275539. Archived from the original on 2020-12-03. Retrieved 2019-01-07.
↑ Wang HY, Arden KC, Bermingham JR, Viars CS, Lin W, Boyer AD, et al. (May 1999). "Localization of serine kinases, SRPK1 (SFRSK1) and SRPK2 (SFRSK2), specific for the SR family of splicing factors in mouse and human chromosomes". Genomics. 57 (2): 310–315. doi:10.1006/geno.1999.5770. PMID 10198174.
1 2 "Entrez Gene: SRPK1 SFRS protein kinase 1".
↑ "Development of novel anti-angiogenic SRPK1 inhibitors" (PDF).
↑ "Molecular breakthrough could halt spread of prostate cancer". ScienceDaily.
↑ Mavrou A, Brakspear K, Hamdollah-Zadeh M, Damodaran G, Babaei-Jadidi R, Oxley J, et al. (2014). "Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer". Oncogene. 34 (33): 4311–4319. doi:10.1038/onc.2014.360. PMC 4351909. PMID 25381816.
↑ Batson J, Toop HD, Redondo C, Babaei-Jadidi R, Chaikuad A, Wearmouth SF, et al. (March 2017). "Development of Potent, Selective SRPK1 Inhibitors as Potential Topical Therapeutics for Neovascular Eye Disease". ACS Chemical Biology. 12 (3): 825–832. doi:10.1021/acschembio.6b01048. hdl:1983/805bd6f0-5220-4592-a3d2-9a58543c0bd9. PMID 28135068.
↑ Tzelepis K, De Braekeleer E, Aspris D, Barbieri I, Vijayabaskar MS, Liu WH, et al. (December 2018). "SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4". Nature Communications. 9 (1) 5378. Bibcode:2018NatCo...9.5378T. doi:10.1038/s41467-018-07620-0. PMC 6300607. PMID 30568163.
1 2 Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, et al. (February 1998). "SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells". The Journal of Cell Biology. 140 (4): 737–750. doi:10.1083/jcb.140.4.737. PMC 2141757. PMID 9472028.
↑ Lukasiewicz R, Velazquez-Dones A, Huynh N, Hagopian J, Fu XD, Adams J, et al. (August 2007). "Structurally unique yeast and mammalian serine-arginine protein kinases catalyze evolutionarily conserved phosphorylation reactions". The Journal of Biological Chemistry. 282 (32): 23036–23043. doi:10.1074/jbc.M611305200. PMID 17517895.
↑ Umehara H, Nishii Y, Morishima M, Kakehi Y, Kioka N, Amachi T, et al. (February 2003). "Effect of cisplatin treatment on speckled distribution of a serine/arginine-rich nuclear protein CROP/Luc7A". Biochemical and Biophysical Research Communications. 301 (2): 324–329. doi:10.1016/s0006-291x(02)03017-6. PMID 12565863.
↑ Koizumi J, Okamoto Y, Onogi H, Mayeda A, Krainer AR, Hagiwara M (April 1999). "The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs)". The Journal of Biological Chemistry. 274 (16): 11125–11131. doi:10.1074/jbc.274.16.11125. PMID 10196197.
↑ Kamachi M, Le TM, Kim SJ, Geiger ME, Anderson P, Utz PJ (November 2002). "Human autoimmune sera as molecular probes for the identification of an autoantigen kinase signaling pathway". The Journal of Experimental Medicine. 196 (9): 1213–1225. doi:10.1084/jem.20021167. PMC 2194102. PMID 12417631.
↑ Varjosalo M, Keskitalo S, Van Drogen A, Nurkkala H, Vichalkovski A, Aebersold R, et al. (April 2013). "The protein interaction landscape of the human CMGC kinase group". Cell Reports. 3 (4): 1306–1320. doi:10.1016/j.celrep.2013.03.027. hdl:20.500.11850/70524. PMID 23602568.

Colwill K, Feng LL, Yeakley JM, Gish GD, Cáceres JF, Pawson T, et al. (1996). "SRPK1 and Clk/Sty protein kinases show distinct substrate specificities for serine/arginine-rich splicing factors". The Journal of Biological Chemistry. 271 (40): 24569–24575. doi:10.1074/jbc.271.40.24569. PMID 8798720.
Papoutsopoulou S, Nikolakaki E, Giannakouros T (1999). "SRPK1 and LBR protein kinases show identical substrate specificities". Biochemical and Biophysical Research Communications. 255 (3): 602–607. doi:10.1006/bbrc.1999.0249. PMID 10049757.
Paillard F (1999). "A novel soluble chimera for the treatment of familial hypercholesterolemia". Human Gene Therapy. 10 (7): 1093–1094. doi:10.1089/10430349950018085. PMID 10340541.
Papoutsopoulou S, Nikolakaki E, Chalepakis G, Kruft V, Chevaillier P, Giannakouros T (1999). "SR protein-specific kinase 1 is highly expressed in testis and phosphorylates protamine 1". Nucleic Acids Research. 27 (14): 2972–2980. doi:10.1093/nar/27.14.2972. PMC 148514. PMID 10390541.
Nikolakaki E, Kohen R, Hartmann AM, Stamm S, Georgatsou E, Giannakouros T (2001). "Cloning and characterization of an alternatively spliced form of SR protein kinase 1 that interacts specifically with scaffold attachment factor-B". The Journal of Biological Chemistry. 276 (43): 40175–40182. doi:10.1074/jbc.M104755200. PMID 11509566.
Daub H, Blencke S, Habenberger P, Kurtenbach A, Dennenmoser J, Wissing J, et al. (2002). "Identification of SRPK1 and SRPK2 as the Major Cellular Protein Kinases Phosphorylating Hepatitis B Virus Core Protein". Journal of Virology. 76 (16): 8124–8137. doi:10.1128/JVI.76.16.8124-8137.2002. PMC 155132. PMID 12134018.
Mylonis I, Giannakouros T (2003). "Protein kinase CK2 phosphorylates and activates the SR protein-specific kinase 1". Biochemical and Biophysical Research Communications. 301 (3): 650–656. doi:10.1016/S0006-291X(02)03055-3. PMID 12565829.
Aubol BE, Chakrabarti S, Ngo J, Shaffer J, Nolen B, Fu XD, et al. (2004). "Processive phosphorylation of alternative splicing factor/splicing factor 2". Proceedings of the National Academy of Sciences of the United States of America. 100 (22): 12601–12606. Bibcode:2003PNAS..10012601A. doi:10.1073/pnas.1635129100. PMC 240664. PMID 14555757.
Li J, Hawkins IC, Harvey CD, Jennings JL, Link AJ, Patton JG (2003). "Regulation of Alternative Splicing by SRrp86 and Its Interacting Proteins". Molecular and Cellular Biology. 23 (21): 7437–7447. doi:10.1128/MCB.23.21.7437-7447.2003. PMC 207616. PMID 14559993.
Mylonis I, Drosou V, Brancorsini S, Nikolakaki E, Sassone-Corsi P, Giannakouros T (2004). "Temporal association of protamine 1 with the inner nuclear membrane protein lamin B receptor during spermiogenesis". The Journal of Biological Chemistry. 279 (12): 11626–11631. doi:10.1074/jbc.M311949200. PMID 14701833.
Lee CG, Hague LK, Li H, Donnelly R (2004). "Identification of toposome, a novel multisubunit complex containing topoisomerase IIalpha". Cell Cycle. 3 (5). Georgetown, Tex.: 638–647. doi:10.4161/cc.3.5.825. PMID 15034300.
Jin J, Smith FD, Stark C, Wells CD, Fawcett JP, Kulkarni S, et al. (2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Current Biology. 14 (16): 1436–1450. Bibcode:2004CBio...14.1436J. doi:10.1016/j.cub.2004.07.051. PMID 15324660. S2CID 2371325.

[refGRCm38Ensembl-1] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000004865 – Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Gui_1994-4] Gui JF, Lane WS, Fu XD (July 1994). "A serine kinase regulates intracellular localization of splicing factors in the cell cycle". Nature. 369 (6482): 678–682. Bibcode:1994Natur.369..678G. doi:10.1038/369678a0. PMID 8208298. S2CID 4275539. Archived from the original on 2020-12-03. Retrieved 2019-01-07.

[Wang_1999-5] Wang HY, Arden KC, Bermingham JR, Viars CS, Lin W, Boyer AD, et al. (May 1999). "Localization of serine kinases, SRPK1 (SFRSK1) and SRPK2 (SFRSK2), specific for the SR family of splicing factors in mouse and human chromosomes". Genomics. 57 (2): 310–315. doi:10.1006/geno.1999.5770. PMID 10198174.

[entrez-6] 1 2 "Entrez Gene: SRPK1 SFRS protein kinase 1".

[7] "Development of novel anti-angiogenic SRPK1 inhibitors" (PDF).

[8] "Molecular breakthrough could halt spread of prostate cancer". ScienceDaily.

[Mavrou2014-9] Mavrou A, Brakspear K, Hamdollah-Zadeh M, Damodaran G, Babaei-Jadidi R, Oxley J, et al. (2014). "Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer". Oncogene. 34 (33): 4311–4319. doi:10.1038/onc.2014.360. PMC 4351909. PMID 25381816.

[10] Batson J, Toop HD, Redondo C, Babaei-Jadidi R, Chaikuad A, Wearmouth SF, et al. (March 2017). "Development of Potent, Selective SRPK1 Inhibitors as Potential Topical Therapeutics for Neovascular Eye Disease". ACS Chemical Biology. 12 (3): 825–832. doi:10.1021/acschembio.6b01048. hdl:1983/805bd6f0-5220-4592-a3d2-9a58543c0bd9. PMID 28135068.

[11] Tzelepis K, De Braekeleer E, Aspris D, Barbieri I, Vijayabaskar MS, Liu WH, et al. (December 2018). "SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4". Nature Communications. 9 (1) 5378. Bibcode:2018NatCo...9.5378T. doi:10.1038/s41467-018-07620-0. PMC 6300607. PMID 30568163.

[Wang_1998-12] 1 2 Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, et al. (February 1998). "SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells". The Journal of Cell Biology. 140 (4): 737–750. doi:10.1083/jcb.140.4.737. PMC 2141757. PMID 9472028.

[Lukasiewicz_2007-13] Lukasiewicz R, Velazquez-Dones A, Huynh N, Hagopian J, Fu XD, Adams J, et al. (August 2007). "Structurally unique yeast and mammalian serine-arginine protein kinases catalyze evolutionarily conserved phosphorylation reactions". The Journal of Biological Chemistry. 282 (32): 23036–23043. doi:10.1074/jbc.M611305200. PMID 17517895.

[Umehara_2003-14] Umehara H, Nishii Y, Morishima M, Kakehi Y, Kioka N, Amachi T, et al. (February 2003). "Effect of cisplatin treatment on speckled distribution of a serine/arginine-rich nuclear protein CROP/Luc7A". Biochemical and Biophysical Research Communications. 301 (2): 324–329. doi:10.1016/s0006-291x(02)03017-6. PMID 12565863.

[Koizumi_1999-15] Koizumi J, Okamoto Y, Onogi H, Mayeda A, Krainer AR, Hagiwara M (April 1999). "The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs)". The Journal of Biological Chemistry. 274 (16): 11125–11131. doi:10.1074/jbc.274.16.11125. PMID 10196197.

[Kamachi_2002-16] Kamachi M, Le TM, Kim SJ, Geiger ME, Anderson P, Utz PJ (November 2002). "Human autoimmune sera as molecular probes for the identification of an autoantigen kinase signaling pathway". The Journal of Experimental Medicine. 196 (9): 1213–1225. doi:10.1084/jem.20021167. PMC 2194102. PMID 12417631.

[17] Varjosalo M, Keskitalo S, Van Drogen A, Nurkkala H, Vichalkovski A, Aebersold R, et al. (April 2013). "The protein interaction landscape of the human CMGC kinase group". Cell Reports. 3 (4): 1306–1320. doi:10.1016/j.celrep.2013.03.027. hdl:20.500.11850/70524. PMID 23602568.

SRPK1

Function

Medical applications

Interactions

References

Further reading