Dual specificity protein kinase CLK3

Details

Name

Dual specificity protein kinase CLK3

Synonyms

• 2.7.12.1
• CDC-like kinase 3

Gene Name

CLK3

Organism

Humans

Amino acid sequence

>lcl|BSEQ0007727|Dual specificity protein kinase CLK3
MPVLSARRRELADHAGSGRRSGPSPTARSGPHLSALRAQPARAAHLSGRGTYVRRDTAGG
GPGQARPLGPPGTSLLGRGARRSGEGWCPGAFESGARAARPPSRVEPRLATAASREGAGL
PRAEVAAGSGRGARSGEWGLAAAGAWETMHHCKRYRSPEPDPYLSYRWKRRRSYSREHEG
RLRYPSRREPPPRRSRSRSHDRLPYQRRYRERRDSDTYRCEERSPSFGEDYYGPSRSRHR
RRSRERGPYRTRKHAHHCHKRRTRSCSSASSRSQQSSKRSSRSVEDDKEGHLVCRIGDWL
QERYEIVGNLGEGTFGKVVECLDHARGKSQVALKIIRNVGKYREAARLEINVLKKIKEKD
KENKFLCVLMSDWFNFHGHMCIAFELLGKNTFEFLKENNFQPYPLPHVRHMAYQLCHALR
FLHENQLTHTDLKPENILFVNSEFETLYNEHKSCEEKSVKNTSIRVADFGSATFDHEHHT
TIVATRHYRPPEVILELGWAQPCDVWSIGCILFEYYRGFTLFQTHENREHLVMMEKILGP
IPSHMIHRTRKQKYFYKGGLVWDENSSDGRYVKENCKPLKSYMLQDSLEHVQLFDLMRRM
LEFDPAQRITLAEALLHPFFAGLTPEERSFHTSRNPSR

Number of residues

638

Molecular Weight

73514.365

Theoretical pI

10.37

GO Classification

Functions

ATP binding / poly(A) RNA binding / protein serine/threonine kinase activity / protein serine/threonine/tyrosine kinase activity / protein tyrosine kinase activity

Processes

protein autophosphorylation / protein phosphorylation / regulation of RNA splicing

Components

acrosomal vesicle / intermediate filament cytoskeleton / membrane / nuclear speck / nucleoplasm / nucleus

General Function

Protein tyrosine kinase activity

Specific 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. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.

Pfam Domain Function

• Pkinase (PF00069)

Transmembrane Regions

Not Available

Cellular Location

Nucleus

Gene sequence

>lcl|BSEQ0012814|Dual specificity protein kinase CLK3 (CLK3)
ATGCCCGTCCTCTCCGCGCGCAGGAGGGAGTTGGCGGACCACGCGGGGTCGGGGCGACGG
AGCGGGCCCAGCCCCACGGCCAGGTCGGGGCCCCACCTCTCGGCTCTGAGAGCCCAGCCG
GCCCGGGCCGCGCACCTGTCAGGTCGGGGGACCTACGTGCGCCGCGACACGGCGGGAGGC
GGGCCGGGCCAGGCTCGTCCCCTCGGCCCTCCCGGAACTAGTCTCCTAGGCCGCGGCGCC
CGCCGGAGCGGAGAGGGCTGGTGCCCCGGAGCCTTCGAGTCGGGGGCTAGAGCGGCCAGG
CCTCCGAGCCGGGTCGAGCCGAGGCTGGCGACGGCTGCGTCACGCGAGGGGGCGGGGCTG
CCACGGGCGGAGGTCGCAGCCGGAAGCGGAAGAGGCGCTCGGAGCGGGGAGTGGGGCCTA
GCTGCAGCCGGAGCCTGGGAGACGATGCATCACTGTAAGCGATACCGCTCCCCTGAACCA
GACCCGTACCTGAGCTACCGATGGAAGAGGAGGAGGTCCTACAGTCGGGAACATGAAGGG
AGACTGCGATACCCGTCCCGAAGGGAGCCTCCCCCACGAAGATCTCGGTCCAGAAGCCAT
GACCGCCTGCCCTACCAGAGGAGGTACCGGGAGCGCCGTGACAGCGATACATACCGGTGT
GAAGAGCGGAGCCCATCCTTTGGAGAGGACTACTATGGACCTTCACGTTCTCGTCATCGT
CGGCGATCGCGGGAGAGGGGGCCATACCGGACCCGCAAGCATGCCCACCACTGCCACAAA
CGCCGCACCAGGTCTTGTAGCAGCGCCTCCTCGAGAAGCCAACAGAGCAGTAAGCGCAGC
AGCCGGAGTGTGGAAGATGACAAGGAGGGTCACCTGGTGTGCCGGATCGGCGATTGGCTC
CAAGAGCGATATGAGATTGTGGGGAACCTGGGTGAAGGCACCTTTGGCAAGGTGGTGGAG
TGCTTGGACCATGCCAGAGGGAAGTCTCAGGTTGCCCTGAAGATCATCCGCAACGTGGGC
AAGTACCGGGAGGCTGCCCGGCTAGAAATCAACGTGCTCAAAAAAATCAAGGAGAAGGAC
AAAGAAAACAAGTTCCTGTGTGTCTTGATGTCTGACTGGTTCAACTTCCACGGTCACATG
TGCATCGCCTTTGAGCTCCTGGGCAAGAACACCTTTGAGTTCCTGAAGGAGAATAACTTC
CAGCCTTACCCCCTACCACATGTCCGGCACATGGCCTACCAGCTCTGCCACGCCCTTAGA
TTTCTGCATGAGAATCAGCTGACCCATACAGACTTGAAACCAGAGAACATCCTGTTTGTG
AATTCTGAGTTTGAAACCCTCTACAATGAGCACAAGAGCTGTGAGGAGAAGTCAGTGAAG
AACACCAGCATCCGAGTGGCTGACTTTGGCAGTGCCACATTTGACCATGAGCACCACACC
ACCATTGTGGCCACCCGTCACTATCGCCCGCCTGAGGTGATCCTTGAGCTGGGCTGGGCA
CAGCCCTGTGACGTCTGGAGCATTGGCTGCATTCTCTTTGAGTACTACCGGGGCTTCACA
CTCTTCCAGACCCACGAAAACCGAGAGCACCTGGTGATGATGGAGAAGATCCTAGGGCCC
ATCCCATCACACATGATCCACCGTACCAGGAAGCAGAAATATTTCTACAAAGGGGGCCTA
GTTTGGGATGAGAACAGCTCTGACGGCCGGTATGTGAAGGAGAACTGCAAACCTCTGAAG
AGTTACATGCTCCAAGACTCCCTGGAGCACGTGCAGCTGTTTGACCTGATGAGGAGGATG
TTAGAATTTGACCCTGCCCAGCGCATCACACTGGCCGAGGCCCTGCTGCACCCCTTCTTT
GCTGGCCTGACCCCTGAGGAGCGGTCCTTCCACACCAGCCGCAACCCAAGCAGATGA

Chromosome Location

15

Locus

15q24

External Identifiers

Resource	Link
UniProtKB ID	P49761
UniProtKB Entry Name	CLK3_HUMAN
GenBank Protein ID	632970
GenBank Gene ID	L29220
HGNC ID	HGNC:2071

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. Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. [Article]
3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
4. 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]
5. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. [Article]
6. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [Article]
7. 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]
8. 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]
9. 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]
10. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
11. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
12. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
13. Debdab M, Carreaux F, Renault S, Soundararajan M, Fedorov O, Filippakopoulos P, Lozach O, Babault L, Tahtouh T, Baratte B, Ogawa Y, Hagiwara M, Eisenreich A, Rauch U, Knapp S, Meijer L, Bazureau JP: Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. J Med Chem. 2011 Jun 23;54(12):4172-86. doi: 10.1021/jm200274d. Epub 2011 May 26. [Article]
14. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB07664	K-00546	experimental	unknown		Details
DB08691	ethyl 3-[(E)-2-amino-1-cyanoethenyl]-6,7-dichloro-1-methyl-1H-indole-2-carboxylate	experimental	unknown		Details
DB12010	Fostamatinib	approved, investigational	unknown	inhibitor	Details