Dual specificity protein kinase CLK2

Details

Name
Dual specificity protein kinase CLK2
Synonyms
  • 2.7.12.1
  • CDC-like kinase 2
Gene Name
CLK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051728|Dual specificity protein kinase CLK2
MPHPRRYHSSERGSRGSYREHYRSRKHKRRRSRSWSSSSDRTRRRRREDSYHVRSRSSYD
DRSSDRRVYDRRYCGSYRRNDYSRDRGDAYYDTDYRHSYEYQRENSSYRSQRSSRRKHRR
RRRRSRTFSRSSSQHSSRRAKSVEDDAEGHLIYHVGDWLQERYEIVSTLGEGTFGRVVQC
VDHRRGGARVALKIIKNVEKYKEAARLEINVLEKINEKDPDNKNLCVQMFDWFDYHGHMC
ISFELLGLSTFDFLKDNNYLPYPIHQVRHMAFQLCQAVKFLHDNKLTHTDLKPENILFVN
SDYELTYNLEKKRDERSVKSTAVRVVDFGSATFDHEHHSTIVSTRHYRAPEVILELGWSQ
PCDVWSIGCIIFEYYVGFTLFQTHDNREHLAMMERILGPIPSRMIRKTRKQKYFYRGRLD
WDENTSAGRYVRENCKPLRRYLTSEAEEHHQLFDLIESMLEYEPAKRLTLGEALQHPFFA
RLRAEPPNKLWDSSRDISR
Number of residues
499
Molecular Weight
60089.64
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / identical protein binding / protein serine/threonine kinase activity / protein serine/threonine/tyrosine kinase activity / protein tyrosine kinase activity
Processes
negative regulation of gluconeogenesis / protein autophosphorylation / protein phosphorylation / regulation of RNA splicing / response to ionizing radiation / response to retinoic acid
Components
nuclear body / nuclear speck / nucleoplasm / nucleus
General Function
Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Acts as a suppressor of hepatic gluconeogenesis and glucose output by repressing PPARGC1A transcriptional activity on gluconeogenic genes via its phosphorylation. Phosphorylates PPP2R5B thereby stimulating the assembly of PP2A phosphatase with the PPP2R5B-AKT1 complex leading to dephosphorylation of AKT1. Phosphorylates: PTPN1, SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0051729|Dual specificity protein kinase CLK2 (CLK2)
ATGCCGCATCCTCGAAGGTACCACTCCTCAGAGCGAGGCAGCCGGGGGAGTTACCGTGAA
CACTATCGGAGCCGAAAGCATAAGCGACGAAGAAGTCGCTCCTGGTCAAGTAGTAGTGAC
CGGACACGACGGCGTCGGCGAGAGGACAGCTACCATGTCCGTTCTCGAAGCAGTTATGAT
GATCGTTCGTCCGACCGGAGGGTGTATGACCGGCGATACTGTGGCAGCTACAGACGCAAC
GATTATAGCCGGGATCGGGGAGATGCCTACTATGACACAGACTATCGGCATTCCTATGAA
TATCAGCGGGAGAACAGCAGTTACCGCAGCCAGCGCAGCAGCCGGAGGAAGCACAGACGG
CGGAGGAGGCGCAGCCGGACATTTAGCCGCTCATCTTCGCAGCACAGCAGCCGGAGAGCC
AAGAGTGTAGAGGACGACGCTGAGGGCCACCTCATCTACCACGTCGGGGACTGGCTACAA
GAGCGATATGAAATCGTTAGCACCTTAGGAGAGGGGACCTTCGGCCGAGTTGTACAATGT
GTTGACCATCGCAGGGGTGGGGCTCGAGTTGCCCTGAAGATCATTAAGAATGTGGAGAAG
TACAAGGAAGCAGCTCGACTTGAGATCAACGTGCTAGAGAAAATCAATGAGAAAGACCCT
GACAACAAGAACCTCTGTGTCCAGATGTTTGACTGGTTTGACTACCATGGCCACATGTGT
ATCTCCTTTGAGCTTCTGGGCCTTAGCACCTTCGATTTCCTCAAAGACAACAACTACCTG
CCCTACCCCATCCACCAAGTGCGCCACATGGCCTTCCAGCTGTGCCAGGCTGTCAAGTTC
CTCCATGATAACAAGCTGACACATACAGACCTCAAGCCTGAAAATATTCTGTTTGTGAAT
TCAGACTATGAGCTCACCTACAACCTAGAGAAGAAGCGAGATGAGCGCAGTGTGAAGAGC
ACAGCTGTGCGGGTGGTAGACTTTGGCAGTGCCACCTTTGACCATGAGCACCATAGCACC
ATTGTCTCCACTCGCCATTACCGAGCACCAGAAGTCATCCTTGAGTTGGGCTGGTCACAG
CCTTGTGATGTGTGGAGTATAGGCTGCATCATCTTTGAATACTATGTGGGATTCACCCTC
TTCCAGACCCATGACAACAGAGAGCATCTAGCCATGATGGAAAGGATCTTGGGTCCTATC
CCTTCCCGGATGATCCGAAAGACAAGAAAGCAGAAATATTTTTACCGGGGTCGCCTGGAT
TGGGATGAGAACACATCAGCTGGGCGCTATGTTCGTGAGAACTGCAAACCGCTGCGGCGG
TATCTGACCTCAGAGGCAGAGGAACACCACCAGCTCTTCGATCTGATTGAAAGCATGCTA
GAGTATGAACCAGCTAAGCGGCTGACCTTGGGTGAAGCCCTTCAGCATCCTTTCTTCGCC
CGCCTTCGGGCTGAGCCGCCCAACAAGTTGTGGGACTCCAGTCGGGATATCAGTCGGTGA
Chromosome Location
1
Locus
1q22
External Identifiers
ResourceLink
UniProtKB IDP49760
UniProtKB Entry NameCLK2_HUMAN
HGNC IDHGNC:2069
General References
  1. Hanes J, von der Kammer H, Klaudiny J, Scheit KH: Characterization by cDNA cloning of two new human protein kinases. Evidence by sequence comparison of a new family of mammalian protein kinases. J Mol Biol. 1994 Dec 16;244(5):665-72. [Article]
  2. Winfield SL, Tayebi N, Martin BM, Ginns EI, Sidransky E: Identification of three additional genes contiguous to the glucocerebrosidase locus on chromosome 1q21: implications for Gaucher disease. Genome Res. 1997 Oct;7(10):1020-6. [Article]
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  5. Lee K, Du C, Horn M, Rabinow L: Activity and autophosphorylation of LAMMER protein kinases. J Biol Chem. 1996 Nov 1;271(44):27299-303. [Article]
  6. Duncan PI, Stojdl DF, Marius RM, Scheit KH, Bell JC: The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing. Exp Cell Res. 1998 Jun 15;241(2):300-8. [Article]
  7. Moeslein FM, Myers MP, Landreth GE: The CLK family kinases, CLK1 and CLK2, phosphorylate and activate the tyrosine phosphatase, PTP-1B. J Biol Chem. 1999 Sep 17;274(38):26697-704. [Article]
  8. Kantham L, Kerr-Bayles L, Godde N, Quick M, Webb R, Sunderland T, Bond J, Walder K, Augert G, Collier G: Beacon interacts with cdc2/cdc28-like kinases. Biochem Biophys Res Commun. 2003 Apr 25;304(1):125-9. [Article]
  9. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [Article]
  10. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  11. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  12. Eisenreich A, Bogdanov VY, Zakrzewicz A, Pries A, Antoniak S, Poller W, Schultheiss HP, Rauch U: Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. Circ Res. 2009 Mar 13;104(5):589-99. doi: 10.1161/CIRCRESAHA.108.183905. Epub 2009 Jan 22. [Article]
  13. Heinrich B, Zhang Z, Raitskin O, Hiller M, Benderska N, Hartmann AM, Bracco L, Elliott D, Ben-Ari S, Soreq H, Sperling J, Sperling R, Stamm S: Heterogeneous nuclear ribonucleoprotein G regulates splice site selection by binding to CC(A/C)-rich regions in pre-mRNA. J Biol Chem. 2009 May 22;284(21):14303-15. doi: 10.1074/jbc.M901026200. Epub 2009 Mar 12. [Article]
  14. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  15. Nam SY, Seo HH, Park HS, An S, Kim JY, Yang KH, Kim CS, Jeong M, Jin YW: Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell survival after ionizing radiation. J Biol Chem. 2010 Oct 8;285(41):31157-63. doi: 10.1074/jbc.M110.122044. Epub 2010 Aug 3. [Article]
  16. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails