SRPK1

Serine/threonine-protein kinase SRPK1 is an enzyme that in humans is encoded by the SRPK1 gene.[5][6][7]

SRPK1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSRPK1, SFRSK1, SRSF protein kinase 1
External IDsOMIM: 601939 MGI: 106908 HomoloGene: 110962 GeneCards: SRPK1
Gene location (Human)
Chr.Chromosome 6 (human)[1]
Band6p21.31Start35,832,966 bp[1]
End35,921,342 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

6732

20815

Ensembl

ENSG00000096063

ENSMUSG00000004865

UniProt

Q96SB4

O70551

RefSeq (mRNA)

NM_003137

NM_016795

RefSeq (protein)

NP_003128

NP_058075

Location (UCSC)Chr 6: 35.83 – 35.92 MbChr 17: 28.59 – 28.62 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[7]

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' [8]) are under investigation as treatments for prostate cancer, acute myeloid leukemia and neovascular eye disease.[9][10][11][12]

Interactions

SRPK1 has been shown to interact with:

References

  1. GRCh38: Ensembl release 89: ENSG00000096063 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000004865 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Gui JF, Lane WS, Fu XD (Jul 1994). "A serine kinase regulates intracellular localization of splicing factors in the cell cycle". Nature. 369 (6482): 678–82. Bibcode:1994Natur.369..678G. doi:10.1038/369678a0. PMID 8208298. S2CID 4275539.
  6. Wang HY, Arden KC, Bermingham JR, Viars CS, Lin W, Boyer AD, Fu XD (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): 310–5. doi:10.1006/geno.1999.5770. PMID 10198174.
  7. "Entrez Gene: SRPK1 SFRS protein kinase 1".
  8. "Development of novel anti-angiogenic SRPK1 inhibitors" (PDF).
  9. "Molecular breakthrough could halt spread of prostate cancer". ScienceDaily.
  10. Mavrou A, Brakspear K, Hamdollah-Zadeh M, Damodaran G, Babaei-Jadidi R, Oxley J, Gillatt DA, Ladomery MR, Harper SJ, Bates DO, Oltean S (2014). "Serine-arginine protein kinase 1 (SRPK1) inhibition as a potential novel targeted therapeutic strategy in prostate cancer". Oncogene. 34 (33): 4311–9. doi:10.1038/onc.2014.360. PMC 4351909. PMID 25381816.
  11. Batson, Jennifer; Toop, Hamish D.; Redondo, Clara; Babaei-Jadidi, Roya; Chaikuad, Apirat; Wearmouth, Stephen F.; Gibbons, Brian; Allen, Claire; Tallant, Cynthia (March 17, 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. ISSN 1554-8937. PMID 28135068.
  12. Vassiliou, George S.; Kouzarides, Tony; Yusa, Kosuke; Bates, David O.; Jeremias, Irmela; Bradley, Allan; Pina, Cristina; Morris, Jonathan C.; Batson, Jennifer (2018-12-19). "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. ISSN 2041-1723. PMC 6300607. PMID 30568163.
  13. Wang HY, Lin W, Dyck JA, Yeakley JM, Songyang Z, Cantley LC, Fu XD (Feb 1998). "SRPK2: a differentially expressed SR protein-specific kinase involved in mediating the interaction and localization of pre-mRNA splicing factors in mammalian cells". J. Cell Biol. 140 (4): 737–50. doi:10.1083/jcb.140.4.737. PMC 2141757. PMID 9472028.
  14. Lukasiewicz R, Velazquez-Dones A, Huynh N, Hagopian J, Fu XD, Adams J, Ghosh G (Aug 2007). "Structurally unique yeast and mammalian serine-arginine protein kinases catalyze evolutionarily conserved phosphorylation reactions". J. Biol. Chem. 282 (32): 23036–43. doi:10.1074/jbc.M611305200. PMID 17517895.
  15. Umehara H, Nishii Y, Morishima M, Kakehi Y, Kioka N, Amachi T, Koizumi J, Hagiwara M, Ueda K (Feb 2003). "Effect of cisplatin treatment on speckled distribution of a serine/arginine-rich nuclear protein CROP/Luc7A". Biochem. Biophys. Res. Commun. 301 (2): 324–9. doi:10.1016/s0006-291x(02)03017-6. PMID 12565863.
  16. Koizumi J, Okamoto Y, Onogi H, Mayeda A, Krainer AR, Hagiwara M (Apr 1999). "The subcellular localization of SF2/ASF is regulated by direct interaction with SR protein kinases (SRPKs)". J. Biol. Chem. 274 (16): 11125–31. doi:10.1074/jbc.274.16.11125. PMID 10196197.
  17. Kamachi M, Le TM, Kim SJ, Geiger ME, Anderson P, Utz PJ (Nov 2002). "Human autoimmune sera as molecular probes for the identification of an autoantigen kinase signaling pathway". J. Exp. Med. 196 (9): 1213–25. doi:10.1084/jem.20021167. PMC 2194102. PMID 12417631.
  18. Varjosalo, Markku; Keskitalo, Salla; Van Drogen, Audrey; Nurkkala, Helka; Vichalkovski, Anton; Aebersold, Ruedi; Gstaiger, Matthias (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. PMID 23602568.

Further reading

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