SRPK1

SRPK1
Identifiers
AliasesSRPK1, SFRSK1, SRSF protein kinase 1
External IDsOMIM: 601939; MGI: 106908; GeneCards: SRPK1
Available structures
PDBOrtholog search: PDBe RCSB
Enzyme activity
EC #BRENDAExPASyKEGGMetaCyc
2.7.11.1↗↗↗↗
Orthologs
DatabasesNCBI: entry
SpeciesHumanMouse
Entrez

6732

20815

Ensembl

n/a

ENSMUSG00000004865

UniProt

Q96SB4

O70551

RefSeq (mRNA)

NM_003137

NM_016795

RefSeq (protein)

NP_003128

NP_058075

Location (UCSC)n/aChr 17: 28.81 – 28.84 Mb
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

Serine/arginine-Rich Splicing Factor (SRSF) protein kinase-1 SRPK1 is an enzyme that in humans is encoded by the SRPK1 gene.[4][5][6]

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.[6]

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' [7]) are under investigation as treatments for prostate cancer, acute myeloid leukemia and neovascular eye disease.[8][9][10][11]

Interactions

SRPK1 has been shown to interact with:

References

  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.
  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.

Further reading

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